Type 2 Diabetes Mellitus
Conditions
Brief summary
This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary study hypothesis is that at Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for ertugliflozin is greater than that for placebo.
Detailed description
The trial includes a 13-15 week run-in period prior to randomization, and a 26-week, double-blind, placebo-controlled treatment period followed by a 78-week double-blind, extension period.
Interventions
Ertugliflozin 5 mg orally (1 ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
Ertugliflozin 15 mg orally (1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
Placebo to ertuglioflozin (1 placebo ertugliflozin 5 mg tablet and/or 1 placebo ertugliflozin 10 mg tablet), orally once daily from Day 1 to Week 104.
OTHERGlimepiride
Open-label Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period.
Placebo to glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of placebo to glimepiride is at the discretion of the investigator.
BIOLOGICALBasal Insulin
Basal insulin will be administered in the initial 26-week period for participants with glucose values exceeding protocol-specified values and for participants requiring rescue therapy in the 78-week extension period. Dosing and titration of basal insulin is at the discretion of the Investigator.
DRUGMetformin
Metformin \>=1500 mg/day, orally, once a day
Sponsors
Pfizer
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of T2DM in accordance to American Diabetes Association guidelines * Participants must be receiving metformin monotherapy for less than 8 weeks prior to study participation or require change in their diabetes regimen to remain eligible to participate in the trial (including discontinuing anti-hyperglycemic agent \[AHA\] therapy) and must have a hemoglobin A1c of 7.0 to 10.5% (53-91 mmol/mol) after at least 8 weeks on a regimen of metformin monotherapy
Exclusion criteria
* History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation * A clinically significant electrocardiogram abnormality * A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer * A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor or glimepiride * On a blood pressure or lipid altering medication that have not been on a stable dose for at least 4 weeks prior to study participation * A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial * Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial * Pregnant or breast-feeding, or is expecting to conceive during the trial, including 14 days following the last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) | Baseline and Week 26 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) | Up to Week 106 | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment. |
| Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) | Up to Week 104 | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) | Baseline and Week 26 | This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) | Baseline and Week 26 | This change from baseline reflects the Week 26 sitting diastolic blood pressure (DBP) minus the Week 0 sitting DBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | Week 26 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 | Up to Week 26 | Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. |
| Time to Glycemic Rescue Therapy at Week 26 | Week 26 | Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. |
| Change From Baseline in A1C at Week 52 (Excluding Rescue Approach) | Baseline and Week 52 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 52 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) | Baseline and Week 52 | Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach) | Week 52 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach) | Week 52 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 | Up to Week 52 | Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. |
| Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach) | Baseline and Week 52 | The change in body weight from baseline reflects the Week 52 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) | Baseline and Week 52 | This change from baseline reflects the Week 52 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) | Baseline and Week 52 | This change from baseline reflects the Week 52 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in A1C at Week 104 (Excluding Rescue Approach) | Baseline and Week 104 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 104 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) | Baseline and Week 104 | Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 104 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 104 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach) | Week 104 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach) | Week 104 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 | Up to Week 104 | Per protocol participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. |
| Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach) | Baseline and Week 104 | The change in body weight from baseline reflects the Week 104 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) | Baseline and Week 104 | This change from baseline reflects the Week 104 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) | Baseline and Week 104 | This change from baseline reflects the Week 104 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30 | Pharmacokinetic samples were collected at approximately 24 hours following the prior day's dose and before administration of the current day's dose. The lower limit of quantitation (LLOQ) was 0.500 mg/mL. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 26 | BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 26 | BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 26 | BMD at the total hip was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 26 | BMD at the distal forearm was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach) | Baseline and Week 26 | CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) | Baseline and Week 26 | P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) | Baseline and Week 26 | PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 52 | BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 52 | BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 52 | BMD at the total hip was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 52 | BMD at the distal forearm was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) | Baseline and Week 52 | CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) | Baseline and Week 52 | P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) | Baseline and Week 52 | PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 104 | BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 104 | BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 104 | BMD at the total hip was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) | Baseline and Week 26 | Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at Week 0) which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) | Baseline and Week 104 | CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) | Baseline and Week 104 | P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) | Baseline and Week 104 | PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | Baseline and Week 104 | BMD at the distal forearm was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. |
| Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) | Baseline and Week 26 | The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
| Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | Week 26 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Glimepiride Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | 209 |
| Ertugliflozin 5 mg Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | 207 |
| Ertugliflozin 15 mg Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | 205 |
| Total | 621 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 3 |
| Overall Study | Death | 3 | 1 | 2 |
| Overall Study | Excluded Medication | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 5 | 6 |
| Overall Study | Non-Compliance With Study Drug | 1 | 0 | 0 |
| Overall Study | Participant moved | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 18 | 10 | 13 |
Baseline characteristics
| Characteristic | Placebo/Glimepiride | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 8.7 | 56.6 Years STANDARD_DEVIATION 8.2 | 56.9 Years STANDARD_DEVIATION 9.4 | 56.6 Years STANDARD_DEVIATION 8.8 |
| Baseline Hemoglobin A1C (A1C) | 8.17 Percentage A1C STANDARD_DEVIATION 0.9 | 8.06 Percentage A1C STANDARD_DEVIATION 0.89 | 8.13 Percentage A1C STANDARD_DEVIATION 0.93 | 8.12 Percentage A1C STANDARD_DEVIATION 0.9 |
| BMD as Measured by DXA at the Distal Forearm | 0.81 g/cm^2 STANDARD_DEVIATION 0.14 | 0.81 g/cm^2 STANDARD_DEVIATION 0.14 | 0.79 g/cm^2 STANDARD_DEVIATION 0.13 | 0.80 g/cm^2 STANDARD_DEVIATION 0.14 |
