This trial is a multi-center, adaptive, randomized, double-blind, placebo- and active- controlled, parallel group, Phase 2 study in subjects with T2DM to evaluate the effect of TTP399 on HbA1c following administration for 6 months.

Inclusion Criteria:

• A historical diagnosis of Type 2 Diabetes in accordance with the American Diabetes Association (ADA) guidelines, with diagnosis at least 6 months prior to Screening.
• On a stable (for the last 3 months prior to screening) regimen of metformin monotherapy equivalent of at least 1000 mg once daily.
• Males, females of childbearing potential (must have a negative pregnancy test and be willing to comply with protocol contraception), and females of non-childbearing potential.
• Age 18 to 75 years, inclusive, at the time of screening.
• HbA1c ≥7.0% and ≤9.5%.
• Generally stable health without active infection or history of major surgery or significant injuries within the last year.

Exclusion Criteria:

• Diagnosis of Type 1 diabetes mellitus, maturity-onset diabetes of the young, insulin-requiring Type 2 Diabetes, other unusual or rare forms of diabetes mellitus, or history of diabetic ketoacidosis.
• Clinically significant abnormal lab values including eGFR <50ml/min/1.73m2, ALT, bilirubin or AST >1.5 X ULN, hypokalemia or other clinically significant electrolyte abnormality.
• History of myocardial infarction, unstable angina, coronary revascularization, stroke, or transient ischemic attack within 2 years of screening.
• Presence of symptomatic congestive heart failure.
• History of cardiac arrhythmias requiring treatment or prophylaxis with drugs or devices during the last 2 years or any history of atrial fibrillation or flutter beyond a single short-term episode (e.g., lasting 1-2 days).
• History or presence of a 2nd degree or greater atrioventricular block in the absence of a pacemaker.
• A 12-lead ECG, from screening or baseline demonstrating QTcF interval >450 msec for males or >47 msec for females.
• A family or personal history of long QT syndrome.
• History of pancreatitis.
• Persistent, uncontrolled hypertension.
• Presence of chronic active hepatitis (hepatitis B, hepatitis C, nonalcoholic steatohepatitis [NASH]) and/or known liver cirrhosis.
• Participation in any formal weight loss program, or fluctuation of > 5% in body weight, or having received medications approved for weight loss within 3 months prior to screening.
• A positive pre-study drug screen.
• Participation in a clinical trial and receipt of an investigational product within 30 days.
• Have a history of drug abuse within 2 years of screening or a positive pre-screen drug screen.
• Have a history of hypoglycemic episode requiring glucose, glucagon, or orange juice administered by someone other than the patient within 6 months prior to screening.
• A history of excessive alcohol consumption within the last 2 years prior to screening
• Mental or legal incapacitation.
• Blood donation of approximately 1 pint (500 mL) within 8 weeks.
• History of MEN-2 or family history of medullary thyroid cancer.
• History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior study start.