Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)

The duration of the trial will be up to approximately 122 weeks. This will include a 1-week screening period, an up to 13-week wash-off/titration/dose stabilization period, a 2-week placebo run-in period, a 104-week double-blind, active comparator-controlled treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug.

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