Efficacy and Safety of Pharmacological, Endoscopic, and Surgical Treatments for Obesity: A GRADE-Based Network Meta-Analysis

Objective: This review compared antiobesity strategies—obesity management medications (OMM), endoscopic bariatric procedures (EBP), and metabolic bariatric surgery (MBS)—with lifestyle intervention, placebo, or no therapy (LSI/Pbo/NT). Methods: This network meta-analysis included randomized clinical trials comparing OMM, EBP, and MBS versus LSI/Pbo/NT or active comparators in adults with obesity. MEDLINE and Embase were searched up to December 1, 2024. The primary endpoint was total body weight loss percentage (TBWL%), analyzed at 26–52, 53–104, 105–156, and ≥ 156 weeks. This study was registered with PROSPERO (CRD42024623707). Results: Of 139 RCTs, 54 evaluated MBS (n = 61,961), 21 EBP (n = 2934), and 64 OMM (n = 5991). At 26–52 weeks, most treatments showed significant effects versus the reference. TBWL% exceeded 10% with most surgeries and tirzepatide. Long-term data were lacking for most OMM and all EBP. Most treatments maintained their efficacy over time, except greater curvature plication. EBP and MBS were generally associated with a higher SAE risk than OMM; BPD showed the highest long-term SAE incidence. Conclusions: MBS appears superior in the long term (particularly for higher-efficacy procedures, such as RYGB, SG, SADI, and BPD). EBP, except ESG, was less effective than newer OMM. Semaglutide and tirzepatide showed no inferior short-term results in comparison with MBS.