Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes, CV outcomes, rosiglitazone, Type II diabetes, sulfonylurea, RECORD, metformin
Brief summary
This study is a phase 3b, multicentre, randomised, open label, parallel group study. A 4-week run-in period will be followed by a median of 6 years of treatment with study medication in addition to continuation of background glucose lowering therapy. Patients inadequately controlled on background metformin will be randomised to receive, in addition to metformin, either rosiglitazone or a sulfonylurea(glibenclamide, gliclazide or glimepiride) in a ratio of 1:1. Patients inadequately controlled on background SU will be randomised to receive, in addition to SU, either rosiglitazone or metformin in a ratio of 1:1. Equal numbers of patients receiving background metformin and SU at entry will be entered into the study.
Detailed description
A RECORD follow-up study is being performed to monitor the incidence of cancer and bone fractures in RECORD patients for a period of 4 years after the end of the main RECORD study (2008 - 2012).
Interventions
DRUGRosiglitazone
Rosiglitazone maximum 8 mg per day
DRUGSulfonylurea
Sulfonylurea (SU) maximum permitted daily dose
DRUGMetformin
Metformin maximum permitted daily dose .
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type II diabetes mellitus as defined by 1999 World Health Organisation criteria. * Glycated haemoglobin (HbA1c) \>7.0 % to = 9.0 % at visit 1. * Use of an oral glucose lowering agent for a minimum of 6 months prior to screening and unchanged for 2 months prior to screening. * Body mass index \>25.0 kg/m2.
Exclusion criteria
* Patients receiving any other glucose lowering therapy which is not metformin or a sulfonylurea. * Patients with systolic blood pressure \>180 mmHg or diastolic blood pressure \>105 mmHg. * Patients who have required the use of insulin for glycaemic control at any time in the past. * Hospitalisation for any major cardiovascular event in the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events | Baseline through End of Study (up to 7.5 years) | The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded. |
| Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause | Baseline through End of Study (up to 7.5 years) | All deaths identified during the original record study and discovered after the re-adjudication efforts began were included. |
| Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin. |
| Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury. |
| Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as unknown deaths, but were counted as CV deaths for the analysis of this endpoint. |
| Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths. |
| Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme \>= 2x the ULN or CK \> 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI. |
| Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. |
| Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke. |
| Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions | Baseline through End of Study (up to 7.5 years) | The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable. |
| Number of Participants With Cardiovascular Events and All-cause Deaths | Baseline through End of Study (up to 7.5 years) | Composites of participants with first cardiovascular (CV) hospitalisations and CV death or all-cause death and individual first events of acute myocardial infarction (MI) , stroke, congestive heart failure (CHF), CV death, and all-cause death. |
| Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Baseline through End of Study (up to 7.5 years) | The total number of events for individual components of cardiovascular (CV) hospitalisations and cardiovascular deaths were recorded. MI, myocardial infarction. |
| Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum | Baseline through End of Study (up to 7.5 years) | Participants with first cardiovascular death (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) were recorded by study stratum. |
| Number of Participants With CV/Microvascular Events | Baseline through End of Study (up to 7.5 years) | The number of participants with first cardiovascular or microvascular events (renal, foot, eye) were recorded. |
| Number of Participants With Glycaemic Failure Events | Baseline through to end of randomised dual therapy | Failure of glycaemic control was defined as two consecutive HbA1c values of ≥8.5 percent, or HbA1c ≥8.5percent at a single visit, after which the subject was either moved to the post-randomised treatment phase or triple therapy was started. |
| Number of Participants With Addition of Third Oral Agent/Switch to Insulin | Baseline through End of Study (up to 7.5 years) | The number of participants with addition of a third oral agent or switch to insulin from randomised dual combination treatment were recorded. |
| The Number of Participants Starting Insulin at Any Time During the Study | Baseline through End of Study (up to 7.5 years) | The number of participants starting insulin at any time during the study was recorded. |
| Model Adjusted Change From Baseline in HbA1c at Month 60 | Baseline and Month 60 of randomised dual therapy treatment period | Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value. |
| Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment period | Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in fasting plasma glucose was calculated as the value at Month 60 minus the Baseline value. |
| Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment period | Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in insulin and pro-insulin was calculated as the value at Month 60 minus the Baseline value. |
| Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment period | Number of responders, i.e., participants meeting glycaemic targets (HbA1c less than or equal to 7 percent, FPG less than or equal to 7 mmol/L) |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in TC, LDL cholesterol, HDL cholesterol, triglycerides, and FFAs was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment period | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in TC:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment period | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in Apo-B was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in urinary albumin creatinine ratio was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Change From Baseline in Body Weight at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in body weight was calculated as the value at Month 60 minus the Baseline value. |
| Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in alanine aminotransferase was calculated as the value at Month 60 minus the Baseline value. |
| Model Adjusted Change From Baseline in Waist Circumference at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in waist circumference was calculated as the value at Month 60 minus the Baseline value. |
| Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | Model adjusted (adjusted for any imbalances in the baseline values between within treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value. |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in C-Reactive Protein was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in fibrinogen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60 | Baseline to Month 60 of the randomised dual therapy treatment phase | The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in plasminogen activator inhibitor-1 (PAI-1) antigen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]). |
| Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. |
| Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. |
| Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. |
| Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable. |
| Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable. |
| Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. |
| Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. |
| Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant. |
| Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant. |
| Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown). |
| Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) | The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown). |
Countries
Australia, Belgium, Bulgaria, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Netherlands, New Zealand, Poland, Romania, Russia, Slovakia, Spain, Sweden, Ukraine, United Kingdom
Participant flow
Recruitment details
The RECORD study ran from April 2001 through December 2008. Results are presented in the non-re-adjudicated outcome measures (OMs). An independent patient-level re-adjudication of mortality, non-fatal myocardial infarction, and non-fatal stroke began on January 2011 and ran through March 2012. The results are presented in the re-adjudicated OMs.
Pre-assignment details
The RECORD observational follow-up (OFU) started at the end of the RECORD study and ran through December 2012. OFU was designed to collect cancer and bone fracture data. Participants were not provided with study medication in the OFU. Data are presented for the entire study (RECORD + OBF) and for OFU alone in the observational OMs.