| BMD as Measured by DXA of the Lumbar Spine (L1-L4) | 1.15 g/cm^2 STANDARD_DEVIATION 0.18 | 1.13 g/cm^2 STANDARD_DEVIATION 0.18 | 1.10 g/cm^2 STANDARD_DEVIATION 0.17 | 1.13 g/cm^2 STANDARD_DEVIATION 0.18 |
| BMD as Measured by DXA of the Total hip | 1.06 g/cm^2 STANDARD_DEVIATION 0.15 | 1.07 g/cm^2 STANDARD_DEVIATION 0.15 | 1.04 g/cm^2 STANDARD_DEVIATION 0.14 | 1.06 g/cm^2 STANDARD_DEVIATION 0.15 |
| Body Weight | 84.5 Kilograms STANDARD_DEVIATION 17.1 | 84.8 Kilograms STANDARD_DEVIATION 17.2 | 85.3 Kilograms STANDARD_DEVIATION 16.5 | 84.9 Kilograms STANDARD_DEVIATION 16.9 |
| Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) | 268.3 ng/L STANDARD_DEVIATION 132.9 | 266.9 ng/L STANDARD_DEVIATION 129.9 | 273.0 ng/L STANDARD_DEVIATION 135.2 | 269.4 ng/L STANDARD_DEVIATION 132.5 |
| Bone Biomarker Parathyroid Hormone (PTH) | 19.29 ng/L STANDARD_DEVIATION 8.17 | 19.52 ng/L STANDARD_DEVIATION 6.91 | 19.97 ng/L STANDARD_DEVIATION 7.73 | 19.59 ng/L STANDARD_DEVIATION 7.62 |
| Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) | 32.0 microgm/L STANDARD_DEVIATION 15 | 32.8 microgm/L STANDARD_DEVIATION 14.5 | 31.6 microgm/L STANDARD_DEVIATION 16.5 | 32.1 microgm/L STANDARD_DEVIATION 15.3 |
| Bone Mineral Density (BMD) as Measured by Dual Energy X-Ray Absorptiometry (DXA) of the Femoral Neck | 0.92 g/cm^2 STANDARD_DEVIATION 0.17 | 0.92 g/cm^2 STANDARD_DEVIATION 0.16 | 0.89 g/cm^2 STANDARD_DEVIATION 0.15 | 0.91 g/cm^2 STANDARD_DEVIATION 0.16 |
| Diastolic Blood Pressure (DBP) | 77.45 mmHg STANDARD_DEVIATION 7.55 | 78.45 mmHg STANDARD_DEVIATION 8.32 | 78.08 mmHg STANDARD_DEVIATION 7.45 | 77.99 mmHg STANDARD_DEVIATION 7.78 |
| Estimated Glomerular Filtration Rate (eGFR) | 91.6 mL/min/1.73 m^2 STANDARD_DEVIATION 19.8 | 88.9 mL/min/1.73 m^2 STANDARD_DEVIATION 17.5 | 91.1 mL/min/1.73 m^2 STANDARD_DEVIATION 20.6 | 90.5 mL/min/1.73 m^2 STANDARD_DEVIATION 19.3 |
| Fasting Plasma Glucose (FPG) | 169.1 mg/dL STANDARD_DEVIATION 41.7 | 168.1 mg/dL STANDARD_DEVIATION 45.5 | 167.5 mg/dL STANDARD_DEVIATION 44.4 | 168.3 mg/dL STANDARD_DEVIATION 43.8 |
| Menopausal Status Male | 98 Participants | 97 Participants | 93 Participants | 288 Participants |
| Menopausal Status Perimenopausal or <3 yrs. postmen. | 9 Participants | 10 Participants | 11 Participants | 30 Participants |
| Menopausal Status Premenopausal Women | 16 Participants | 17 Participants | 16 Participants | 49 Participants |
| Menopausal Status Women ≥3 years postmenopausal | 86 Participants | 83 Participants | 85 Participants | 254 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 34 Participants | 35 Participants | 100 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 22 Participants | 23 Participants | 64 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 17 Participants | 14 Participants | 46 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 144 Participants | 134 Participants | 133 Participants | 411 Participants |
| Sex: Female, Male Female | 111 Participants | 110 Participants | 112 Participants | 333 Participants |
| Sex: Female, Male Male | 98 Participants | 97 Participants | 93 Participants | 288 Participants |
| Sitting Systolic Blood Pressure (SBP) | 129.30 mmHg STANDARD_DEVIATION 15.43 | 130.48 mmHg STANDARD_DEVIATION 13.77 | 130.37 mmHg STANDARD_DEVIATION 12 | 130.05 mmHg STANDARD_DEVIATION 13.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 209 | 1 / 207 | 2 / 205 |
| other Total, other adverse events | 103 / 209 | 79 / 207 | 100 / 205 |
| serious Total, serious adverse events | 22 / 209 | 20 / 207 | 20 / 205 |
Outcome results
Primary
Change From Baseline in A1C at Week 26 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) | -0.03 Percent A1C |
| Ertugliflozin 5 mg | Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) | -0.73 Percent A1C |
| Ertugliflozin 15 mg | Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) | -0.91 Percent A1C |
p-value: <0.00195% CI: [-1.05, -0.71]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-0.87, -0.53]Constrained Longitudinal Data Analysis
Primary
Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment.
Time frame: Up to Week 104
Population: All participants who received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) | 2.4 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) | 3.4 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) | 3.9 Percentage of Participants |
95% CI: [-2.1, 5.4]
95% CI: [-2.5, 4.7]
Primary
Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment.
