Quality and sustainability of weight loss with injectable incretin therapies in adults with obesity: an umbrella review of systematic reviews and meta analyses

Resumen

Objective: To synthesize evidence from systematic reviews on the magnitude and sustainability of weight loss with injectable incretin therapies in adults with obesity, including weight regain after discontinuation, body composition, quality of life, and safety. Methodology: An umbrella review was conducted according to PRIOR, PRISMA 2020, and Joanna Briggs Institute guidance. PubMed, the Cochrane Library, Epistemonikos, and Google Scholar were searched through July 23, 2026. Systematic reviews with or without meta analysis addressing liraglutide, semaglutide, tirzepatide, retatrutide, or related incretin agonists were eligible. Methodological quality was appraised with AMSTAR 2. Because primary trials overlapped substantially, estimates were not statistically recombined. Results: Eighteen reviews were included. Representative estimates showed mean placebo corrected weight reductions of 4.72% with liraglutide, 10.73% with semaglutide, and 16.03% with tirzepatide; retatrutide reached 22.1% in a still limited evidence base. Discontinuation was followed by clinically relevant regain, commonly exceeding 5 kg, with faster regain after larger initial losses. About one quarter of total weight reduction reflected lean mass in body composition analyses. Gastrointestinal events increased treatment withdrawal, whereas serious events remained uncommon. Conclusion: Injectable incretin therapies produce substantial weight loss, but the quality and durability of benefit depend on continued treatment, muscle preservation, tolerability, and explicit maintenance planning.