Type 2 Diabetes MellitusPhase 3NCT02033889

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).

A Phase 3 study testing Ertugliflozin 5 mg, Ertugliflozin 15 mg and Glimepiride in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Ertugliflozin 5 mg, Ertugliflozin 15 mg and Glimepiride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 621 participants
Where: No sites listed yet
Study dates: 13 Dec 2013to 3 Aug 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study With a 78-Week Extension To Evaluate The Efficacy And Safety Of Ertugliflozin In Subjects With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy.

Read the 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.

Conditions: Type 2 Diabetes Mellitus
Being tested: Ertugliflozin 5 mg, Ertugliflozin 15 mg, Placebo to Ertugliflozin, Glimepiride, Placebo to Glimepiride
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ertugliflozin 5 mgDrug
Also called MK-8835
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 mgDrug
Also called MK-8835
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 ErtugliflozinDrug
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.
GlimepirideOther
Also called Amaryl, GLIMPID, GLIMY
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 GlimepirideDrug
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.
Basal InsulinBiological
Also called Insulin glargine, Insulin detemir, NPH insulin, Degludec
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.
MetforminDrug
Also called Glucophage XR, Carbophage SR, Riomet, Fortamet
Metformin >=1500 mg/day, orally, once a day

Study groups in NCT02033889
Study group	Role	What they receive
Ertuglifozin 5 mg	Experimental	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. Receives: Drug: Ertugliflozin 5 mg; Drug: Placebo to Ertugliflozin; Other: Glimepiride; Drug: Placebo to Glimepiride; Biological: Basal Insulin; Drug: Metformin
Ertugliflozin 15 mg	Experimental	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. Receives: Drug: Ertugliflozin 15 mg; Other: Glimepiride; Drug: Placebo to Glimepiride; Biological: Basal Insulin; Drug: Metformin
Placebo/Glimepiride	Placebo comparator	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. Receives: Drug: Placebo to Ertugliflozin; Other: Glimepiride; Biological: Basal Insulin; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 26
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.
Measured: Up to Week 106
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.
Measured: Up to Week 104

Secondary outcomes (46)

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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Week 26
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.
Measured: Up to Week 26
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.
Measured: Week 26
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Week 52
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.
Measured: Week 52
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.
Measured: Up to Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Week 104
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.
Measured: Week 104
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.
Measured: Up to Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Dec 20133 Aug 2017

First posted13 Jan 2014 (estimated)
Study start13 Dec 2013
Primary completion3 Aug 2017
Study completion3 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (11)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 621 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02033889
Sponsor's protocol ID: 8835-007
Other IDs: 2013-003290-95, B1521017, MK-8835-007
Status last verified: Aug 2018
First submitted: 9 Jan 2014
Last updated: 10 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Rosenstock J, Frias J, Pall D, Charbonnel B, Pascu R, Saur D, Darekar A, Huyck S, Shi H, Lauring B, Terra SG. 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). Diabetes Obes Metab. 2018 Mar;20(3):520-529. doi: 10.1111/dom.13103. Epub 2017 Oct 2.
PubMed 28857451
Ji L, Liu J, Xu ZJ, Wei Z, Zhang R, Malkani S, Cater NB, Frederich R. Efficacy and Safety of Ertugliflozin Added to Metformin: A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity. Diabetes Ther. 2023 Feb;14(2):319-334. doi: 10.1007/s13300-022-01345-6. Epub 2023 Feb 3.
PubMed 36763328
Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
PubMed 34213819
Gallo S, Calle RA, Terra SG, Pong A, Tarasenko L, Raji A. Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials. Diabetes Ther. 2020 Aug;11(8):1849-1860. doi: 10.1007/s13300-020-00867-1. Epub 2020 Jul 9.
PubMed 32648108
Patel S, Hickman A, Frederich R, Johnson S, Huyck S, Mancuso JP, Gantz I, Terra SG. Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials. Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.
PubMed 32372382
Liu J, Tarasenko L, Pong A, Huyck S, Wu L, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Aug;36(8):1277-1284. doi: 10.1080/03007995.2020.1760228. Epub 2020 May 13.
PubMed 32324082
Liu J, Tarasenko L, Pong A, Huyck S, Patel S, Hickman A, Mancuso JP, Ellison MC, Gantz I, Terra SG. Efficacy and safety of ertugliflozin in Hispanic/Latino patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Jul;36(7):1097-1106. doi: 10.1080/03007995.2020.1760227. Epub 2020 May 13.
PubMed 32324065
Cherney DZI, Heerspink HJL, Frederich R, Maldonado M, Liu J, Pong A, Xu ZJ, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Effects of ertugliflozin on renal function over 104 weeks of treatment: a post hoc analysis of two randomised controlled trials. Diabetologia. 2020 Jun;63(6):1128-1140. doi: 10.1007/s00125-020-05133-4. Epub 2020 Mar 31.
PubMed 32236732
Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020 Apr;22(4):574-582. doi: 10.1111/dom.13931. Epub 2020 Jan 3.
PubMed 31797522
Liu J, Pong A, Gallo S, Darekar A, Terra SG. Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials. Cardiovasc Diabetol. 2019 May 7;18(1):59. doi: 10.1186/s12933-019-0856-7.
PubMed 31064361
Gallo S, Charbonnel B, Goldman A, Shi H, Huyck S, Darekar A, Lauring B, Terra SG. Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial. Diabetes Obes Metab. 2019 Apr;21(4):1027-1036. doi: 10.1111/dom.13631. Epub 2019 Feb 14.
PubMed 30614616

