Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a clinical trial designed to assess the cardiovascular outcome of long-term treatment with sitagliptin used as part of usual care compared to usual care without sitagliptin in participants with type 2 diabetes mellitus (T2DM) having a history of cardiovascular (CV) disease and a hemoglobin A1c (HbA1c) of 6.5% to 8.0%. Primary hypothesis A is that sitagliptin, when used as part of usual care, is non-inferior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint of Major Adverse Cardiovascular Event (MACE) plus. If hypothesis A is satisfied: hypothesis B is that sitagliptin, when used as part of usual care, is superior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint.
Interventions
DRUGPlacebo
Placebo tablet matching the 50 mg or 100 mg sitagliptin tablet, orally, once daily.
DRUGSitagliptin
Sitagliptin, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily.
Sponsors
Duke Clinical Research Institute, Oxford Diabetes Trials Unit
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has T2DM * Has HbA1c between 6.5% (48 mmol/mol) and 8.0% (64 mmol/mol) on stable dose(s) of antihyperglycemic agent(s), including insulin * Has pre-existing cardiovascular disease
Exclusion criteria
* Has a history of type 1 diabetes mellitus or ketoacidosis. * Is not able to take sitagliptin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population) | Up to 5 years | Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization. |
| Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population) | Up to 5 years | Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Incidence of All-cause Mortality (Per Protocol Population) | Up to 5 years | Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause. |
| Percent Incidence of All-cause Mortality (Intent to Treat Population) | Up to 5 years | Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause. |
| Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population) | Up to 5 years | Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF. |
| Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population) | Up to 5 years | Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF. |
| Change From Baseline in Renal Function Over Time (Per Protocol Population) | Baseline and up to 5 years | Change in renal function based on estimated glomerular filtration rate \[eGFR\] using the Modification of Diet in Renal Disease \[MDRD\] method. |
| Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Baseline and up to 5 years | Change in renal function based on eGFR using the MDRD method. |
| Change From Baseline in HbA1c Over Time (Per Protocol Population) | Baseline and up to 4 years | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region. |
| Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population) | Up to 5 years | CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke. |
| Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Baseline and up to 5 years | Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value. |
| Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Baseline and up to 5 years | Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value. |
| Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population) | Up to 5 years | Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months. |
| Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population) | Up to 5 years | Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months. |
| Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population) | Up to 5 years | In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent \[AHA\] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.) |
| Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population) | Up to 5 years | In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.) |
| Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Baseline and up to 4 years | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region. |
| Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population) | Up to 5 years | CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke. |
Participant flow
Pre-assignment details
A total of 14,671 participants were randomized to treatment, provided consent and did not have any Good Clinical Practice (GCP) deviations.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years | 7,332 |
| Placebo Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years | 7,339 |
| Total | 14,671 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 61 | 71 |
| Overall Study | Withdrawal by Subject | 299 | 363 |
Baseline characteristics
| Characteristic | Total | Placebo | Sitagliptin |
|---|---|---|---|
| Age, Customized 85 years and over | 101 Participants | 55 Participants | 46 Participants |
| Age, Customized Adults 18 - 64 years | 65.5 Participants 8 | 3301 Participants 8 | 3315 Participants 7.9 |
| Age, Customized From 65 - 84 years | 7634 Participants | 3821 Participants | 3813 Participants |
| Age, Customized Unknown age | 320 Participants | 162 Participants | 158 Participants |
| Estimated Glomerular Filtration Rate (eGFR) | 74.9 mL/min/1.73 m^2 STANDARD_DEVIATION 21.1 | 74.9 mL/min/1.73 m^2 STANDARD_DEVIATION 20.9 | 74.9 mL/min/1.73 m^2 STANDARD_DEVIATION 21.3 |
| Hemoglobin A1c (HbA1c) | 7.2 Percentage of HbA1c STANDARD_DEVIATION 0.5 | 7.2 Percentage of HbA1c STANDARD_DEVIATION 0.5 | 7.2 Percentage of HbA1c STANDARD_DEVIATION 0.5 |
| Sex: Female, Male Female | 4297 Participants | 2163 Participants | 2134 Participants |
| Sex: Female, Male Male | 10374 Participants | 5176 Participants | 5198 Participants |
| Urine albumin creatinine ratio | 8.5 g/mol Creatinine STANDARD_DEVIATION 36.7 | 8.4 g/mol Creatinine STANDARD_DEVIATION 36 | 8.6 g/mol Creatinine STANDARD_DEVIATION 37.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 7,266 | 0 / 7,274 |
| serious Total, serious adverse events | 928 / 7,266 | 909 / 7,274 |
Outcome results
Primary
Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)
Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
Time frame: Up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population) | 9.6 Percentage of participants |
| Placebo | Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population) | 9.6 Percentage of participants |
p-value: <0.00195% CI: [0.88, 1.09]Cox proportional hazards model
Primary
Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)
Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
Time frame: Up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population) | 11.4 Percentage of participants |
| Placebo | Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population) | 11.6 Percentage of participants |
p-value: <0.00195% CI: [0.89, 1.08]Cox proportional hazards model
Secondary
Change From Baseline in HbA1c Over Time (Intent to Treat Population)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.
