Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin 5 mg; Ertugliflozin 10 mg; Glimerpiride; Placebo to Ertugliflozin; Placebo to Glimepiride; Metformin; Sitagliptin
Intervention description: Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104; Ertugliflozin, 10 mg, oral, once daily from Day 1 to Week 104.; Glimepiride, oral tablets, initiated at 1 mg daily and titrated up to the maximum approved dose (8 mg daily based on the local country label) or maximum tolerated dose; Matching placebo to ertugliflozin, 5 mg and/or 10 mg, oral, once daily, from Day 1 to Week 104; Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.; Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. Participants on metformin <1500 at screening are up-titrated to >= 1500 daily.; Open label, oral, once daily, rescue medication as required.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Glimepiride; Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1326.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy and safety of the addition of ertugliflozin
      (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who
      have inadequate glycemic control on metformin. The primary hypothesis of this study is that
      after 52 weeks, the change from baseline in hemoglobin A1c (A1C) in participants treated with
      the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in
      participants treated with the addition of glimepiride.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of T2DM in accordance to American Diabetes Association guidelines

          -  On metformin monotherapy or metformin in combination with a single allowable
             anti-hyperglycemic agent (AHA), DPP-4 inhibitors, meglitinides and AGIs are listed as
             allowable AHAs along with sulfonylureas prior to study participation.

          -  Body Mass Index (BMI) ≥18.0 kg/m^2

          -  Male or female not of reproductive potential

          -  If a female of reproductive potential, agree to remain abstinent or to use (or have
             their partner use) 2 acceptable combinations of birth control while participating in
             the trial and for 14 days after the last use of study drug.

        Exclusion Criteria:

          -  History or presence of type 1 diabetes mellitus or a history of ketoacidosis

          -  History of other specific types of diabetes (eg, genetic syndromes, secondary
             pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and
             post-organ transplant).

          -  A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2)
             inhibitor

          -  Use of the following prohibited therapeutic agents within 12 weeks of study
             participation: insulin, injectable anti-hyperglycemic agents, pioglitazone or
             rosiglitazone, another SGLT2 inhibitor, bromocriptine (Cycloset®), colesevelam
             (Welchol®), and any other non-approved anti-hyperglycemic therapy

          -  Known hypersensitivity or intolerance to metformin or glimepiride

          -  On a weight-loss program or medication or medication associated with weight changes
             and is not weight-stable (>=5% change in body weight in the last 6 months)

          -  History of bariatric surgery less than 12 months prior to study participation

          -  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

          -  Active, obstructive uropathy or an indwelling urinary catheter

          -  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

          -  Known history of Human Immunodeficiency Virus (HIV)

          -  Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells

          -  A medical history of active liver disease (other than non-alcoholic hepatic
             steatosis), including chronic active hepatitis B or C (assessed by medical history),
             primary biliary cirrhosis, or symptomatic gallbladder disease

          -  Any clinically significant malabsorption condition

          -  Being treated for hyperthyroidism, or on thyroid replacement therapy that has not been
             at a stable dose for at least 6 weeks prior to study participation

          -  Previous randomization in a study with ertugliflozin

          -  Participation in other studies involving investigational drug(s) within 30 days of
             study participation and/or during the pre-randomization period

          -  A surgical procedure within 6 weeks prior to study participation or planned major
             surgery during the trial

          -  A positive urine pregnancy test

          -  Pregnant or breast-feeding, or expecting to conceive during the trial, including 14
             days following the last dose of study drug

          -  Undergoing hormonal therapy in preparation to donate eggs during the period of the
             trial, including 14 days following the last dose of study drug

          -  Consumption of more than 2 alcoholic drinks per day or engages in binge drinking

          -  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