Clinical trial NCT02630706 (phase 3, status: completed)
Conditions: type 2 diabetes mellitus
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: ertugliflozin 5 mg, ertugliflozin 15 mg, placebo matching ertugliflozin, metformin, glimepiride
SMILES: CCOC1=CC=C(CC2=CC(=CC=C2Cl)[C@]23OC[C@](CO)(O2)[C@@H](O)[C@H](O)[C@H]3O)C=C1, CCOC1=CC=C(CC2=CC(=CC=C2Cl)[C@]23OC[C@](CO)(O2)[C@@H](O)[C@H](O)[C@H]3O)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CSCC[C@H](N)C(O)=O, [H][C@]1(C)CC[C@@]([H])(CC1)N=C(O)NS(=O)(=O)C1=CC=C(CCN=C(O)N2CC(C)=C(CC)C2=O)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Asian participants ≥18 years of age at the time of initial Screening.

          -  Type 2 diabetes mellitus as per American Diabetes Association guidelines.

          -  Metformin monotherapy (≥1500 mg/day) with an initial Screening A1C of 7.0-10.5% (53-91
             mmol/mol) OR metformin monotherapy (<1500 mg/day) with an initial Screening A1C of
             7.5-11.0% (58-97 mmol/mol) OR dual combination therapy with metformin + sulfonylurea,
             dipeptidyl peptidase-4 (DDP-4) inhibitor, meglitinide, or alpha-glucosidase inhibitor
             with an initial Screening A1C of 6.5-9.5% (48-80 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 a history of 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.)

          -  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.

          -  Mean value for triplicate screening sitting systolic blood pressure >160 mm Hg and/or
             diastolic blood pressure >90 mm Hg after at least a 5-minute seated rest at screening

          -  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.

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or
             engages in binge drinking.

          -  Any clinically significant malabsorption condition.

          -  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 known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2)
             inhibitor.

          -  On a previous clinical study with ertugliflozin.

          -  Is taking blood pressure or lipid altering medications that have not been on a stable
             dose for at least 4 weeks prior to study start.

          -  Current treatment for hyperthyroidism.

          -  Male participants with a serum creatinine >=1.3 mg/dL (>=115 mol/L) or female
             participants with a serum creatinine >=1.2 mg/dL (>=106 mol/L) or participants with an
             estimated glomerular filtration rate (eGFR) <55 mL/min/1.73m^2 according to the
             4-variable Modification of Diet in Renal Disease (MDRD) equation at screening.

          -  An aspartate transaminase (AST) or alanine transaminase (ALT) >2X the upper limit of
             normal (ULN) range at screening, or a total bilirubin >1.5 X the ULN unless the
             participant has a history of Gilbert's.

          -  On thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
             prior to study start.

          -  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.

          -  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
             during concomitant illness or other stress), other injectable anti-hyperglycemic
             agents (e.g., pramlintide, exenatide, liraglutide), another SGLT2 inhibitor,
             bromocriptine, colesevelam, rosiglitazone or pioglitazone, or any other AHA with the
             exception of the protocol-approved agents.

          -  Is on or likely to require treatment ≥14 consecutive days or repeated courses of
             pharmacologic doses of corticosteroids.

          -  Has undergone a surgical procedure within 6 weeks prior to study start or has planned
             major surgery during the study.

          -  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.

          -  Donated blood or blood products within 6 weeks of study start.

          -  Has Human Immunodeficiency Virus (HIV).

          -  Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells.

          -  Has clinically important hematological disorders (such as aplastic anemia,
             myeloproliferative or myelodyplastic syndromes, thrombocytopenia.)