Time frame: Baseline and up to 4 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation. Number of participants analyzed consists of those participants in the intent to treat population with a baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 12: Sitagliptin, n= 6448; Placebo, n= 6384 | -0.2 Percentage of HbA1c | Standard Deviation 1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 36: Sitagliptin, n= 3521; Placebo, n= 3439 | -0.1 Percentage of HbA1c | Standard Deviation 1.1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 8: Sitagliptin, n= 6478; Placebo, n= 6414 | -0.2 Percentage of HbA1c | Standard Deviation 0.9 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 48: Sitagliptin, n= 1432; Placebo, n= 1383 | 0.0 Percentage of HbA1c | Standard Deviation 1.1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 24: Sitagliptin, n= 6105; Placebo, n= 5975 | -0.1 Percentage of HbA1c | Standard Deviation 1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 60: Sitagliptin, n= 123; Placebo, n= 128 | 0.0 Percentage of HbA1c | Standard Deviation 1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 4: Sitagliptin, n= 6772; Placebo, n= 6738 | -0.3 Percentage of HbA1c | Standard Deviation 0.8 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 60: Sitagliptin, n= 123; Placebo, n= 128 | 0.0 Percentage of HbA1c | Standard Deviation 1 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 4: Sitagliptin, n= 6772; Placebo, n= 6738 | 0.1 Percentage of HbA1c | Standard Deviation 0.9 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 8: Sitagliptin, n= 6478; Placebo, n= 6414 | 0.1 Percentage of HbA1c | Standard Deviation 1 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 12: Sitagliptin, n= 6448; Placebo, n= 6384 | 0.1 Percentage of HbA1c | Standard Deviation 1 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 24: Sitagliptin, n= 6105; Placebo, n= 5975 | 0.1 Percentage of HbA1c | Standard Deviation 1.1 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 36: Sitagliptin, n= 3521; Placebo, n= 3439 | 0.1 Percentage of HbA1c | Standard Deviation 1.1 |
| Placebo | Change From Baseline in HbA1c Over Time (Intent to Treat Population) | Month 48: Sitagliptin, n= 1432; Placebo, n= 1383 | 0.1 Percentage of HbA1c | Standard Deviation 1.2 |
Secondary
Change From Baseline in HbA1c Over Time (Per Protocol Population)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.