Participants by arm
| Arm | Count |
|---|---|
| RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent. | 1,117 |
| SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. | 1,105 |
| RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent. | 1,103 |
| MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent. | 1,122 |
| Total | 4,447 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Main Study | Adverse Event | 5 | 8 | 10 | 11 | 0 | 0 |
| Main Study | Death | 57 | 67 | 54 | 72 | 0 | 0 |
| Main Study | Entry criteria violation | 0 | 0 | 1 | 1 | 0 | 0 |
| Main Study | Investigator refused to log temperature | 0 | 0 | 1 | 0 | 0 | 0 |
| Main Study | Lost to Follow-up | 29 | 29 | 25 | 26 | 0 | 0 |
| Main Study | Moved to survival status follow-up only | 27 | 25 | 32 | 36 | 0 | 0 |
| Main Study | Participant completed study at visit 27 | 1 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Participant did not take study drug | 0 | 0 | 1 | 0 | 0 | 0 |
| Main Study | Participant moved | 3 | 2 | 3 | 3 | 0 | 0 |
| Main Study | Personal reasons | 1 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Physician Decision | 2 | 2 | 1 | 1 | 0 | 0 |
| Main Study | Poor compliance | 3 | 2 | 2 | 1 | 0 | 0 |
| Main Study | Prohibited glucose lowering medication | 0 | 3 | 0 | 1 | 0 | 0 |
| Main Study | Reason unspecified | 0 | 0 | 1 | 0 | 0 | 0 |
| Main Study | Risk of heart failure | 0 | 1 | 0 | 0 | 0 | 0 |
| Main Study | Site closed | 4 | 4 | 4 | 8 | 0 | 0 |
| Main Study | Withdrawal by Subject | 46 | 56 | 72 | 70 | 0 | 0 |
| Observational Follow-up | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Observational Follow-up | Death | 0 | 0 | 0 | 0 | 78 | 70 |
| Observational Follow-up | Entered into Another Clinical Trial | 0 | 0 | 0 | 0 | 18 | 22 |
| Observational Follow-up | Lost to Follow-up | 0 | 0 | 0 | 0 | 25 | 27 |
| Observational Follow-up | Participant Moved | 0 | 0 | 0 | 0 | 0 | 1 |
| Observational Follow-up | Physician Decision | 0 | 0 | 0 | 0 | 8 | 8 |
| Observational Follow-up | Site Closed Early | 0 | 0 | 0 | 0 | 6 | 7 |
| Observational Follow-up | Unknown; Reason Not Provided | 0 | 0 | 0 | 0 | 1 | 1 |
| Observational Follow-up | Withdrawal by Subject | 0 | 0 | 0 | 0 | 12 | 12 |
Baseline characteristics
| Characteristic | RSG in Addition to Background MET | SU in Addition to Background MET | RSG in Addition to Background SU | MET in Addition to Background SU | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.0 years STANDARD_DEVIATION 8.02 | 57.2 years STANDARD_DEVIATION 8.14 | 59.8 years STANDARD_DEVIATION 8.26 | 59.7 years STANDARD_DEVIATION 8.23 | 58.4 years STANDARD_DEVIATION 8.27 |
| Race/Ethnicity, Customized Aboriginal | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized African | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 1 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Black | 3 participants | 6 participants | 2 participants | 3 participants | 14 participants |
| Race/Ethnicity, Customized Egyptian | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Gipsy | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Indian | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Maori | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Middle East Hible | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Oriental | 4 participants | 2 participants | 5 participants | 7 participants | 18 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Polynesian | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Sri Lankan | 0 participants | 2 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Tahitian | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 1105 participants | 1087 participants | 1095 participants | 1112 participants | 4399 participants |
| Sex: Female, Male Female | 516 Participants | 521 Participants | 562 Participants | 554 Participants | 2153 Participants |
| Sex: Female, Male Male | 601 Participants | 584 Participants | 541 Participants | 568 Participants | 2294 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1,117 / 1,117 | 1,105 / 1,105 | 1,103 / 1,103 | 1,122 / 1,122 | 0 / 1,280 | 0 / 1,250 |
| serious Total, serious adverse events | 424 / 1,117 | 428 / 1,105 | 427 / 1,103 | 431 / 1,122 | 99 / 1,280 | 76 / 1,250 |
Outcome results
Primary
Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions
IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions | 181 participants |
| Combined MET/SU | Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions | 188 participants |
95% CI: [0.78, 1.17]
Primary
Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions | 50 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions | 63 participants |
95% CI: [0.54, 1.14]
Primary
Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause
All deaths identified during the original record study and discovered after the re-adjudication efforts began were included.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause | 139 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause | 160 participants |
95% CI: [0.68, 1.08]
Primary
Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions
The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions | 88 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions | 96 participants |
95% CI: [0.68, 1.21]
Primary
Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions
The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as unknown deaths, but were counted as CV deaths for the analysis of this endpoint.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions | 88 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions | 96 participants |
95% CI: [0.68, 1.21]
Primary
Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions
Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions | 186 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions | 191 participants |
95% CI: [0.79, 1.18]
Primary
Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions | 72 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions | 62 participants |
95% CI: [0.82, 1.62]
Primary
Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme \>= 2x the ULN or CK \> 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions | 68 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions | 60 participants |
95% CI: [0.8, 1.59]
Primary
Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions | 53 participants |
| Combined MET/SU | Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions | 64 participants |
95% CI: [0.57, 1.18]
Primary
Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events
The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events | 321 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events | 323 participants |
95% CI: [0.85, 1.16]
Secondary
Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in alanine aminotransferase was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Combined RSG | Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 | -37.43 U/L (Units/Liter) |
| Combined MET/SU | Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 | -21.73 U/L (Units/Liter) |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 | -30.17 U/L (Units/Liter) |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 | -24.00 U/L (Units/Liter) |
Secondary
Model Adjusted Change From Baseline in Body Weight at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in body weight was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined RSG | Model Adjusted Change From Baseline in Body Weight at Month 60 | 3.93 kilograms | Standard Error 0.263 |
| Combined MET/SU | Model Adjusted Change From Baseline in Body Weight at Month 60 | -0.54 kilograms | Standard Error 0.192 |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in Body Weight at Month 60 | 4.72 kilograms | Standard Error 0.235 |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in Body Weight at Month 60 | -2.16 kilograms | Standard Error 0.179 |
Secondary
Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in fasting plasma glucose was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline to Month 60 of the randomised dual therapy treatment period
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined RSG | Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60 | -1.38 mmol/L (millimoles/Liter) | Standard Error 0.073 |
| Combined MET/SU | Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60 | -0.29 mmol/L (millimoles/Liter) | Standard Error 0.09 |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60 | -2.00 mmol/L (millimoles/Liter) | Standard Error 0.085 |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60 | -0.94 mmol/L (millimoles/Liter) | Standard Error 0.094 |
Secondary
Model Adjusted Change From Baseline in HbA1c at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline and Month 60 of randomised dual therapy treatment period
