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

Inclusion Criteria:

• Have been diagnosed with Type 2 Diabetes Mellitus (T2DM) for at least 6 months priorto screening.

• Treated with diet and exercise and metformin daily, with or without other allowedoral antihyperglycaemia medications (OAMs), 3 months prior to screening. AllowedOAMs are dipeptidyl peptidase-4 inhibitors (DPP-IV) inhibitors, sodium/glucosecotransporter 2 (SGLT2) inhibitors, glinides, and sulfonylureas.

• Have a HbA1c value at screening of:

• 6.5% and ≤ 9.5 % if on metformin with or without SGLT2 inhibitors, or

• 6% and ≤8.5% if on metformin in combination with allowed OAMs that requirewashout.

• Have venous access sufficient to allow for blood sampling as per the protocol.

• Have clinical laboratory test results within normal reference range for thepopulation or investigative site or results with acceptable deviations that arejudged to be not clinically significant by the investigator.

• Have a body mass index (BMI) between 25 kilograms per meter squared (kg/m²) and 45kg/m², both inclusive, at screening.

• Have had a stable body weight that is less than 5% change during the 3-month periodprior to screening.

Exclusion Criteria:

• Have Type 1 Diabetes Mellitus (T1DM)

• Have had more than 1 episode of severe hypoglycaemia, as defined by the AmericanDiabetes Association criteria, within 6 months before screening or a history ofhypoglycaemia unawareness or poor recognition of hypoglycaemic symptoms; anyparticipant that cannot communicate an understanding of hypoglycaemic symptoms andthe appropriate treatment of hypoglycaemia prior to the first dose of study drugshould also be excluded.

• Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma requiringhospitalisation 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 orcorticosteroids, focal/grid macular laser surgery, panretinal photocoagulation, orvitrectomy for diabetic retinopathy at screening.

• Have impaired renal estimated glomerular filtration rate <60.0 mL/min/1.73 m²calculated 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'ssyndrome), or

• Alkaline phosphatase (ALP) level ≥1.5X ULN

• Show evidence of possible chronic or active hepatitis B, including hepatitis B coreantibody and/or hepatitis B surface antigen positivity.

• Have a positive Hepatitis C virus (HCV) antibody (Ab) test. Participants with apositive HCV Ab test at screening can be included only if a confirmatory HCVribonucleic acid (RNA) test is negative.

• Have a known clinically significant gastric emptying abnormality, have undergonegastric bypass (bariatric) surgery or restrictive bariatric surgery or chronicallytake 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 theinvestigator.

• Have a 12-lead ECG abnormality at screening that, in the opinion of theinvestigator, increases the risks associated with participating in the study or mayconfound electrocardiogram (ECG) data analysis.

• Have a personal or family history of medullary thyroid carcinoma (MTC) or multipleendocrine neoplasia syndrome Type 2 (MEN 2).

• Have an active or untreated malignancy or have been in remission from a clinicallysignificant malignancy for <5 years prior to screening. Exceptions:

• basal cell or squamous epithelial carcinomas of the skin that have beenresected with no evidence of metastatic disease for 3 years

• cervical carcinoma in situ, with no evidence of recurrence within the 5 yearsprior to baseline, or

• in situ prostate cancer.

• Have, in the opinion of the investigator, evidence of significant, uncontrolledendocrine 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, anytime within the 3 months prior to screening.

• Have taken prescribed or over-the-counter (OTC) medications, either approved orunapproved, 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 humanHIV antibodies.

• Have a calcitonin level at screening of ≥35.0 nanograms per liter (ng/L), [≥35.0picograms per milliliter (pg/mL)].