Time frame: Up to Week 106
Population: All participants who received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) | 77.5 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) | 70.5 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) | 75.6 Percentage of Participants |
Secondary
Change From Baseline in A1C at Week 104 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 104 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in A1C at Week 104 (Excluding Rescue Approach) | -0.58 Percent A1C | Standard Deviation 0.93 |
| Ertugliflozin 5 mg | Change From Baseline in A1C at Week 104 (Excluding Rescue Approach) | -0.60 Percent A1C | Standard Deviation 0.97 |
| Ertugliflozin 15 mg | Change From Baseline in A1C at Week 104 (Excluding Rescue Approach) | -0.89 Percent A1C | Standard Deviation 0.9 |
Secondary
Change From Baseline in A1C at Week 52 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 52 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in A1C at Week 52 (Excluding Rescue Approach) | -0.68 Percent A1C | Standard Deviation 0.99 |
| Ertugliflozin 5 mg | Change From Baseline in A1C at Week 52 (Excluding Rescue Approach) | -0.72 Percent A1C | Standard Deviation 0.95 |
| Ertugliflozin 15 mg | Change From Baseline in A1C at Week 52 (Excluding Rescue Approach) | -0.96 Percent A1C | Standard Deviation 0.88 |
Secondary
Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach)
The change in body weight from baseline reflects the Week 104 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach) | -0.18 Kilograms | Standard Deviation 3.38 |
| Ertugliflozin 5 mg | Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach) | -3.77 Kilograms | Standard Deviation 4.29 |
| Ertugliflozin 15 mg | Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach) | -3.63 Kilograms | Standard Deviation 3.86 |
Secondary
Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach)
The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) | -1.33 Kilograms |
| Ertugliflozin 5 mg | Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) | -3.01 Kilograms |
| Ertugliflozin 15 mg | Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) | -2.93 Kilograms |
p-value: <0.00195% CI: [-2.16, -1.03]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-2.24, -1.11]Constrained Longitudinal Data Analysis
Secondary
Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach)
The change in body weight from baseline reflects the Week 52 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach) | 0.07 Kilograms | Standard Deviation 2.85 |
| Ertugliflozin 5 mg | Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach) | -3.23 Kilograms | Standard Deviation 3.68 |
| Ertugliflozin 15 mg | Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach) | -3.35 Kilograms | Standard Deviation 3.27 |
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach)
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 104 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 104 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) | -10.9 mg/dL | Standard Deviation 44.3 |
| Ertugliflozin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) | -18.2 mg/dL | Standard Deviation 43.5 |
| Ertugliflozin 15 mg | Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) | -28.2 mg/dL | Standard Deviation 44.9 |
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach)
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at Week 0) which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) | -0.85 mg/dL |
| Ertugliflozin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) | -27.54 mg/dL |
| Ertugliflozin 15 mg | Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) | -39.10 mg/dL |
p-value: <0.00195% CI: [-44.5, -31.99]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-32.9, -20.48]Constrained Longitudinal Data Analysis
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy)
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) | -12.0 mg/dL | Standard Deviation 40 |
| Ertugliflozin 5 mg | Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) | -22.4 mg/dL | Standard Deviation 39.3 |
| Ertugliflozin 15 mg | Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) | -35.2 mg/dL | Standard Deviation 40.7 |
Secondary
Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach)
This change from baseline reflects the Week 104 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) | -0.46 mmHg | Standard Deviation 8.77 |
| Ertugliflozin 5 mg | Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) | -2.36 mmHg | Standard Deviation 9.23 |
| Ertugliflozin 15 mg | Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) | -1.52 mmHg | Standard Deviation 8.61 |
Secondary
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach)
This change from baseline reflects the Week 26 sitting diastolic blood pressure (DBP) minus the Week 0 sitting DBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) | 0.23 mmHg |
| Ertugliflozin 5 mg | Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) | -1.59 mmHg |
| Ertugliflozin 15 mg | Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) | -2.19 mmHg |
p-value: 0.00195% CI: [-3.86, -0.98]Constrained Longitudinal Data Analysis
p-value: 0.01395% CI: [-3.24, -0.39]Constrained Longitudinal Data Analysis
Secondary
Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach)
This change from baseline reflects the Week 52 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) | 0.38 mmHg | Standard Deviation 8.16 |
| Ertugliflozin 5 mg | Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) | -1.40 mmHg | Standard Deviation 9.6 |