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined RSG | Model Adjusted Change From Baseline in HbA1c at Month 60 | -0.14 Percent | Standard Error 0.035 |
| Combined MET/SU | Model Adjusted Change From Baseline in HbA1c at Month 60 | 0.17 Percent | Standard Error 0.042 |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in HbA1c at Month 60 | -0.24 Percent | Standard Error 0.039 |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in HbA1c at Month 60 | -0.10 Percent | Standard Error 0.039 |
Secondary
Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined RSG | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | SBP | -1.9 mmHg (millimeters of mercury) | Standard Error 0.54 |
| Combined RSG | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | DBP | -3.6 mmHg (millimeters of mercury) | Standard Error 0.34 |
| Combined MET/SU | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | DBP | -3.4 mmHg (millimeters of mercury) | Standard Error 0.29 |
| Combined MET/SU | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | SBP | -2.2 mmHg (millimeters of mercury) | Standard Error 0.52 |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | SBP | -2.3 mmHg (millimeters of mercury) | Standard Error 0.52 |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | DBP | -3.6 mmHg (millimeters of mercury) | Standard Error 0.31 |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | SBP | -0.6 mmHg (millimeters of mercury) | Standard Error 0.53 |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 | DBP | -2.3 mmHg (millimeters of mercury) | Standard Error 0.31 |
Secondary
Model Adjusted Change From Baseline in Waist Circumference at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in waist circumference was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined RSG | Model Adjusted Change From Baseline in Waist Circumference at Month 60 | 2.70 cm (centimeters) | Standard Error 0.266 |
| Combined MET/SU | Model Adjusted Change From Baseline in Waist Circumference at Month 60 | 0.65 cm (centimeters) | Standard Error 0.214 |
| RSG in Addition to Background SU | Model Adjusted Change From Baseline in Waist Circumference at Month 60 | 3.00 cm (centimeters) | Standard Error 0.263 |
| MET in Addition to Background SU | Model Adjusted Change From Baseline in Waist Circumference at Month 60 | -0.60 cm (centimeters) | Standard Error 0.215 |
Secondary
Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60
Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in insulin and pro-insulin was calculated as the value at Month 60 minus the Baseline value.
Time frame: Baseline to Month 60 of the randomised dual therapy treatment period
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined RSG | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Insulin, Adjusted Change from Baseline | -18.6 picamoles/liter (pmol/L) | Standard Error 1.01 |
| Combined RSG | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Pro-insulin, Adjusted Change from Baseline | -2.4 picamoles/liter (pmol/L) | Standard Error 0.26 |
| Combined MET/SU | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Pro-insulin, Adjusted Change from Baseline | 4.2 picamoles/liter (pmol/L) | Standard Error 0.43 |
| Combined MET/SU | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Insulin, Adjusted Change from Baseline | 3.7 picamoles/liter (pmol/L) | Standard Error 1.77 |
| RSG in Addition to Background SU | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Insulin, Adjusted Change from Baseline | -16.9 picamoles/liter (pmol/L) | Standard Error 1.65 |
| RSG in Addition to Background SU | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Pro-insulin, Adjusted Change from Baseline | -3.2 picamoles/liter (pmol/L) | Standard Error 0.48 |
| MET in Addition to Background SU | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Insulin, Adjusted Change from Baseline | -12.1 picamoles/liter (pmol/L) | Standard Error 1.91 |
| MET in Addition to Background SU | Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 | Pro-insulin, Adjusted Change from Baseline | -3.0 picamoles/liter (pmol/L) | Standard Error 0.37 |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in Apo-B was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment period
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60 | -13.77 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60 | -11.63 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60 | -9.68 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60 | -12.09 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in C-Reactive Protein was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60 | -57.40 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60 | -28.92 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60 | -56.50 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60 | -36.29 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in fibrinogen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60 | 2.12 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60 | 5.74 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60 | -0.23 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60 | 3.14 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in plasminogen activator inhibitor-1 (PAI-1) antigen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60 | -9.85 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60 | 15.01 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60 | -7.79 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60 | -0.64 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in TC:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment period
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | Total Cholesterol: HDL Cholesterol Ratio | -14.20 percent change |
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | LDL Cholesterol: HDL-Cholesterol Ratio | -20.89 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | LDL Cholesterol: HDL-Cholesterol Ratio | -20.04 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | Total Cholesterol: HDL Cholesterol Ratio | -11.33 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | Total Cholesterol: HDL Cholesterol Ratio | -9.93 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | LDL Cholesterol: HDL-Cholesterol Ratio | -15.85 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | Total Cholesterol: HDL Cholesterol Ratio | -15.01 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 | LDL Cholesterol: HDL-Cholesterol Ratio | -22.53 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in TC, LDL cholesterol, HDL cholesterol, triglycerides, and FFAs was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Triglycerides | -7.97 percent change |
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | HDL-cholesterol | 9.95 percent change |
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Free fatty acids | -16.46 percent change |
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | LDL-cholesterol | -12.70 percent change |
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Total cholesterol | -5.49 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | LDL-cholesterol | -17.68 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Triglycerides | -1.95 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Free fatty acids | 2.79 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | HDL-cholesterol | 2.57 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Total cholesterol | -9.09 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | LDL-cholesterol | -8.99 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Total cholesterol | -2.91 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | HDL-cholesterol | 7.73 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Triglycerides | -2.68 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Free fatty acids | -11.58 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Triglycerides | -2.50 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | HDL-cholesterol | 6.14 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Total cholesterol | -9.68 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | LDL-cholesterol | -17.80 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 | Free fatty acids | 4.47 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in urinary albumin creatinine ratio was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60 | 8.31 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60 | 15.17 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60 | -3.43 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60 | 11.91 percent change |
Secondary
Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60
The model adjusted (adjusted for any imbalances in the baseline \[BL\] values between within stratum treatment groups) ratio to BL in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100\*\[GM\^-1\]).
