Phase 3
Completed N=621
A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).
Source: ClinicalTrials.gov NCT02033889 ↗Enrolled (actual)
621
Serious AEs
10.0%
Results posted
Sep 2018
Primary outcomePrimary: Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) — -0.03; -0.73; -0.91 Percent A1C — p=<0.001
◆ Published Evidence
Highly cited
189citations · ~24 / year
Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET).
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.
Linked Publications (5)
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Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET).
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Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials.
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Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials.
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Efficacy and Safety of Ertugliflozin Added to Metformin: A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity.
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Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) |
-0.03; -0.73; -0.91 | <0.001 sig |
| PRIMARY Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) |
77.5; 70.5; 75.6 | — |
| PRIMARY Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) |
2.4; 3.4; 3.9 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) |
-0.85; -27.54; -39.10 | <0.001 sig |
| SECONDARY Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) |
-1.33; -3.01; -2.93 | <0.001 sig |
| SECONDARY Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) |
15.8; 35.3; 40.0 | <0.001 sig |
| SECONDARY Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) |
-0.70; -4.38; -5.20 | <0.001 sig |
| SECONDARY Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) |
0.23; -1.59; -2.19 | 0.001 sig |
| SECONDARY 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; 8.7; 12.2 | <0.001 sig |
| SECONDARY Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 |
17.7; 2.9; 1.5 | <0.001 sig |
| SECONDARY Time to Glycemic Rescue Therapy at Week 26 |
105; 112; 139 | — |
| SECONDARY Change From Baseline in A1C at Week 52 (Excluding Rescue Approach) |
-0.68; -0.72; -0.96 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) |
-12.0; -22.4; -35.2 | — |
| SECONDARY Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach) |
30.6; 34.8; 36.6 | — |
| SECONDARY Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach) |
11.0; 10.6; 14.6 | — |
| SECONDARY Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 |
17.2; 4.3; 1.5 | — |
| SECONDARY Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach) |
0.07; -3.23; -3.35 | — |
| SECONDARY Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) |
0.65; -2.63; -4.28 | — |
| SECONDARY Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) |
0.38; -1.40; -1.19 | — |
| SECONDARY Change From Baseline in A1C at Week 104 (Excluding Rescue Approach) |
-0.58; -0.60; -0.89 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) |
-10.9; -18.2; -28.2 | — |
| SECONDARY Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach) |
19.1; 24.6; 33.7 | — |
| SECONDARY Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach) |
7.2; 10.6; 12.2 | — |
| SECONDARY Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 |
24.4; 11.1; 10.7 | — |
| SECONDARY Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach) |
-0.18; -3.77; -3.63 | — |
| SECONDARY Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) |
0.05; -3.61; -3.13 | — |
| SECONDARY Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) |
-0.46; -2.36; -1.52 | — |
| SECONDARY Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) |
NA; 14.89; 38.38; NA; 12.34; 29.23 | — |
| 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) |
0.22; -0.01; 0.12 | — |
| 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) |
-0.40; -0.10; 0.30 | — |
| 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) |
-0.63; -0.55; -0.36 | — |
| 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) |
0.06; -0.15; -0.13 | — |
| 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) |
10.8; 51.9; 80.2 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) |
0.5; 0.8; 0.5 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) |
-0.98; 0.28; 0.14 | — |
| 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) |
-0.10; -0.28; 0.07 | — |
| 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) |
-0.69; -0.49; -0.44 | — |
| 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) |
-0.82; -1.04; -1.32 | — |
| 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) |
-0.44; -0.59; -0.39 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) |
15.54; 34.36; 41.57 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) |
24.50; 8.41; 19.79 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) |
8.11; 11.09; 2.48 | — |
| 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) |
0.09; -0.19; -0.13 | — |
| 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) |
-1.23; -1.11; -0.96 | — |
| 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) |
-1.18; -1.72; -2.02 | — |
| SECONDARY Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) |
-0.58; -0.40; -0.64 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) |
19.29; 26.94; 32.53 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) |
19.38; 10.11; 24.21 | — |
| SECONDARY Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) |
10.12; 8.16; 5.46 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02033889) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.