Comparison of pharmacotherapies for obesity with sleeve gastrectomy: a network meta-analysis and systematic review.

INTRODUCTION: Tirzepatide, a glucagon-like peptide-1 receptor agonist (GLP1RA) and glucose-dependent insulinotropic-peptide (GIP), has shown efficacy regarding weight-loss. METHODS: Systematic review and network meta-analysis of randomized controlled trials. MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched between 2014 and 2024 for trials comparing sleeve gastrectomy (SG), Tirzepatide and other pharmacotherapies to control or each other. Eligible studies: adults with obesity and weight loss outcomes ≥24 weeks. Primary outcome: percentage change total body weight. Secondary outcomes included adverse events. Pairwise and network meta-analyses were performed. Interventions ranked by: P-score, mean difference (MD), 95% confidence intervals (CI). RESULTS: Data from 23 trials (14,293 participants) were analyzed. SG (MD 21.1% TWL, 95% CI 14.2% to 28.0%) and Tirzepatide 10 or 15 mg (MD 21.3% TWL, 95% CI 17.3% to 25.2%) demonstrated statistically equivalent weight-loss efficacy (P-score: 0.84) and had the most favorable effectiveness profiles. Semaglutide 2.4 mg (MD 12.7% TWL) and Liraglutide 3.0 mg (MD 5.1% TWL) showed moderate efficacy, whilst Orlistat showed minimal effect (MD 2.7% TWL, 95% CI -4.2% to 9.6%). Network meta-analysis of adverse events demonstrated that Semaglutide 2.4 mg and Orlistat had the most favorable safety profiles amongst pharmacotherapies. CONCLUSIONS: Tirzepatide 10 mg and 15 mg is equivalent to SG regarding weight-loss efficacy. REGISTRATION: This paper was registered with PROSPERO (ID: CRD420251016726). Due to institutional academic requirements and checks, registration was completed after the review began, however the review protocol (supplement material S1) was developed prior to the review, provided by the authors, and thoroughly adhered to by the authors.