Time frame: Baseline to Month 60 of the randomised dual therapy treatment phase
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Beta cell function | 20.54 percent change |
| Combined RSG | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Insulin sensitivity | 42.57 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Insulin sensitivity | -3.45 percent change |
| Combined MET/SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Beta cell function | 19.28 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Beta cell function | 32.35 percent change |
| RSG in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Insulin sensitivity | 42.07 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Beta cell function | 12.43 percent change |
| MET in Addition to Background SU | Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 | Insulin sensitivity | 23.90 percent change |
Secondary
Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Number of bone fracture events | 299 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Unknown | 7 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Normal healing with standard management | 250 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Complication | 14 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Additional therapeutic measures required | 16 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Data unavailable | 12 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Additional therapeutic measures required | 9 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Number of bone fracture events | 174 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Complication | 13 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Unknown | 5 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Data unavailable | 5 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined | Normal healing with standard management | 142 bone fracture events |
Secondary
Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Number of bone fracture events | 70 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Unknown | 1 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Normal healing with standard management | 51 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Complication | 7 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Additional therapeutic measures required | 3 bone fracture events |
| Combined RSG | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Data unavailable | 8 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Additional therapeutic measures required | 2 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Number of bone fracture events | 41 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Complication | 4 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Unknown | 1 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Data unavailable | 1 bone fracture events |
| Combined MET/SU | Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up | Normal healing with standard management | 33 bone fracture events |
Secondary
Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60
Number of responders, i.e., participants meeting glycaemic targets (HbA1c less than or equal to 7 percent, FPG less than or equal to 7 mmol/L)
Time frame: Baseline to Month 60 of the randomised dual therapy treatment period
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | HbA1c Responders | 265 participants |
| Combined RSG | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | FPG Responders | 300 participants |
| Combined MET/SU | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | FPG Responders | 180 participants |
| Combined MET/SU | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | HbA1c Responders | 208 participants |
| RSG in Addition to Background SU | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | HbA1c Responders | 235 participants |
| RSG in Addition to Background SU | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | FPG Responders | 257 participants |
| MET in Addition to Background SU | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | HbA1c Responders | 180 participants |
| MET in Addition to Background SU | Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 | FPG Responders | 154 participants |
Secondary
Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Gall bladder/biliary | 4 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any gastrointestinal event | 25 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Pancreatic | 4 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Colon/rectal | 6 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Gastric | 7 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Liver | 4 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any cancer-related death | 59 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Gastrointestinal event; not specified | 0 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any genitourinary event | 6 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Renal | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Uterine | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Prostate | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Bladder | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Ovarian | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Lung | 13 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any hematologic event | 4 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Skin (melanoma) | 3 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Skin (non-melanomatous) | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Metastases | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Breast | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Head and neck | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any neurologic event | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Endocrine | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Not specified | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Endocrine | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any cancer-related death | 72 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Bladder | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any gastrointestinal event | 34 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Metastases | 4 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Pancreatic | 12 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Ovarian | 2 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Colon/rectal | 11 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any neurologic event | 2 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Gastric | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Lung | 11 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Liver | 4 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Breast | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Gall bladder/biliary | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any hematologic event | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Gastrointestinal event; not specified | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Not specified | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Any genitourinary event | 15 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Skin (melanoma) | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Renal | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Head and neck | 2 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Uterine | 5 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Skin (non-melanomatous) | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined | Prostate | 2 participants |
Secondary
Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Gall bladder/biliary | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any gastrointestinal event | 10 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Pancreatic | 3 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Colon/rectal | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Gastric | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Liver | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any cancer-related death | 25 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Gastrointestinal event; not specified | 0 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any genitourinary event | 2 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Renal | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Uterine | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Prostate | 0 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Bladder | 0 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Ovarian | 0 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Lung | 4 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any hematologic event | 4 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Skin (melanoma) | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Skin (non-melanomatous) | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Metastases | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Breast | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Head and neck | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any neurologic event | 1 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Endocrine | 0 participants |
| Combined RSG | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Not specified | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Endocrine | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any cancer-related death | 24 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Bladder | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any gastrointestinal event | 14 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Metastases | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Pancreatic | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Ovarian | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Colon/rectal | 6 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any neurologic event | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Gastric | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Lung | 5 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Liver | 2 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Breast | 3 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Gall bladder/biliary | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any hematologic event | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Gastrointestinal event; not specified | 1 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Not specified | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Any genitourinary event | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Skin (melanoma) | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Renal | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Head and neck | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Uterine | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Skin (non-melanomatous) | 0 participants |
| Combined MET/SU | Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up | Prostate | 0 participants |
Secondary
Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | Overall, n=2220, 2227 | 238 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | Male, n=1142, 1152 | 82 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | Female, n=1078, 1075 | 156 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | Overall, n=2220, 2227 | 151 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | Male, n=1142, 1152 | 60 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined | Female, n=1078, 1075 | 91 participants |
Secondary
Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | Overall, n=1280, 1250 | 64 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | Male, n=665, 635 | 25 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | Female, n=615, 615 | 39 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | Overall, n=1280, 1250 | 37 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | Male, n=665, 635 | 11 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up | Female, n=615, 615 | 26 participants |
Secondary
Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined
