Comparison of Efficacy, Safety, and Tolerability of ITCA 650 to Empagliflozin and Glimepiride as add-on Metformin

Inclusion Criteria:

- Diagnosis of T2D 3 months prior to the Screening Visit.

- Body mass index (BMI) between ≥25 to ≤45 kg/m2 at the Screening Visit.

- Glycosylated hemoglobin A1c (HbA1c) ≥7.5 and ≤10.5%. 5. 6. On a stable (3 months prior
to the Screening Visit) treatment regimen of metformin monotherapy of ≥1500 mg/day).

Exclusion Criteria:

- History of type 1 diabetes.

- Prior participation in a clinical study involving ITCA 650.

- Treatment with any GLP-1 receptor agonist (eg, liraglutide, exenatide) within 6 months
prior to Screening.

- History or evidence, within the last 6 months prior to the Screening Visit, of
myocardial infarction, coronary revascularization (coronary artery bypass grafting or
percutaneous coronary intervention), unstable angina, or cerebrovascular accident or
stroke.

- History or evidence of acute or chronic pancreatitis.

- History of medullary thyroid cancer or a family or personal history of multiple
endocrine neoplasia type 2.

- Treatment of medications that affect GI motility.

- History of hypersensitivity to exenatide, empagliflozin, or glimepiride or to one of
its excipients.

- Women that are pregnant, lactating, or planning to become pregnant.

- Chronic (>10 consecutive days) treatment with systemic corticosteroids within 8 weeks
prior to screening.