Ertugliflozin and Sitagliptin Co-administration Factorial Study (VERTIS FACTORAL, MK-8835-005)

This study will include a 1-week screening period; an up to 12-week metformin titration/dose stabilization period; a 2-week single-blind placebo run-in period; a 52-week (26-week Phase A and 26-week Phase B) double-blind treatment period and a post-treatment telephone contact 14 days after the last dose of study medication.

Inclusion criteria

• Type 2 diabetes mellitus as per American Diabetes Association guidelines
• On metformin monotherapy (>=1500 mg/day) for >=8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy (>=1500 mg/day) for <8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy <1500 mg/day with a Visit 1/Screening A1C >=8.0% and <=11.5% (>=64 mmol/mol and <=102 mmol/mol)
• Body mass index (BMI) >=18.0 kg/m^2
• Male or female not of reproductive potential
• Female of reproductive potential who agrees to remain abstinent from heterosexual activity or to use 2 acceptable combinations of contraception

Exclusion criteria

• History of type 1 diabetes mellitus or ketoacidosis
• History of other specific types of diabetes (e.g., 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 or sitagliptin
• Has been treated with any of the following agents within 12 weeks of study start or during the pre-randomization period: Insulin of any type (except for short-term use [i.e., <=7 days] during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other SGLT2 inhibitors, alpha glucosidase inhibitors or meglitinides, dipeptidyl-peptidase 4 inhibitor (DPP-4 inhibitor), sulfonylureas (SUs), bromocriptine (Cycloset™), colesevelam (Welchol™), any other antihyperglycemic agents (AHA) with the exception of the protocol-approved agents
• Is on a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable prior to study start
• Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable prior to study start
• A 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 start
• Active, obstructive uropathy or indwelling urinary catheter
• History of malignancy <=5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• A known history of human immunodeficiency virus (HIV)
• A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a clinically important hematological disorder (e.g. aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
• A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
• Any clinically significant malabsorption condition
• Current treatment for hyperthyroidism
• On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior study start
• On a previous clinical study with ertugliflozin
• Estimated glomerular filtration rate (eGFR) (using the 4-variable Modification of Diet in Renal Disease Study Equation (MDRD) equation) <60 mL/min/1.73 m^2
• Serum creatinine >= 1.3 mg/dL (115 µmol/L) for males and >= 1.2 mg/dL (106 µmol/L) for females
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times upper limit of normal
• Hemoglobin <12 g/dL (120 g/L) for males and <11 g/dL (110 g/L) for females.
• Participated in other studies involving investigational drug(s) 30 days prior to study start
• Surgical procedure within 6 weeks prior to study start or major surgery planned during the trial
• Positive urine pregnancy test
• Pregnant or breast-feeding, or planning to conceive during the trial, including 14 days following the last dose of study medication
• Planning to undergo hormonal therapy in preparation for egg donation during the trial, including 14 days following the last dose of study medication
• Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking
• Donated blood or blood products within 6 weeks of study start