The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Distal lower limb | 24 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Spinal | 7 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Upper limb | 41 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Pelvic | 0 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Femur/hip | 15 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Other | 7 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Any event | 81 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Other | 4 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Any event | 57 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Upper limb | 17 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Distal lower limb | 16 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Femur/hip | 11 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Spinal | 9 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined | Pelvic | 3 participants |
Secondary
Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up
The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Distal lower limb | 9 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Spinal | 2 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Upper limb | 17 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Pelvic | 0 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Femur/hip | 6 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Other | 2 participants |
| Combined RSG | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Any event | 35 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Other | 1 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Any event | 21 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Upper limb | 5 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Distal lower limb | 8 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Femur/hip | 4 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Spinal | 3 participants |
| Combined MET/SU | Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up | Pelvic | 1 participants |
Secondary
Number of Participants With Addition of Third Oral Agent/Switch to Insulin
The number of participants with addition of a third oral agent or switch to insulin from randomised dual combination treatment were recorded.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | Participants with an event | 295 participants |
| Combined RSG | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Insulin | 38 participants |
| Combined RSG | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Triple Therapy | 257 participants |
| Combined MET/SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | Participants with an event | 183 participants |
| Combined MET/SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Insulin | 176 participants |
| Combined MET/SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Triple Therapy | 7 participants |
| RSG in Addition to Background SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Triple Therapy | 296 participants |
| RSG in Addition to Background SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | Participants with an event | 344 participants |
| RSG in Addition to Background SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Insulin | 49 participants |
| MET in Addition to Background SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | Participants with an event | 171 participants |
| MET in Addition to Background SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Insulin | 165 participants |
| MET in Addition to Background SU | Number of Participants With Addition of Third Oral Agent/Switch to Insulin | First Event - Triple Therapy | 6 participants |
Secondary
Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined | 0 participants |
| Combined MET/SU | Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined | 0 participants |
Secondary
Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Any event | 238 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Non-traumatic event | 113 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Traumatic event | 110 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Pathologic | 1 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Unknown | 20 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Data unavailable | 9 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Unknown | 19 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Any event | 151 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Pathologic | 4 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Non-traumatic event | 55 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Data unavailable | 3 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined | Traumatic event | 77 participants |
Secondary
Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Any event | 64 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Non-traumatic event, | 36 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Traumatic event | 24 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Pathologic | 1 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Unknown | 1 participants |
| Combined RSG | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Data unavailable | 3 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Unknown | 4 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Any event | 37 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Pathologic | 2 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Non-traumatic event, | 14 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Data unavailable | 1 participants |
| Combined MET/SU | Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up | Traumatic event | 17 participants |
Secondary
Number of Participants With Cardiovascular Events and All-cause Deaths
Composites of participants with first cardiovascular (CV) hospitalisations and CV death or all-cause death and individual first events of acute myocardial infarction (MI) , stroke, congestive heart failure (CHF), CV death, and all-cause death.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | CV death, acute MI, stroke | 154 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | CV death, acute MI, stroke, unstable angina | 171 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | CV death, acute MI, stroke, unstable angina, CHF | 204 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | All-cause death,acuteMI,stroke,unstable angina,CHF | 251 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | Acute MI (fatal or non-fatal) | 64 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | Stroke (fatal or non-fatal) | 46 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | CHF (fatal or non-fatal) | 61 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | Death from CV causes | 60 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | Death (all cause) during CV follow-up | 111 participants |
| Combined RSG | Number of Participants With Cardiovascular Events and All-cause Deaths | Death (all-cause) including survival status | 136 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | Death from CV causes | 71 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | CV death, acute MI, stroke | 165 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | Stroke (fatal or non-fatal) | 63 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | CV death, acute MI, stroke, unstable angina | 184 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | Death (all-cause) including survival status | 157 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | CV death, acute MI, stroke, unstable angina, CHF | 206 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | CHF (fatal or non-fatal) | 29 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | All-cause death,acuteMI,stroke,unstable angina,CHF | 268 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | Death (all cause) during CV follow-up | 139 participants |
| Combined MET/SU | Number of Participants With Cardiovascular Events and All-cause Deaths | Acute MI (fatal or non-fatal) | 56 participants |
Secondary
Number of Participants With CV/Microvascular Events
The number of participants with first cardiovascular or microvascular events (renal, foot, eye) were recorded.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With CV/Microvascular Events | Participants with any microvascular event | 59 participants |
| Combined RSG | Number of Participants With CV/Microvascular Events | Participants with any foot event | 19 participants |
| Combined RSG | Number of Participants With CV/Microvascular Events | Participants with any eye event | 42 participants |
| Combined RSG | Number of Participants With CV/Microvascular Events | Participants with any renal event | 0 participants |
| Combined RSG | Number of Participants With CV/Microvascular Events | Participants with a CV/Microvascular event | 363 participants |
| Combined MET/SU | Number of Participants With CV/Microvascular Events | Participants with any renal event | 0 participants |
| Combined MET/SU | Number of Participants With CV/Microvascular Events | Participants with a CV/Microvascular event | 385 participants |
| Combined MET/SU | Number of Participants With CV/Microvascular Events | Participants with any microvascular event | 78 participants |
| Combined MET/SU | Number of Participants With CV/Microvascular Events | Participants with any eye event | 52 participants |
| Combined MET/SU | Number of Participants With CV/Microvascular Events | Participants with any foot event | 28 participants |
Secondary
Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum
Participants with first cardiovascular death (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) were recorded by study stratum.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum | 158 partcipants |
| Combined MET/SU | Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum | 154 partcipants |
| RSG in Addition to Background SU | Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum | 163 partcipants |
| MET in Addition to Background SU | Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum | 169 partcipants |
Secondary
Number of Participants With Glycaemic Failure Events
Failure of glycaemic control was defined as two consecutive HbA1c values of ≥8.5 percent, or HbA1c ≥8.5percent at a single visit, after which the subject was either moved to the post-randomised treatment phase or triple therapy was started.
Time frame: Baseline through to end of randomised dual therapy
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | Number of Participants With Glycaemic Failure Events | 281 participants |
| Combined MET/SU | Number of Participants With Glycaemic Failure Events | 451 participants |
| RSG in Addition to Background SU | Number of Participants With Glycaemic Failure Events | 365 participants |
| MET in Addition to Background SU | Number of Participants With Glycaemic Failure Events | 424 participants |
Secondary
Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown).
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Any H/UA/FF event, male, n=1142, 1152 | 28 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | High morbidity fractures, female, n=1078, 1075 | 5 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | High morbidity fractures, overall, n=2220, 2227 | 5 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Non-high morbidity fractures, overall, n=2220, 222 | 15 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Any H/UA/FF event, female, n=1078, 1075 | 58 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Non-high morbidity fractures, male, n=1142, 1152 | 2 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | High morbidity fractures, male, n=1142, 1152 | 0 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Non-high morbidity fractures, female, n=1078, 1075 | 13 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Any H/UA/FF event, overall, n=2220, 2227 | 86 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Non-high morbidity fractures, female, n=1078, 1075 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Any H/UA/FF event, overall, n=2220, 2227 | 46 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Any H/UA/FF event, male, n=1142, 1152 | 15 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Any H/UA/FF event, female, n=1078, 1075 | 31 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | High morbidity fractures, overall, n=2220, 2227 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | High morbidity fractures, male, n=1142, 1152 | 0 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | High morbidity fractures, female, n=1078, 1075 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Non-high morbidity fractures, overall, n=2220, 222 | 4 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined | Non-high morbidity fractures, male, n=1142, 1152 | 3 participants |
Secondary
Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown).
