The primary objective of this trial is to evaluate the long-term efficacy, safety, and tolerability of maridebart cafraglutide in participants with obesity or overweight. Trial 20250197 is an extension of trial 20210181 (NCT06858839).

Inclusion Criteria:

• Signed informed consent form (ICF) which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Completed the parent trial (2010181)
• Completed week 72 visit in parent trial
• Did not permanently discontinue trial intervention in parent trial
• Randomized within 7 Days of week 72 visit in the parent trial
• Participants must use protocol-specified contraception during treatment, and for an additional 16 weeks after the last dose of trial intervention

Exclusion Criteria:

• Planned (during the trial) surgical, endoscopic, or device-based treatment for obesity
• Body mass index ≤ 18.5 kilograms per meter square (kg/m^2)
• Participant has known sensitivity to any of the products or components to be administered during dosing
• History of ischemic optic neuropathy
• Any malignancy diagnosed during parent trial (20210181) except for the following treated with curative intent: nonmelanoma skin cancers, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ.
• Newly identified (i.e., identified during 20210181) multiple endocrine neoplasia syndrome type 2 or family (first-degree relative[s]) history of medullary thyroid cancer.
• Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at week 72 visit from parent trial before randomization
• Any suicidal ideation of category 4 or 5 OR any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) Since Last Visit version at week 72 visit from parent trial before randomization.
• Participant unlikely to be able to complete all protocol-required procedures, restrictions and requirements, in the judgment of the individual and investigator.
• History or evidence of any other clinically significant disorder, condition, or disease (including, but not limited to known drug or alcohol abuse, eating disorders, and conditions identified during the parent trial) that, in the opinion of the investigator, would pose a risk to participant safety.
• Currently pregnant (confirmed with positive pregnancy test) or breastfeeding or
• Planning to become pregnant or breastfeed while on trial until an additional 16 weeks after the last dose of trial intervention.
• Major surgical procedures planned during the trial.
• Participants with minor surgical procedures (not requiring general anesthesia or deep sedation) planned during the trial may be eligible at the discretion of the investigator.
• Investigative site personnel directly affiliated with the trial and/or their immediate family (ie, spouse, parent, child, or sibling, whether biological or legally adopted).

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s).In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.