A Study to Evaluate the Effect of Maridebart Cafraglutide on Insulin Sensitivity and β-cell Function in Participants With Type 2 Diabetes Mellitus

Prior treatment

• One or more episodes of severe hypoglycemia (Level 3 hypoglycemia as defined by the American Diabetes Association classification criteria) within 6 months before screening, as defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery.
• Has modified diet or adopted any nutritional lifestyle modifications within 3 months prior to screening, as assessed by the investigator (or designee) based on participant self-report.
• History of any of the following within 90 days before screening: myocardial infarction, unstable angina, coronary artery bypass graft surgery or other major cardiovascular surgery, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, cerebrovascular accident, or decompensated congestive heart failure, or currently have New York Heart Association Class III or IV heart failure.
• History of acute pancreatitis within 6 months before screening.
• Use within 90 days before randomization of medications, supplements, or alternative remedies for weight loss (eg, GLP-1RA, GIP agonists, phentermine/topiramate, naltrexone/bupropion, orlistat, and sympathomimetic drugs).
• Use within 90 days before randomization of chronic (\> 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations).
• Use within 90 days before randomization of medications that may cause significant weight gain including, but not limited to, atypical antipsychotic and mood stabilizers.
• Currently receiving treatment in another investigational device or drug study, or less than 30 days (or 5 half-lives, whichever is longer) since ending treatment on another investigational device or drug study(ies).
• Major surgical procedure planned during the study.

Other illness

• Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma, or any other type of diabetes mellitus (except T2DM or history of gestational diabetes).
• History of proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy that requires acute treatment.
• History of malignancy within the last 5 years before screening (except nonmelanoma skin cancers, cervical carcinoma in situ, or breast ductal carcinoma in situ).
• Family (first-degree relative\[s\]) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2).
• History or evidence of endocrine disorder (such as Cushing's syndrome) that can cause obesity.
• History of chronic pancreatitis.
• Evidence of hepatitis B or C infection.
• History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or medical monitor, if consulted as necessary, would pose a risk to participant's safety or interfere with the study evaluation, procedures, or completion.

Lab values

• History or evidence of autoimmune disease that can directly or indirectly affect insulin production, insulin action, or glucose metabolism.
• Estimated glomerular filtration rate \< 60 mL/min/1.73 m\^2 calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation at screening.
• Hemoglobin value \< 12 g/dL (males) or \< 10 g/dL (females) at screening or check-in (Day -4).
• Current or prior use of herbal supplements that affect insulin or glucose within 30 days before randomization.

Other

• Positive human immunodeficiency virus test at screening.
• Participants of childbearing potential unwilling to adhere to contraception requirements during treatment and for an additional 16 weeks after the last dose of IMP.
• Participants who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of IMP.
• Participants planning to become pregnant while on study through 16 weeks after the last dose of IMP.
• Participant has known sensitivity to any of the products or components to be administered during dosing.
• Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.

• Informed consent before initiation of any study-specific activities/procedures.
• Male or female participants aged ≥ 18 and ≤ 70 years at the time of signing informed consent.
• Body mass index ≥ 23.0 kg/m\^2 (Asian participants only) or ≥ 25 and ≤ 45 kg/m\^2 at screening.
• Diagnosis of T2DM at least 6 months before screening based on the WHO classification.
• Treatment of T2DM for at least 3 months prior to screening with diet and exercise and a stable dose of metformin (either immediate release or extended release), with or without a stable dose of 1 additional OAM other than metformin.