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Pelvis, overall, n=2220, 2227 | 0 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any event, male, n=1142, 1152 | 10 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any event, female, n=1078, 1075 | 21 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Hip, overall, n=2220, 2227 | 9 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Hip, male, n=1142, 1152 | 0 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Hip, female, n=1078, 1075 | 9 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any event, overall, n=2220, 2227 | 31 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Pelvis, male, n=1142, 1152 | 0 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Pelvis, female, n=1078, 1075 | 0 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Upper leg, overall, n=2220, 2227 | 7 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Upper leg, male, n=1142, 1152 | 4 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Upper leg, female, n=1078, 1075 | 3 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any vertebral event, overall, n=2220, 2227 | 16 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any vertebral event, male, n=1142, 1152 | 6 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any vertebral event, female, n=1078, 1075 | 10 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Lumbar spine, overall, n=2220, 2227 | 10 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Lumbar spine, male, n=1142, 1152 | 5 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Lumbar spine, female, n=1078, 1075 | 5 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Thoracic spine, overall, n=2220, 2227 | 5 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Thoracic spine, male, n=1142, 1152 | 1 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Thoracic spine, female, n=1078, 1075 | 4 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Cervical spine, overall, n=2220, 2227 | 1 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Cervical spine, male, n=1142, 1152 | 0 participants |
| Combined RSG | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Cervical spine, female, n=1078, 1075 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Cervical spine, male, n=1142, 1152 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any event, overall, n=2220, 2227 | 31 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any vertebral event, overall, n=2220, 2227 | 13 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any event, male, n=1142, 1152 | 13 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Thoracic spine, overall, n=2220, 2227 | 8 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any event, female, n=1078, 1075 | 18 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any vertebral event, male, n=1142, 1152 | 8 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Hip, overall, n=2220, 2227 | 7 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Cervical spine, overall, n=2220, 2227 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Hip, male, n=1142, 1152 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Any vertebral event, female, n=1078, 1075 | 5 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Hip, female, n=1078, 1075 | 6 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Thoracic spine, male, n=1142, 1152 | 4 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Pelvis, overall, n=2220, 2227 | 5 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Lumbar spine, overall, n=2220, 2227 | 4 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Pelvis, male, n=1142, 1152 | 4 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Cervical spine, female, n=1078, 1075 | 0 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Pelvis, female, n=1078, 1075 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Lumbar spine, male, n=1142, 1152 | 3 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Upper leg, overall, n=2220, 2227 | 6 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Thoracic spine, female, n=1078, 1075 | 4 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Upper leg, male, n=1142, 1152 | 0 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Lumbar spine, female, n=1078, 1075 | 1 participants |
| Combined MET/SU | Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined | Upper leg, female, n=1078, 1075 | 6 participants |
Secondary
Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Femur/hip, any event, female; n=1078, 1075 | 12 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Distal lower limb, any event, overall; n=2220, 222 | 88 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Distal lower limb, any event, male; n=1142, 1152 | 31 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Distal lower limb, any event, female; n=1078, 1075 | 57 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Femur/hip, any event, overall; n=2220, 2227 | 16 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Femur/hip, any event, male; n=1142, 1152 | 4 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Upper limb, any event, female; n=1078, 1075 | 84 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Spinal, any event, overall; n=2220, 2227 | 18 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Spinal, any event, male; n=1142, 1152 | 7 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Spinal, any event, female; n=1078, 1075 | 11 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Pelvic, any event, overall; n=2220, 2227 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Pelvic, any event, male; n=1142, 1152 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Pelvic, any event, female; n=1078, 1075 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Unclassified, any event, overall; n=2220, 2227 | 1 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Unclassified, any event, male; n=1142, 1152 | 1 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Unclassified, any event, female; n=1078, 1075 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Other, any event, overall; n=2220, 2227 | 31 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Other, any event, male; n=1142, 1152 | 18 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Other, any event, female; n=1078, 1075 | 13 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Any event, overall; n=2220, 2227 | 238 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Any event, male; n=1142, 1152 | 82 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Any event, female; n=1078, 1075 | 156 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Upper limb, any event, overall; n=2220, 2227 | 116 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Upper limb, any event, male; n=1142, 1152 | 32 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Upper limb, any event, overall; n=2220, 2227 | 70 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Upper limb, any event, female; n=1078, 1075 | 48 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Pelvic, any event, female; n=1078, 1075 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Distal lower limb, any event, overall; n=2220, 222 | 40 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Other, any event, female; n=1078, 1075 | 10 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Distal lower limb, any event, male; n=1142, 1152 | 14 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Unclassified, any event, overall; n=2220, 2227 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Distal lower limb, any event, female; n=1078, 1075 | 26 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Any event, female; n=1078, 1075 | 91 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Femur/hip, any event, overall; n=2220, 2227 | 13 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Unclassified, any event, male; n=1142, 1152 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Femur/hip, any event, male; n=1142, 1152 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Any event, overall; n=2220, 2227 | 151 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Femur/hip, any event, female; n=1078, 1075 | 12 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Unclassified, any event, female; n=1078, 1075 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Spinal, any event, overall; n=2220, 2227 | 14 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Upper limb, any event, male; n=1142, 1152 | 22 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Spinal, any event, male; n=1142, 1152 | 9 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Other, any event, overall; n=2220, 2227 | 26 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Spinal, any event, female; n=1078, 1075 | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Any event, male; n=1142, 1152 | 60 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Pelvic, any event, overall; n=2220, 2227 | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Other, any event, male; n=1142, 1152 | 16 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined | Pelvic, any event, male; n=1142, 1152 | 4 participants |
Secondary
Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Distal lower limb, any event, overall; n=1280,1250 | 18 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Any event, male; n=665, 635 | 25 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Any event, female; n=615, 615 | 39 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Upper limb, any event, overall; n=1280, 1250 | 33 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Upper limb, any event, male; n=665, 635 | 10 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Upper limb, any event, female; n=615, 615 | 23 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Any event, overall; n=1280, 1250 | 64 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Distal lower limb, any event, male; n=665, 635 | 9 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Distal lower limb, any event, female; n=615, 615 | 9 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Femur/hip, any event, overall; n=1280, 1250 | 6 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Femur/hip, any event, male; n=665, 635 | 1 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Femur/hip, any event, female; n=615, 615 | 5 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Spinal, any event, overall; n=1280, 1250 | 4 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Spinal, any event, male; n=665, 635 | 1 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Spinal, any event, female; n=615, 615 | 3 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Pelvic, any event, overall; n=1280, 1250 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Pelvic, any event, male; n=665, 635 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Pelvic, any event, female; n=615, 615 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Unclassified, any event, overall; n=1280, 1250 | 1 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Unclassified, any event, male; n=665, 635 | 1 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Unclassified, any event, female; n=615, 615 | 0 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Other, any event, overall; n=1280, 1250 | 6 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Other, any event, male; n=665, 635 | 4 participants |
| Combined RSG | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Other, any event, female; n=615, 615 | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Other, any event, male; n=665, 635 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Any event, overall; n=1280, 1250 | 37 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Spinal, any event, overall; n=1280, 1250 | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Any event, male; n=665, 635 | 11 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Unclassified, any event, overall; n=1280, 1250 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Any event, female; n=615, 615 | 26 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Spinal, any event, male; n=665, 635 | 4 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Upper limb, any event, overall; n=1280, 1250 | 15 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Other, any event, overall; n=1280, 1250 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Upper limb, any event, male; n=665, 635 | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Spinal, any event, female; n=615, 615 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Upper limb, any event, female; n=615, 615 | 12 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Unclassified, any event, male; n=665, 635 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Distal lower limb, any event, overall; n=1280,1250 | 13 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Pelvic, any event, overall; n=1280, 1250 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Distal lower limb, any event, male; n=665, 635 | 4 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Other, any event, female; n=615, 615 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Distal lower limb, any event, female; n=615, 615 | 9 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Pelvic, any event, male; n=665, 635 | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Femur/hip, any event, overall; n=1280, 1250 | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Unclassified, any event, female; n=615, 615 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Femur/hip, any event, male; n=665, 635 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Pelvic, any event, female; n=615, 615 | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up | Femur/hip, any event, female; n=615, 615 | 5 participants |