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study With a 78-Week Extension To Evaluate The Efficacy And Safety Of Ertugliflozin In Subjects With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy.
ClinicalTrials.gov ID: NCT02033889
Acronym / sponsor ID: 8835-007
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 621 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Collaborators: Pfizer
Study start: 13 Dec 2013 (actual)
Primary completion: 3 Aug 2017 (actual)
Study completion: 3 Aug 2017 (actual)
First posted: 13 Jan 2014 (estimated)
Results: Posted 10 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Ertuglifozin 5 mg	Experimental	Drug: Ertugliflozin 5 mg, Drug: Placebo to Ertugliflozin, Other: Glimepiride, Drug: Placebo to Glimepiride, Biological: Basal Insulin, Drug: MetforminErtugliflozin 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.
Ertugliflozin 15 mg	Experimental	Drug: Ertugliflozin 15 mg, Other: Glimepiride, Drug: Placebo to Glimepiride, Biological: Basal Insulin, Drug: MetforminErtugliflozin 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.
Placebo/Glimepiride	Placebo comparator	Drug: Placebo to Ertugliflozin, Other: Glimepiride, Biological: Basal Insulin, Drug: MetforminPlacebo 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ertugliflozin 5 mgAlso: MK-8835Ertugliflozin 5 mg orally (1 ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.	Drug	Ertuglifozin 5 mg
Ertugliflozin 15 mgAlso: MK-8835Ertugliflozin 15 mg orally (1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.	Drug	Ertugliflozin 15 mg
Placebo to ErtugliflozinPlacebo 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.	Drug	Ertuglifozin 5 mg, Placebo/Glimepiride
GlimepirideAlso: Amaryl, GLIMPID, GLIMYOpen-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.	Other	Ertugliflozin 15 mg, Ertuglifozin 5 mg, Placebo/Glimepiride
Placebo to GlimepiridePlacebo 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.	Drug	Ertugliflozin 15 mg, Ertuglifozin 5 mg
Basal InsulinAlso: Insulin glargine, Insulin detemir, NPH insulin, DegludecBasal 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.	Biological	Ertugliflozin 15 mg, Ertuglifozin 5 mg, Placebo/Glimepiride
MetforminAlso: Glucophage XR, Carbophage SR, Riomet, FortametMetformin >=1500 mg/day, orally, once a day	Drug	Ertugliflozin 15 mg, Ertuglifozin 5 mg, Placebo/Glimepiride

Primary outcome

Change From Baseline in A1C at Week 26 (Excluding Rescue Approach)
Time frame: 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)
Time frame: 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)
Time frame: 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.

46 secondary outcomes

Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach)
Time frame: Baseline and Week 26
Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach)
Time frame: Baseline and Week 26
Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach)
Time frame: Week 26
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach)
Time frame: Baseline and Week 26
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach)
Time frame: Baseline and Week 26
Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach)
Time frame: Week 26
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26
Time frame: Up to Week 26
Time to Glycemic Rescue Therapy at Week 26
Time frame: Week 26
Change From Baseline in A1C at Week 52 (Excluding Rescue Approach)
Time frame: Baseline and Week 52
Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy)
Time frame: Baseline and Week 52
Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach)
Time frame: Week 52
Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach)
Time frame: Week 52
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52
Time frame: Up to Week 52
Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach)
Time frame: Baseline and Week 52
Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach)
Time frame: Baseline and Week 52
Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach)
Time frame: Baseline and Week 52
Change From Baseline in A1C at Week 104 (Excluding Rescue Approach)
Time frame: Baseline and Week 104
Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach)
Time frame: Baseline and Week 104
Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach)
Time frame: Week 104
Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach)
Time frame: Week 104
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104
Time frame: Up to Week 104
Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach)
Time frame: Baseline and Week 104
Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach)
Time frame: Baseline and Week 104
Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach)
Time frame: Baseline and Week 104
Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach)
Time frame: Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30
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)
Time frame: Baseline and Week 26
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 26
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 26
Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 26
Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 26
Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 26
Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 26
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)
Time frame: Baseline and Week 52
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 52
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 52
Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 52
Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 52
Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 52
Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach)
Time frame: Baseline and Week 52
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)
Time frame: Baseline and Week 104

Results and safety

Results posted to the registry on 10 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo/Glimepiride	209	175
Ertugliflozin 5 mg	207	187
Ertugliflozin 15 mg	205	180

Primary outcome: Change From Baseline in A1C at Week 26 (Excluding Rescue Approach)

Time frame: Baseline and Week 26. Least squares mean (95% Confidence Interval). Unit: Percent A1C

Measure	Placebo/Glimepiride n = 209	Ertugliflozin 5 mg n = 207	Ertugliflozin 15 mg n = 205
Value	-0.03 (-0.15 to 0.10)	-0.73 (-0.85 to -0.61)	-0.91 (-1.03 to -0.78)

Placebo/Glimepiride vs Ertugliflozin 15 mg: Difference in Least Squares Means: -0.88 (95% CI -1.05 to -0.71), p <0.001, Constrained Longitudinal Data Analysis
Placebo/Glimepiride vs Ertugliflozin 5 mg: Difference in Least Squares Means: -0.70 (95% CI -0.87 to -0.53), p <0.001, Constrained Longitudinal Data Analysis

Population analysed: 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.