Time frame: Baseline and up to 4 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data. Number of participants analyzed consists of those participants with a baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 12; Sitagliptin, n=6217, Placebo, n=6092 | -0.2 Percentage of HbA1c | Standard Deviation 1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 36; Sitagliptin, n=3227, Placebo, n=3083 | -0.1 Percentage of HbA1c | Standard Deviation 1.1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 8; Sitagliptin, n=6294, Placebo, n=6197 | -0.3 Percentage of HbA1c | Standard Deviation 0.9 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 48; Sitagliptin, n=1271, Placebo, n=1224 | 0.0 Percentage of HbA1c | Standard Deviation 1.1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 24; Sitagliptin, n=5668, Placebo, n=5475 | -0.1 Percentage of HbA1c | Standard Deviation 1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 60; Sitagliptin, n=106, Placebo, n=108 | -0.1 Percentage of HbA1c | Standard Deviation 1 |
| Sitagliptin | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 4; Sitagliptin, n=6632, Placebo, n=6588 | -0.3 Percentage of HbA1c | Standard Deviation 0.8 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 60; Sitagliptin, n=106, Placebo, n=108 | 0.0 Percentage of HbA1c | Standard Deviation 0.9 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 4; Sitagliptin, n=6632, Placebo, n=6588 | 0.1 Percentage of HbA1c | Standard Deviation 0.9 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 8; Sitagliptin, n=6294, Placebo, n=6197 | 0.1 Percentage of HbA1c | Standard Deviation 1 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 12; Sitagliptin, n=6217, Placebo, n=6092 | 0.1 Percentage of HbA1c | Standard Deviation 1 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 24; Sitagliptin, n=5668, Placebo, n=5475 | 0.2 Percentage of HbA1c | Standard Deviation 1.1 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 36; Sitagliptin, n=3227, Placebo, n=3083 | 0.1 Percentage of HbA1c | Standard Deviation 1.1 |
| Placebo | Change From Baseline in HbA1c Over Time (Per Protocol Population) | Month 48; Sitagliptin, n=1271, Placebo, n=1224 | 0.1 Percentage of HbA1c | Standard Deviation 1.2 |
Secondary
Change From Baseline in Renal Function Over Time (Intent to Treat Population)
Change in renal function based on eGFR using the MDRD method.
Time frame: Baseline and up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation. Number of participants analyzed consists of those participants with a baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 12; Sitagliptin, n=5082; Placebo, n=5015 | -1.8 mL/min/1.73 m^2 | Standard Deviation 15.8 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 36; Sitagliptin, n=3037; Placebo, n=2942 | -3.8 mL/min/1.73 m^2 | Standard Deviation 18.1 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 8; Sitagliptin, n=3687; Placebo, n=3648 | -2.4 mL/min/1.73 m^2 | Standard Deviation 14.8 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 48; Sitagliptin, n=1237; Placebo, n=1210 | -4.0 mL/min/1.73 m^2 | Standard Deviation 18.4 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 24; Sitagliptin, n=5157; Placebo, n=5071 | -3.2 mL/min/1.73 m^2 | Standard Deviation 17.9 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 60; Sitagliptin, n=93; Placebo, n=106 | -4.2 mL/min/1.73 m^2 | Standard Deviation 17.4 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 4; Sitagliptin, n=3949; Placebo, n=3977 | -1.8 mL/min/1.73 m^2 | Standard Deviation 14.3 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 60; Sitagliptin, n=93; Placebo, n=106 | -5.7 mL/min/1.73 m^2 | Standard Deviation 17.2 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 4; Sitagliptin, n=3949; Placebo, n=3977 | -0.8 mL/min/1.73 m^2 | Standard Deviation 14.3 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 8; Sitagliptin, n=3687; Placebo, n=3648 | -0.9 mL/min/1.73 m^2 | Standard Deviation 15.2 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 12; Sitagliptin, n=5082; Placebo, n=5015 | -0.5 mL/min/1.73 m^2 | Standard Deviation 16.3 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 24; Sitagliptin, n=5157; Placebo, n=5071 | -1.7 mL/min/1.73 m^2 | Standard Deviation 17.7 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 36; Sitagliptin, n=3037; Placebo, n=2942 | -1.6 mL/min/1.73 m^2 | Standard Deviation 18.7 |
| Placebo | Change From Baseline in Renal Function Over Time (Intent to Treat Population) | Month 48; Sitagliptin, n=1237; Placebo, n=1210 | -2.8 mL/min/1.73 m^2 | Standard Deviation 18.3 |
Secondary
Change From Baseline in Renal Function Over Time (Per Protocol Population)
Change in renal function based on estimated glomerular filtration rate \[eGFR\] using the Modification of Diet in Renal Disease \[MDRD\] method.