Secondary
Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Any event | 99 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Ankle fracture | 6 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Prostate cancer | 7 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lung neoplasm malignant | 4 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Breast cancer | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Basal cell carcinoma | 4 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pancreatic carcinoma | 4 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Colon cancer | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Humerus fracture | 5 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Upper limb fracture | 5 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Malignant melanoma | 3 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Uterine cancer | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Gastric cancer | 4 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Wrist fracture | 4 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Hip fracture | 3 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Radius fracture | 3 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Forearm fracture | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Hepatic neoplasm malignant | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal cancer | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Renal cancer | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Foot fracture | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Renal cell carcinoma | 3 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Femur fracture | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Femoral neck fracture | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lumbar vertebral fracture | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to bone | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to liver | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Bladder cancer | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Fall | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to central nervous system | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rib fracture | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Squamous cell carcinoma | 2 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Acute myocardial infarction | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Brain neoplasm | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Gastric neoplasm | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to lung | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Patella fracture | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Death | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Abdominal pain | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Acute myeloid leukaemia | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Acute respiratory failure | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Anaemia | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Benign salivary gland neoplasm | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Biliary colic | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Biliary neoplasm | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Bone neoplasm malignant | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Bronchial carcinoma | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Cardiac failure acute | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Chest pain | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Chronic lymphocytic leukaemia | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Colon neoplasm | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Contusion | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Drowning | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Dysplasia | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Endometrial cancer stage I | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Leukaemia | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lower limb fracture | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lung squamous cell carcinoma stage unspecified | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lymphoma | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Malignant neoplasm of pleura | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to skin | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to testicle | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastatic renal cell carcinoma | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Oesophageal carcinoma | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Osteoarthritis | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pancreatic necrosis | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal cancer stage II | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Spinal fracture | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | T-cell lymphoma | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Urinary tract infection | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Uterine leiomyosarcoma | 1 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Biliary cancer metastatic | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Cervix carcinoma | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Chronic obstructive pulmonary disease | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Comminuted fracture | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Craniocerebral injury | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Gastrointestinal neoplasm | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Hepatic lesion | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Joint dislocation | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Laryngeal cancer | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lip neoplasm malignant stage unspecified | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lung neoplasm | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to lymph nodes | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastasis | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Musculoskeletal chest pain | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Myocardial infarction | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Non-Hodgkin's lymphoma | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pubis fracture | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pulmonary embolism | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal cancer recurrent | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal neoplasm | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Skin cancer | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Skin ulcer | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Small cell lung cancer stage unspecified | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Sternal fracture | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Subdural haemorrhage | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Sudden death | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Thoracic vertebral fracture | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Thyroid cancer | 0 participants |
| Combined RSG | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Vulval cancer | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pubis fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Any event | 76 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Colon neoplasm | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Ankle fracture | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Craniocerebral injury | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Prostate cancer | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Contusion | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lung neoplasm malignant | 4 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Thyroid cancer | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Breast cancer | 6 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Drowning | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Basal cell carcinoma | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Gastrointestinal neoplasm | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pancreatic carcinoma | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Dysplasia | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Colon cancer | 6 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pulmonary embolism | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Humerus fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Endometrial cancer stage I | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Upper limb fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Hepatic lesion | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Malignant melanoma | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Leukaemia | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Uterine cancer | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Sternal fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Gastric cancer | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lower limb fracture | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Wrist fracture | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Joint dislocation | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Hip fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lung squamous cell carcinoma stage unspecified | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Radius fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal cancer recurrent | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Forearm fracture | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lymphoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Hepatic neoplasm malignant | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Laryngeal cancer | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal cancer | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Malignant neoplasm of pleura | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Renal cancer | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Thoracic vertebral fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Foot fracture | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to skin | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Renal cell carcinoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lip neoplasm malignant stage unspecified | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Femur fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to testicle | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Femoral neck fracture | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal neoplasm | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lumbar vertebral fracture | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastatic renal cell carcinoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to bone | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Lung neoplasm | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to liver | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Oesophageal carcinoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Bladder cancer | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Subdural haemorrhage | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Fall | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Comminuted fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to central nervous system | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Osteoarthritis | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rib fracture | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to lymph nodes | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Squamous cell carcinoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Pancreatic necrosis | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Acute myocardial infarction | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Skin cancer | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Brain neoplasm | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Rectal cancer stage II | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Gastric neoplasm | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastasis | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Metastases to lung | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Spinal fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Patella fracture | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Vulval cancer | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Death | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | T-cell lymphoma | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Abdominal pain | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Musculoskeletal chest pain | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Acute myeloid leukaemia | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Urinary tract infection | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Acute respiratory failure | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Skin ulcer | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Anaemia | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Uterine leiomyosarcoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Benign salivary gland neoplasm | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Myocardial infarction | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Biliary colic | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Biliary cancer metastatic | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Biliary neoplasm | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Sudden death | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Bone neoplasm malignant | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Cervix carcinoma | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Bronchial carcinoma | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Non-Hodgkin's lymphoma | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Cardiac failure acute | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Chronic obstructive pulmonary disease | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Chest pain | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Small cell lung cancer stage unspecified | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up | Chronic lymphocytic leukaemia | 0 participants |
