This is a study of retatrutide in participants with obesity. The main purpose is to learn more about how retatrutide maintains body weight loss. The study will have two treatment phases: an 80 week lead-in phase in which all participants will take retatrutide dose 1 and a 36 week randomized, double-blinded phase in which participants will either take retatrutide dose 1, retatrutide dose 2, or switch to placebo. Participation in the study will last around 125 weeks.

Inclusion Criteria:

• Have obesity and a history of at least one self-reported unsuccessful dietary effort to reduce body weight

Exclusion Criteria:

• Have a self-reported change in body weight >5 kilograms (kg) (11 pounds) within 90 days before screening

• Have a prior or planned surgical treatment for obesity

• Have a prior or planned endoscopic procedure and/or device-based therapy for obesity

• Have Type 1 Diabetes, Type 2 Diabetes, or any other type of diabetes

• Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)

• Have had within the past 90 days before screening:

  • acute myocardial infarction
  • cerebrovascular accident (stroke)
  • hospitalization for unstable angina, or
  • hospitalization due to congestive heart failure

• Have New York Heart Association Functional Classification Class IV congestive heart failure

• Have a history of chronic or acute pancreatitis

• Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.