Time frame: Baseline and up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data. Number of participants analyzed consists of those participants with a baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 12; Sitagliptin, n=4912, Placebo, n=4778 | -1.8 mL/min/1.73 m^2 | Standard Deviation 15.8 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 36; Sitagliptin, n=2776, Placebo, n=2614 | -3.7 mL/min/1.73 m^2 | Standard Deviation 18 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 8; Sitagliptin, n= 3562; Placebo, n= 3501 | -2.5 mL/min/1.73 m^2 | Standard Deviation 14.9 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 48; Sitagliptin, n=1096, Placebo, n=1056 | -3.7 mL/min/1.73 m^2 | Standard Deviation 18.3 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 24; Sitagliptin, n=4782, Placebo, n=4637 | -3.1 mL/min/1.73 m^2 | Standard Deviation 17.9 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 60; Sitagliptin, n=79, Placebo, n=88 | -3.5 mL/min/1.73 m^2 | Standard Deviation 18.2 |
| Sitagliptin | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 4; Sitagliptin, n= 3859; Placebo, n= 3864 | -1.9 mL/min/1.73 m^2 | Standard Deviation 14.2 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 60; Sitagliptin, n=79, Placebo, n=88 | -6.4 mL/min/1.73 m^2 | Standard Deviation 17.3 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 4; Sitagliptin, n= 3859; Placebo, n= 3864 | -0.8 mL/min/1.73 m^2 | Standard Deviation 14.3 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 8; Sitagliptin, n= 3562; Placebo, n= 3501 | -0.9 mL/min/1.73 m^2 | Standard Deviation 15.1 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 12; Sitagliptin, n=4912, Placebo, n=4778 | -0.5 mL/min/1.73 m^2 | Standard Deviation 16.2 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 24; Sitagliptin, n=4782, Placebo, n=4637 | -1.7 mL/min/1.73 m^2 | Standard Deviation 17.5 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 36; Sitagliptin, n=2776, Placebo, n=2614 | -1.6 mL/min/1.73 m^2 | Standard Deviation 18.8 |
| Placebo | Change From Baseline in Renal Function Over Time (Per Protocol Population) | Month 48; Sitagliptin, n=1096, Placebo, n=1056 | -2.8 mL/min/1.73 m^2 | Standard Deviation 18.4 |
Secondary
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population)
Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.
Time frame: Baseline and up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation. Number of participants analyzed consists of those participants in the intent to treat population with a baseline value for the outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 12; n=1167, n=1115 | 1.3 g/mol Creatinine | Standard Deviation 30.2 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 36; n=537, n=553 | 2.6 g/mol Creatinine | Standard Deviation 25.8 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 8; n=658, n=624 | 2.1 g/mol Creatinine | Standard Deviation 39.4 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 48; n=265, n=256 | 1.9 g/mol Creatinine | Standard Deviation 16.3 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 24; n=1011, n=964 | 0.5 g/mol Creatinine | Standard Deviation 33.1 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 60; n=14, n=18 | -2.5 g/mol Creatinine | Standard Deviation 9.7 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 4; n=677, n=713 | -2.1 g/mol Creatinine | Standard Deviation 27.5 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 60; n=14, n=18 | 6.4 g/mol Creatinine | Standard Deviation 16.4 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 4; n=677, n=713 | -1.4 g/mol Creatinine | Standard Deviation 24.1 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 8; n=658, n=624 | 0.5 g/mol Creatinine | Standard Deviation 44.5 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 12; n=1167, n=1115 | 1.2 g/mol Creatinine | Standard Deviation 32.3 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 24; n=1011, n=964 | 3.1 g/mol Creatinine | Standard Deviation 30.7 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 36; n=537, n=553 | 3.9 g/mol Creatinine | Standard Deviation 30.3 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) | Month 48; n=265, n=256 | 1.6 g/mol Creatinine | Standard Deviation 24.5 |
Secondary
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population)
Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.