| Ertugliflozin 15 mg | Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) | -1.19 mmHg | Standard Deviation 7.74 |
Secondary
Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach)
This change from baseline reflects the Week 104 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) | 0.05 mmHg | Standard Deviation 13.76 |
| Ertugliflozin 5 mg | Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) | -3.61 mmHg | Standard Deviation 12.78 |
| Ertugliflozin 15 mg | Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) | -3.13 mmHg | Standard Deviation 14.11 |
Secondary
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach)
This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) | -0.70 mmHg |
| Ertugliflozin 5 mg | Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) | -4.38 mmHg |
| Ertugliflozin 15 mg | Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) | -5.20 mmHg |
p-value: <0.00195% CI: [-6.81, -2.19]Constrained Longitudinal Data Analysis
p-value: 0.00295% CI: [-5.96, -1.39]Constrained Longitudinal Data Analysis
Secondary
Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach)
This change from baseline reflects the Week 52 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) | 0.65 mmHg | Standard Deviation 13.38 |
| Ertugliflozin 5 mg | Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) | -2.63 mmHg | Standard Deviation 14.4 |
| Ertugliflozin 15 mg | Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) | -4.28 mmHg | Standard Deviation 13.28 |
Secondary
Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach)
Pharmacokinetic samples were collected at approximately 24 hours following the prior day's dose and before administration of the current day's dose. The lower limit of quantitation (LLOQ) was 0.500 mg/mL. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30
Population: All subjects as treated (including those with all concentrations below the lower limit of quantification) were included in the calculation of the summary statistics. Numbers of participants with non-missing concentrations at the respective time points are displayed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Glimepiride | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 30:Pre-dose | 0.15 ng/mL | Standard Deviation 1.07 |
| Placebo/Glimepiride | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 12:60 mins post-dose | NA ng/mL | — |
| Placebo/Glimepiride | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 18:60 mins post-dose | 0.01 ng/mL | Standard Deviation 0.09 |
| Placebo/Glimepiride | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 6:Pre-dose | NA ng/mL | — |
| Placebo/Glimepiride | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 18:Pre-dose | 0.01 ng/mL | Standard Deviation 0.1 |
| Placebo/Glimepiride | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 12:Pre-dose | NA ng/mL | — |
| Ertugliflozin 5 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 30:Pre-dose | 12.66 ng/mL | Standard Deviation 25.5 |
| Ertugliflozin 5 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 12:Pre-dose | 12.34 ng/mL | Standard Deviation 26.07 |
| Ertugliflozin 5 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 12:60 mins post-dose | 74.84 ng/mL | Standard Deviation 51.58 |
| Ertugliflozin 5 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 18:Pre-dose | 9.91 ng/mL | Standard Deviation 21.18 |
| Ertugliflozin 5 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 18:60 mins post-dose | 74.39 ng/mL | Standard Deviation 49.77 |
| Ertugliflozin 5 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 6:Pre-dose | 14.89 ng/mL | Standard Deviation 28.11 |
| Ertugliflozin 15 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 18:60 mins post-dose | 214.96 ng/mL | Standard Deviation 147.36 |
| Ertugliflozin 15 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 30:Pre-dose | 30.55 ng/mL | Standard Deviation 60.33 |
| Ertugliflozin 15 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 12:Pre-dose | 29.23 ng/mL | Standard Deviation 55.63 |
| Ertugliflozin 15 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 18:Pre-dose | 24.46 ng/mL | Standard Deviation 39.97 |
| Ertugliflozin 15 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 12:60 mins post-dose | 228.13 ng/mL | Standard Deviation 139.14 |
| Ertugliflozin 15 mg | Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | Week 6:Pre-dose | 38.38 ng/mL | Standard Deviation 74.83 |
Secondary
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104
Per protocol participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
Time frame: Up to Week 104
Population: All participants who received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 | 24.4 Percentage of participants |
| Ertugliflozin 5 mg | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 | 11.1 Percentage of participants |
| Ertugliflozin 15 mg | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 | 10.7 Percentage of participants |
Secondary
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26
Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
Time frame: Up to Week 26
Population: All participants who received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 | 17.7 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 | 2.9 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 | 1.5 Percentage of Participants |
p-value: <0.00195% CI: [-22.2, -11.2]Miettinen & Nurminen method
p-value: <0.00195% CI: [-20.9, -9.4]Miettinen & Nurminen method.
