Effect of semaglutide with obesity or overweight individuals without diabetes: an Umbrella review of systematic reviews.

OBJECTIVE: Summarize the effectiveness and safety of Semaglutide for non-diabetic obese patients through umbrella analysis. METHODS: From inception to May 2024, we searched PubMed, EMbase, Web of Science, and The Cochrane Library for a systematic review and meta-analysis of semaglutide in non-diabetic obesity. AMSTAR-2 assessed review quality, ROB scrutinized RCT quality, and RCTs were selected based on overlap. Random-effects meta-analysis synthesized data on weight, waist, BMI, ect. RESULTS: The study encompassed 7 reviews and 10 RCTs, revealing that semaglutide induced average weight loss 11.71 kg [-13.16, -10.26] in non-diabetic obese patients, a 12.79% reduction [-14.4, -11.18]. Notably, ≥5, ≥10, ≥15, and ≥20% weight-loss rates significantly increased. Semaglutide also reduced waist by 9.39 cm [-10, -8.79], BMI by 4.27 kg/m^2 [-4.78, -3.75], SBP by 4.78 mmHg [-5.63, -3.93], DBP by 2.56 mmHg [-3.96, -1.17], and lipids by 3.2 mmol/l [-5.65, -0.75]. FBG significantly dropped by 5.46 mmol/l [-8.99, -1.93], and SF-36 scores improved by 1.7 points [0.78, 2.63]. However, common adverse reactions included nausea [RR: 2.59], diarrhea [RR: 1.77], and constipation [RR: 2.07]. CONCLUSIONS: Semaglutide shows significant weight loss and health benefits in non-diabetic obesity. However, Recent studies show semaglutide can cause NAION and erectile dysfunction, beyond previously reported adverse reactions. Besides, High overlap in current research highlights a lack of RCTs. And there is a high degree of heterogeneity across included studies. More large-scale, rigorous RCTs are needed to assess safety and support clinical use. REGISTER: The study was registered at PROSPERO on 24 December 2023 (registration number:CRD42023493235).