A Study to Evaluate the Effect of Retatrutide on Insulin Secretion and Insulin Sensitivity in Adult Participants With Type 2 Diabetes Mellitus

Exclusion Criteria35

• Have Type 1 Diabetes Mellitus (T1DM)
• Have had more than 1 episode of severe hypoglycaemia, as defined by the American Diabetes Association criteria, within 6 months before screening or a history of hypoglycaemia unawareness or poor recognition of hypoglycaemic symptoms; any participant that cannot communicate an understanding of hypoglycaemic symptoms and the appropriate treatment of hypoglycaemia prior to the first dose of study drug should also be excluded.
• Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma requiring hospitalisation within the 6 months prior to screening.
• Are currently receiving, planning to receive, or in need of treatment, that is, intravitreal injections of Vascular Endothelial Growth Factor inhibitor or corticosteroids, focal/grid macular laser surgery, panretinal photocoagulation, or vitrectomy for diabetic retinopathy at screening.
• Have impaired renal estimated glomerular filtration rate \<60.0 mL/min/1.73 m² calculated by Chronic Kidney Disease-Epidemiology (2021).
• Have acute or chronic pancreatitis or a history of acute idiopathic pancreatitis.
• Have elevations in:
• serum aspartate aminotransferase (AST) \>2.5X the upper limit of normal (ULN)
• serum alanine aminotransferase (ALT) \>2.5X ULN
• total bilirubin level (TBL) \>1.5X ULN (except, participants with Gilbert's syndrome), or
• Alkaline phosphatase (ALP) level ≥1.5X ULN
• Show evidence of possible chronic or active hepatitis B, including hepatitis B core antibody and/or hepatitis B surface antigen positivity.
• Have a positive Hepatitis C virus (HCV) antibody (Ab) test. Participants with a positive HCV Ab test at screening can be included only if a confirmatory HCV ribonucleic acid (RNA) test is negative.
• Have a known clinically significant gastric emptying abnormality, have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery or chronically take drugs that directly affect GI motility.
• Have had within 3 months prior to screening:
• acute myocardial infarction
• congestive heart failure New York Heart Association (NYHA) class III or IV, and/or
• cerebrovascular accident \[stroke\]
• coronary artery revascularisation
• hospitalization hospitalisation for unstable angina
• hospitalization hospitalisation due to congestive heart failure.
• Have a history of additional risk factors for Torsades de Pointes (for example, heart failure, hypokalaemia, family history of Long QT Syndrome), as judged by the investigator.
• Have a 12-lead ECG abnormality at screening that, in the opinion of the investigator, increases the risks associated with participating in the study or may confound electrocardiogram (ECG) data analysis.
• Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome Type 2 (MEN 2).
• Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for \<5 years prior to screening. Exceptions:
• basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
• cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline, or
• in situ prostate cancer.
• Have, in the opinion of the investigator, evidence of significant, uncontrolled endocrine abnormality, for example, thyrotoxicosis or adrenal crisis.
• Have a prior or planned surgical treatment for obesity.
• Have a prior or planned endoscopic and/or device-based therapy for obesity.
• Have taken any glucose-lowering medications other than metformin, DPP IV inhibitors, sulfonylureas and/or SGLT-2 inhibitors, regardless of the indication for use, any time within the 3 months prior to screening.
• Have taken prescribed or over-the-counter (OTC) medications, either approved or unapproved, or alternative remedies, including herbal or nutritional supplements, intended to promote body weight reduction, within 3 months prior to screening.
• Have evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies.
• Have a calcitonin level at screening of ≥35.0 nanograms per liter (ng/L), \[≥35.0 picograms per milliliter (pg/mL)\].