Primary outcome: Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach)

Time frame: Up to Week 106. Number. Unit: Percentage of Participants

Measure	Placebo/Glimepiride n = 209	Ertugliflozin 5 mg n = 207	Ertugliflozin 15 mg n = 205
Value	77.5	70.5	75.6

Population analysed: All participants who received at least one dose of investigational product.

Primary outcome: Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach)

Time frame: Up to Week 104. Number. Unit: Percentage of Participants

Measure	Placebo/Glimepiride n = 209	Ertugliflozin 5 mg n = 207	Ertugliflozin 15 mg n = 205
Value	2.4	3.4	3.9

Placebo/Glimepiride vs Ertugliflozin 15 mg: Difference in % vs Placebo/Glimepiride: 1.5 (95% CI -2.1 to 5.4)
Placebo/Glimepiride vs Ertugliflozin 5 mg: Difference in % vs Placebo/Glimepiride: 1.0 (95% CI -2.5 to 4.7)

Population analysed: All participants who received at least one dose of investigational product.

46 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 106 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo/Glimepiride	22 of 209 (10.5%)	103 of 209 (49.3%)	3 of 209
Ertugliflozin 5 mg	20 of 207 (9.7%)	79 of 207 (38.2%)	1 of 207
Ertugliflozin 15 mg	20 of 205 (9.8%)	100 of 205 (48.8%)	2 of 205

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28857451Rosenstock J, Frias J, Pall D, Charbonnel B, Pascu R, Saur D, Darekar A, Huyck S, Shi H, Lauring B, Terra SG. 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). Diabetes Obes Metab. 2018 Mar;20(3):520-529. doi: 10.1111/dom.13103. Epub 2017 Oct 2.
Derived from this study: PubMed 36763328Ji L, Liu J, Xu ZJ, Wei Z, Zhang R, Malkani S, Cater NB, Frederich R. Efficacy and Safety of Ertugliflozin Added to Metformin: A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity. Diabetes Ther. 2023 Feb;14(2):319-334. doi: 10.1007/s13300-022-01345-6. Epub 2023 Feb 3.
Derived from this study: PubMed 34213819Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
Derived from this study: PubMed 32648108Gallo S, Calle RA, Terra SG, Pong A, Tarasenko L, Raji A. Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials. Diabetes Ther. 2020 Aug;11(8):1849-1860. doi: 10.1007/s13300-020-00867-1. Epub 2020 Jul 9.
Derived from this study: PubMed 32372382Patel S, Hickman A, Frederich R, Johnson S, Huyck S, Mancuso JP, Gantz I, Terra SG. Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials. Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.
Derived from this study: PubMed 32324082Liu J, Tarasenko L, Pong A, Huyck S, Wu L, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Aug;36(8):1277-1284. doi: 10.1080/03007995.2020.1760228. Epub 2020 May 13.
Derived from this study: PubMed 32324065Liu J, Tarasenko L, Pong A, Huyck S, Patel S, Hickman A, Mancuso JP, Ellison MC, Gantz I, Terra SG. Efficacy and safety of ertugliflozin in Hispanic/Latino patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Jul;36(7):1097-1106. doi: 10.1080/03007995.2020.1760227. Epub 2020 May 13.
Derived from this study: PubMed 32236732Cherney DZI, Heerspink HJL, Frederich R, Maldonado M, Liu J, Pong A, Xu ZJ, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Effects of ertugliflozin on renal function over 104 weeks of treatment: a post hoc analysis of two randomised controlled trials. Diabetologia. 2020 Jun;63(6):1128-1140. doi: 10.1007/s00125-020-05133-4. Epub 2020 Mar 31.
Derived from this study: PubMed 31797522Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020 Apr;22(4):574-582. doi: 10.1111/dom.13931. Epub 2020 Jan 3.
Derived from this study: PubMed 31064361Liu J, Pong A, Gallo S, Darekar A, Terra SG. Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials. Cardiovasc Diabetol. 2019 May 7;18(1):59. doi: 10.1186/s12933-019-0856-7.
Derived from this study: PubMed 30614616Gallo S, Charbonnel B, Goldman A, Shi H, Huyck S, Darekar A, Lauring B, Terra SG. Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial. Diabetes Obes Metab. 2019 Apr;21(4):1027-1036. doi: 10.1111/dom.13631. Epub 2019 Feb 14.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Type 2 Diabetes Mellitus

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ertugliflozin 5 mg, Ertugliflozin 15 mg and Glimepiride in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) (time frame: Baseline and Week 26). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02033889, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2018.