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These trials have scrutinized its efficacy and safety compared to other GLP-1 agonists

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History of gestational diabetes is permitted Previous bariatric surgery or planned bariatric surgery History of hypertrophic cardiomyopathy Abnormal electrocardiogram (ECG) findings at screening that meet Cornell voltage criteria for left ventricular hypertrophy Any malignancy in the past 5 years prior to screening (except for nonmelanoma skin cancer that has been resected with no evidence of metastatic disease for 3 years prior to screening) History of poorly controlled hypertension, as defined in the protocol Have a history of any other condition (such as known drug abuse, alcohol abuse, diagnosed eating disorder, or a severe mental illness) that, in the opinion of the investigator, may preclude the participant from following and completing the protocol Have history of use of marijuana/tetrahydrocannabinol (THC) within 90 days prior to Visit 1 of enrollment and are unwilling to abstain from marijuana/THC use during the trial Has a history of any neuromuscular disorder (eg, multiple sclerosis, myasthenia gravis, myopathy, peripheral neuropathy, etc) Note: Other protocol-defined Inclusion/ Exclusion Criteria apply Trial design 1,005 participants in 13 patient groups, including a placebo group Placebo Treatment: Drug: Matching Placebo-Part A Trevogrumab Treatment: Drug: Trevogrumab-Part A Arm A0 Part B Semaglutide (sema) and subcutaneous (SC) placebo and intravenous (IV) placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Matching Placebo-Garetosmab Drug: Matching Placebo-Trevogrumab Arm A1 Part B Sema and SC placebo and IV placebo followed by high dose trevogrumab (trevo) Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Matching Placebo-Garetosmab Drug: Matching Placebo-Trevogrumab Arm B0 Part B Sema, moderate-high dose trevo, and IV placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Matching Placebo-Garetosmab Drug: Matching Placebo-Trevogrumab Arm B1 Part B Sema, moderate-high dose trevo, and IV placebo followed by high dose trevo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Matching Placebo-Garetosmab Arm C0 Part B Sema, high dose trevo, and IV placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Matching Placebo-Garetosmab Drug: Matching Placebo-Trevogrumab Arm C1 Part B Sema, high dose trevo, and IV placebo followed by high dose trevo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Matching Placebo-Garetosmab Arm D0 Part B Sema, high dose trevo, and garetosmab (gareto) followed by SC placebo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Garetosmab Drug: Matching Placebo-Trevogrumab Arm D1 Part B Sema, high dose trevo, and gareto followed by high dose trevo Randomized 1:1:1:1:1:1:1:1 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Garetosmab Arm 1 Part C Sema and SC placebo Randomized 1:2:2 Treatment: Drug: Semaglutide Drug: Matching Placebo-Trevogrumab Arm 2 Part C Sema and SC low dose trevo Randomized 1:2:2 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Drug: Matching Placebo-Trevogrumab Arm 3 Part C Sema and SC moderate dose trevo Randomized 1:2:2 Treatment: Drug: Semaglutide Drug: Trevogrumab-Part B and Part C Trial contacts and locations 68 Loading