Time frame: Baseline and up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data. Number of participants analyzed consists of those participants with a baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 24; Sitagliptin, n=930; Placebo, n=892 | 0.7 g/mol Creatinine | Standard Deviation 34 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 4; Sitagliptin, n=664; Placebo, n=688 | -2.2 g/mol Creatinine | Standard Deviation 27.7 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 36; Sitagliptin, n=488; Placebo, n=513 | 2.5 g/mol Creatinine | Standard Deviation 24 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 12; Sitagliptin, n=1126; Placebo, n=1059 | 0.8 g/mol Creatinine | Standard Deviation 27.7 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 48; Sitagliptin, n=238; Placebo, n=233 | 1.3 g/mol Creatinine | Standard Deviation 15.2 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 60; Sitagliptin, n=13; Placebo, n=17 | -2.7 g/mol Creatinine | Standard Deviation 10.1 |
| Sitagliptin | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 8; Sitagliptin, n=635; Placebo, n=597 | 1.7 g/mol Creatinine | Standard Deviation 38.5 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 60; Sitagliptin, n=13; Placebo, n=17 | 4.8 g/mol Creatinine | Standard Deviation 15.4 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 4; Sitagliptin, n=664; Placebo, n=688 | -1.4 g/mol Creatinine | Standard Deviation 24.6 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 8; Sitagliptin, n=635; Placebo, n=597 | 0.2 g/mol Creatinine | Standard Deviation 45.3 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 12; Sitagliptin, n=1126; Placebo, n=1059 | 1.2 g/mol Creatinine | Standard Deviation 33.1 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 24; Sitagliptin, n=930; Placebo, n=892 | 3.2 g/mol Creatinine | Standard Deviation 31.6 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 36; Sitagliptin, n=488; Placebo, n=513 | 4.0 g/mol Creatinine | Standard Deviation 31 |
| Placebo | Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) | Month 48; Sitagliptin, n=238; Placebo, n=233 | 1.5 g/mol Creatinine | Standard Deviation 25.5 |
Secondary
Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)
Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.
Time frame: Up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population) | 9.7 Percentage of participants |
| Placebo | Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population) | 13.2 Percentage of participants |
p-value: <0.00195% CI: [0.63, 0.79]Cox proportional hazards model
Secondary
Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)
Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.
Time frame: Up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population) | 8.6 Percentage of participants |
| Placebo | Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population) | 11.9 Percentage of participants |
p-value: <0.00195% CI: [0.61, 0.77]Cox proportional hazards model
Secondary
Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)
CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.
Time frame: Up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population) | 10.2 Percentage of participants |
| Placebo | Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population) | 10.2 Percentage of participants |
p-value: <0.00195% CI: [0.89, 1.1]Cox proportional hazards model
Secondary
Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)
CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.
Time frame: Up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population) | 8.4 Percentage of participants |
| Placebo | Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population) | 8.3 Percentage of participants |
p-value: <0.00195% CI: [0.89, 1.11]Cox proportional hazards model
Secondary
Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)
In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)
Time frame: Up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population) | 21.7 Percentage of participants |
| Placebo | Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population) | 27.9 Percentage of participants |
p-value: <0.00195% CI: [0.68, 0.77]Cox proportional hazards model
Secondary
Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)
In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent \[AHA\] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)
Time frame: Up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population) | 18.9 Percentage of participants |
| Placebo | Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population) | 24.5 Percentage of participants |
p-value: <0.00195% CI: [0.65, 0.75]Cox proportional hazards model
Secondary
Percent Incidence of All-cause Mortality (Intent to Treat Population)
Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.
Time frame: Up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent Incidence of All-cause Mortality (Intent to Treat Population) | 7.5 Percentage of participants |
| Placebo | Percent Incidence of All-cause Mortality (Intent to Treat Population) | 7.3 Percentage of participants |
Comparison: Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in mortality due to all causes was assessed by the hazard ratio between the Sitagliptin and Placebo groups.p-value: 0.87595% CI: [0.9, 1.14]Cox proportional hazards model
Secondary
Percent Incidence of All-cause Mortality (Per Protocol Population)
Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.
Time frame: Up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent Incidence of All-cause Mortality (Per Protocol Population) | 4.7 Percentage of participants |
| Placebo | Percent Incidence of All-cause Mortality (Per Protocol Population) | 4.3 Percentage of participants |
Comparison: Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in mortality due to all causes was assessed by the hazard ratio between the Sitagliptin and Placebo groups.p-value: 0.43595% CI: [0.91, 1.24]Cox proportional hazards model
Secondary
Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)
Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.
Time frame: Up to 5 years
Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population) | 3.1 Percentage of participants |
| Placebo | Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population) | 3.1 Percentage of participants |
Comparison: Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in CHF cases requiring hospitalization was assessed by the hazard ratio between the Sitagliptin and Placebo groups.p-value: 0.98395% CI: [0.83, 1.2]Cox proportional hazards model
Secondary
Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)
Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.
Time frame: Up to 5 years
Population: Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population) | 2.8 Percentage of participants |
| Placebo | Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population) | 2.8 Percentage of participants |
Comparison: Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in CHF cases requiring hospitalization was assessed by the hazard ratio between the Sitagliptin and Placebo groups.p-value: 0.85895% CI: [0.81, 1.19]Cox proportional hazards model