3089-LB: Comparative Efficacy of Obesity Treatments on Major Adverse Cardiovascular Events, Heart Failure, and All-Cause Mortality in Adults with Overweight and Obesity: A Systematic Review and Network Meta-analysis

Introduction and Objective: Obesity is a chronic multi-system disease that impacts cardiovascular (CV) morbidity and mortality. The objective of this systematic review with network meta-analysis (NMA) was to determine the efficacy of obesity treatments on major adverse cardiovascular events (MACE), heart failure (HF), and all-cause mortality. Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to June 30, 2024 for RCTs in adults >= 18 years with obesity who received intensive lifestyle modification, pharmacotherapy, or bariatric surgery. Six pairs of reviewers screened titles/abstracts, full-texts, extracted study-level data, and conducted risk of bias (RoB) with Cochrane RoB 2 tool. We conducted pairwise meta-analyses with comparisons to active comparator or placebo. We performed frequentist random-effects NMA for each critical outcome and reported confidence with the CINeMA tool. Results: We included 67 RCTs, encompassing 205,889 participants with mean female 47.7% (SD 16.4), mean age 63.53 years (SD 0.42), and mean BMI 32.6 kg/m2 (SD 0.14). The NMA showed that compared to placebo, metformin (OR 0.63; 95% CI: 0.32-1.22; p-score=0.83), tirzepatide (OR 0.71; 95% CI: 0.41-1.23; p-score=0.73), and canagliflozin (OR 0.72; 95% CI 0.56-0.93; p-score=0.78) had lowest odds of MACE; bariatric surgery (OR 0.24; 95% CI 0.03-1.70; p-score=0.89), sotagliflozin (OR 0.50; 0.36-0.69; p-score=0.87), and tirzepatide (OR 0.55; 95% CI 0.33-0.92; p-score=0.80), had lowest odds of HF; sotagliflozin (OR 0.50; 95% CI: 0.40-0.63;p-score=0.98), empagliflozin (OR 0.69; 95% CI 0.62-0.76; p-score=0.88), and metformin (OR 0.79; 95% CI 0.35-1.75; p-score=0.63) had lowest odds of mortality. Conclusion: This is the first NMA to compare obesity treatments on CV outcomes. These findings underscore the importance of tailoring obesity treatments to prevent CV outcomes and provide personalized outcomes-focused obesity care. Disclosure S. Sarma: None. S. Straus: None. A. Veroniki: None. P. Bapat: None. M. Jay: None. A. Alsefaou: None. S. Cho: None. D. Davoudi: None. P. Esemu-Ezewu: None. O.A. Iyekekpolor: None. S. Kambo: None. M. Maher: None. M. Malik: None. S. Nannapaneni: None. A. Sami: None. L. Jaakkimainen: None. A. Weisman: None. L. Lipscombe: None. Funding Clinician Investigator Program, University of Toronto Clinician Scientist Training Program, University of TorontoDr.