Abstract:
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 in adults with overweight and obesity with or without type 2 diabetes (T2DM) on major adverse cardiovascular events (MACE), heart failure (HF), and all-cause mortality.
Methods: We searched MEDLINE, Embase, and the Cochrane Library from inception of each database to June 30, 2024 for randomized controlled trials (RCTs) including adults over age 18 years with overweight and obesity who received intensive lifestyle and dietary modification, obesity pharmacotherapy, or bariatric/metabolic surgery. Six pairs of reviewers screened titles/abstracts and full-texts and extracted study-level data. Two reviewers independently conducted risk of bias (RoB) assessments using the Cochrane RoB 2 tool. We conducted pairwise meta-analyses with comparisons to active comparator or placebo. We performed random-effects NMA for each critical outcome. We assessed certainty of evidence using the Confidence in Network Meta-analysis (CINeMA) tool. We performed subgroup analysis of studies for participants without diabetes, sensitivity analysis of studies limited to overall lowest RoB, and meta-regression for age, sex, race, BMI, prior CV disease, diabetes prevalence, study duration, and publication year to explore for heterogeneity. Finally, we evaluated dose-responses for clinically relevant doses of liraglutide, semaglutide, and tirzepatide.
Results: We screened 13,362 unique titles and abstracts and included 67 RCTs, encompassing 205,889 participants with mean percentage 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 overall 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 the 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), showed the 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 the 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.
