Clinical trial NCT02099110 (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: matching placebo to ertugliflozin 5 mg, matching placebo to ertugliflozin 10 mg, matching placebo to sitagliptin 100 mg, ertugliflozin 5 mg, ertugliflozin 10 mg, sitagliptin 100 mg, metformin >= 1500 mg/day, glimepiride rescue medication
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, 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, N[C@@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F, CN(C)C(=N)NC(N)=N, [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:

          -  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