Secondary
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52
Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
Time frame: Up to Week 52
Population: All participants who received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 | 17.2 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 | 4.3 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 | 1.5 Percentage of Participants |
Secondary
Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Week 104
Population: All randomized participants who received at least one dose of investigational product. Any participant without post-baseline data at Week 104 was assumed to be not at goal, where goal was A1C \<6.5% for the calculation of the percentages.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach) | 7.2 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach) | 10.6 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach) | 12.2 Percentage of Participants |
Secondary
Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | 2.9 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | 8.7 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | 12.2 Percentage of Participants |
p-value: <0.00195% CI: [2.1, 13.9]Regression, Logistic
p-value: 0.02395% CI: [1.17, 8.22]Regression, Logistic
Secondary
Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Week 52
Population: All randomized participants who received at least one dose of investigational product. Any participant without post-baseline data at Week 52 was assumed to be not at goal, where goal was A1C \<6.5%, for the calculation of the percentages.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach) | 11.0 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach) | 10.6 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach) | 14.6 Percentage of Participants |
Secondary
Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Week 104
Population: All randomized participants who received at least one dose of investigational product. Any participant without post-baseline data at Week 104 was assumed to be not at goal, where goal was A1C \<7%, for the calculation of the percentages.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach) | 19.1 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach) | 24.6 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach) | 33.7 Percentage of Participants |
Secondary
Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Week 26
Population: All randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at baseline or post-baseline up to Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | 15.8 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | 35.3 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) | 40.0 Percentage of Participants |
p-value: <0.00195% CI: [2.64, 7.62]Regression, Logistic
p-value: <0.00195% CI: [1.81, 5.06]Regression, Logistic
Secondary
Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
Time frame: Week 52
Population: All randomized participants who received at least one dose of investigational product. Any participant without post-baseline data at Week 52 was assumed to be not at goal, where goal was A1C \<7%, for the calculation of the percentages.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Glimepiride | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach) | 30.6 Percentage of Participants |
| Ertugliflozin 5 mg | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach) | 34.8 Percentage of Participants |
| Ertugliflozin 15 mg | Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach) | 36.6 Percentage of Participants |
Secondary
Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach)
BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -1.23 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -1.11 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -0.96 Percent change |
95% CI: [-0.58, 1.13]
95% CI: [-0.7, 0.93]
Secondary
Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach)
BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | 0.09 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | -0.19 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | -0.13 Percent change |
95% CI: [-1.01, 0.56]
97% CI: [-1.06, 0.5]
Secondary
Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach)
BMD at the total hip was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -1.18 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -1.72 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -2.02 Percent change |
95% CI: [-1.44, -0.24]
95% CI: [-1.12, 0.05]
Secondary
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach)
BMD at the distal forearm was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | 0.06 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.15 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.13 Percent change |
95% CI: [-0.76, 0.39]
95% CI: [-0.78, 0.35]
Secondary
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach)
BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -0.40 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -0.10 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | 0.30 Percent change |
95% CI: [0, 1.39]
95% CI: [-0.38, 0.99]
Secondary
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach)
BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | 0.22 Percentage change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | -0.01 Percentage change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | 0.12 Percentage change |
95% CI: [-0.71, 0.5]
97% CI: [-0.83, 0.37]
Secondary
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach)
BMD at the total hip was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -0.63 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -0.55 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -0.36 Percent change |
95% CI: [-0.15, 0.68]
95% CI: [-0.33, 0.48]
Secondary
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach)
BMD at the distal forearm was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.44 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.59 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.39 Percent change |
95% CI: [-0.61, 0.72]
95% CI: [-0.78, 0.49]
Secondary
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach)
BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -0.69 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -0.49 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | -0.44 Percent change |
95% CI: [-0.48, 0.98]
95% CI: [-0.51, 0.91]
Secondary
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach)
BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | -0.10 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | -0.28 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | 0.07 Percent change |
95% CI: [-0.53, 0.88]
97% CI: [-0.88, 0.51]
Secondary
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach)
BMD at the total hip was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -0.82 Percent change |
| Ertugliflozin 5 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -1.04 Percent change |
| Ertugliflozin 15 mg | Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | -1.32 Percent change |
95% CI: [-0.95, -0.04]
95% CI: [-0.66, 0.23]
Secondary
Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach)
CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 26.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach) | 10.8 Percent change | Standard Deviation 106.6 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach) | 51.9 Percent change | Standard Deviation 121.9 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach) | 80.2 Percent change | Standard Deviation 149.7 |
Secondary
Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach)
CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) | 19.29 Percent change | Standard Deviation 71.73 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) | 26.94 Percent change | Standard Deviation 58.44 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) | 32.53 Percent change | Standard Deviation 59.29 |
Secondary
Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach)
CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) | 15.54 Percent change | Standard Deviation 43.34 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) | 34.36 Percent change | Standard Deviation 52.74 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) | 41.57 Percent change | Standard Deviation 50.69 |
Secondary
Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach)
P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) | 19.38 Percent change | Standard Deviation 93.02 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) | 10.11 Percent change | Standard Deviation 39.14 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) | 24.21 Percent change | Standard Deviation 83.23 |
Secondary
Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach)
P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) | 24.50 Percent Change | Standard Deviation 120.29 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) | 8.41 Percent Change | Standard Deviation 30.95 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) | 19.79 Percent Change | Standard Deviation 79.57 |
Secondary
Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach)
PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 26.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) | -0.98 Percent change | Standard Deviation 6.71 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) | 0.28 Percent change | Standard Deviation 7.52 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) | 0.14 Percent change | Standard Deviation 7.53 |
Secondary
Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach)
P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 26
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 26.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) | 0.5 Percent change | Standard Deviation 11.7 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) | 0.8 Percent change | Standard Deviation 12.1 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) | 0.5 Percent change | Standard Deviation 15 |
Secondary
Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach)
PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 104.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) | 10.12 Percent change | Standard Deviation 60.13 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) | 8.16 Percent change | Standard Deviation 40.97 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) | 5.46 Percent change | Standard Deviation 38.53 |
Secondary
Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach)
PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 52
Population: All randomized participants who have received at least one dose of investigational product and have measurements of the respective endpoint at both baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Glimepiride | Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) | 8.11 Percent Change | Standard Deviation 52.05 |
| Ertugliflozin 5 mg | Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) | 11.09 Percent Change | Standard Deviation 41.8 |
| Ertugliflozin 15 mg | Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) | 2.48 Percent Change | Standard Deviation 36.57 |
Secondary
Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach)
BMD at the distal forearm was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Time frame: Baseline and Week 104
Population: All randomized participants who have received at least one dose of investigational product and have a measurement at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo/Glimepiride | Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.58 Percent change |
| Ertugliflozin 5 mg | Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.40 Percent change |
| Ertugliflozin 15 mg | Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | -0.64 Percent change |
95% CI: [-0.77, 0.65]
95% CI: [-0.5, 0.85]
Secondary
Time to Glycemic Rescue Therapy at Week 26
Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
Time frame: Week 26
Population: All participants who received at least one dose of investigational product and received glycemic rescue through Week 26.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Glimepiride | Time to Glycemic Rescue Therapy at Week 26 | 105 Days |
| Ertugliflozin 5 mg | Time to Glycemic Rescue Therapy at Week 26 | 112 Days |
| Ertugliflozin 15 mg | Time to Glycemic Rescue Therapy at Week 26 | 139 Days |