Efficacy of Primary Endoscopic Bariatric and Metabolic Therapies Combined with Anti-Obesity Medications: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic bariatric and metabolic therapies (EBMTs) and anti-obesity medications (AOMs) are effective minimally invasive treatments for obesity. This study aims to compare the safety and efficacy of EBMT combined with AOMs to that of EBMT alone. METHODS: Electronic databases, including PubMed, Medline (Ovid), EMBASE, and the Cochrane Library, were reviewed from inception to August 10, 2025. The primary outcome was percent total weight loss (%TWL) at 12 months. Secondary outcomes included %TWL at 6 months and the rate of serious adverse events. Subgroup analyses by EBMT type and timing of AOM initiation were also performed. RESULTS: Eleven studies comprising 2,609 patients were included, of whom 2,026 (78%) received EBMT alone, and 583 (22%) received EBMT plus an AOM. Combination therapy was associated with significantly greater weight loss compared to EBMT alone (pooled mean difference in %TWL at 12 months of 3.0%; 95% CI, 1.1-4.9; p=0.002). At 12 months, the pooled %TWL was 18.6% (95% CI, 14.0 - 23.2) in the EBMT plus AOM group and 15.6% (95% CI, 11.6 - 19.6) in the EBMT-alone group. This benefit was observed across both intragastric balloon and endoscopic gastric remodeling subgroups. Combination therapy was also associated with greater improvement in diabetes and MASLD. Initiation of AOM after EBMT was associated with greater weight loss than EBMT alone, while initiation prior to EBMT was not. CONCLUSION: EBMT combined with AOM therapy is associated with significantly greater weight loss compared with EBMT alone, with post-EBMT initiation of AOM therapy appearing to be the optimal timing strategy.