Secondary
Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined
The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Ovarian | 5 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Prostate | 22 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Renal | 12 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Uterine | 11 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Bladder | 8 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Vaginal/vulvar | 1 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Any genitourinary | 57 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Any gastrointestinal | 48 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Colon/rectal cancer | 22 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Colon | 14 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Gastric | 13 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Pancreatic | 5 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Liver | 4 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Gall bladder/biliary | 4 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Gastrointestinal; not specified | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Any hematologic | 12 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Lung | 19 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Skin (non-melanomatous) | 19 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Skin (melanomatous) | 6 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Metastases | 12 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Breast | 12 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Head and neck | 4 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Neurologic | 3 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Endocrine | 3 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Not specified | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Other | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Metastases | 18 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Any genitourinary | 57 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Gall bladder/biliary | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Prostate | 22 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Not specified | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Renal | 9 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Gastrointestinal; not specified | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Uterine | 16 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Breast | 23 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Bladder | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Any hematologic | 6 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Vaginal/vulvar | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Endocrine | 6 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Ovarian | 4 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Lung | 15 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Any gastrointestinal | 62 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Head and neck | 7 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Colon/rectal cancer | 30 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Skin (non-melanomatous) | 13 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Colon | 21 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Other | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Gastric | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Skin (melanomatous) | 4 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Pancreatic | 16 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Neurologic | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined | Liver | 5 participants |
Secondary
Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up
The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Ovarian | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Prostate | 7 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Renal | 5 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Uterine | 4 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Bladder | 2 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Vaginal/vulvar | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Any genitourinary | 18 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Any gastrointestinal | 17 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Colon/rectal cancer | 5 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Colon | 2 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Gastric | 5 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Pancreatic | 4 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Liver | 2 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Gall bladder/biliary | 1 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Gastrointestinal; not specified | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Any hematologic | 6 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Lung | 6 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Skin (non-melanomatous) | 6 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Skin (melanomatous) | 3 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Metastases | 3 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Breast | 2 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Not specified | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Head and neck | 2 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Neurologic | 1 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Endocrine | 0 participants |
| Combined RSG | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Other | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Metastases | 6 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Any genitourinary | 8 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Gall bladder/biliary | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Prostate | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Neurologic | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Renal | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Gastrointestinal; not specified | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Uterine | 4 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Other | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Bladder | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Any hematologic | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Vaginal/vulvar | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Breast | 7 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Ovarian | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Lung | 6 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Any gastrointestinal | 19 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Endocrine | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Colon/rectal cancer | 11 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Skin (non-melanomatous) | 5 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Colon | 7 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Head and neck | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Gastric | 1 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Skin (melanomatous) | 2 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Pancreatic | 3 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Not specified | 0 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up | Liver | 2 participants |
Secondary
Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)
Population: ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | All neoplasms/cancer (N/C) (benign/malignant) | 196 participants |
| Combined RSG | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | Malignant (Mal.) N/C | 179 participants |
| Combined RSG | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | Mal. N/C; excluding non-melanomatous skin cancers | 164 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | All neoplasms/cancer (N/C) (benign/malignant) | 215 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | Malignant (Mal.) N/C | 195 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined | Mal. N/C; excluding non-melanomatous skin cancers | 186 participants |
Secondary
Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up
The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)
Population: Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | All neoplasms/cancer (N/C) (benign/malignant) | 60 participants |
| Combined RSG | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | Malignant (Mal.) N/C | 59 participants |
| Combined RSG | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | Mal. N/C; excluding non-melanomatous skin cancers | 55 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | All neoplasms/cancer (N/C) (benign/malignant) | 51 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | Malignant (Mal.) N/C | 51 participants |
| Combined MET/SU | Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up | Mal. N/C; excluding non-melanomatous skin cancers | 46 participants |
Secondary
The Number of Participants Starting Insulin at Any Time During the Study
The number of participants starting insulin at any time during the study was recorded.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined RSG | The Number of Participants Starting Insulin at Any Time During the Study | 126 participants |
| Combined MET/SU | The Number of Participants Starting Insulin at Any Time During the Study | 276 participants |
| RSG in Addition to Background SU | The Number of Participants Starting Insulin at Any Time During the Study | 168 participants |
| MET in Addition to Background SU | The Number of Participants Starting Insulin at Any Time During the Study | 259 participants |
Secondary
Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths
The total number of events for individual components of cardiovascular (CV) hospitalisations and cardiovascular deaths were recorded. MI, myocardial infarction.
Time frame: Baseline through End of Study (up to 7.5 years)
Population: Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | CV deaths | 60 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death due to acute MI | 7 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death due to heart failure | 10 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Sudden death | 8 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death due to acute vascular events | 1 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Other CV mortality | 6 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death of presumed CV cause | 28 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Cardiovascular hospitalisation | 483 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for acute MI | 66 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for unstable angina | 28 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for congestive heart failure | 69 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for stroke | 51 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for transient ischaemic attack | 10 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for invasive CV procedure | 99 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for amputation of extremities | 6 Number of events |
| Combined RSG | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Other CV hospitalisations | 154 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Other CV hospitalisations | 153 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | CV deaths | 71 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for acute MI | 57 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death due to acute MI | 10 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for transient ischaemic attack | 10 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death due to heart failure | 2 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for unstable angina | 28 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Sudden death | 12 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for amputation of extremities | 23 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death due to acute vascular events | 10 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for congestive heart failure | 36 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Other CV mortality | 4 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for invasive CV procedure | 116 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Death of presumed CV cause | 33 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Hospitalisation for stroke | 67 Number of events |
| Combined MET/SU | Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths | Cardiovascular hospitalisation | 490 Number of events |