Efficacy and safety of semaglutide in non-diabetic adults with overweight or obesity: A meta-analysis of randomized controlled trials.

BACKGROUND: Semaglutide has demonstrated significant weight loss benefits, but comprehensive evidence on its long-term efficacy and safety in non-diabetic adults with overweight or obesity remains limited. This meta-analysis provides updated evidence by incorporating oral semaglutide data, extended follow-up duration, and comprehensive subgroup analyses. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases from inception to April 30, 2024. Randomized controlled trials comparing semaglutide with placebo in non-diabetic adults with BMI ≥27 kg/m were included in this study. The Cochrane Risk of Bias 2 tool was used for quality assessment. Data were analyzed using RevMan v5.4. Sensitivity analyses were used to explore the sources of heterogeneity. RESULTS: Seven RCTs involving 5411 participants were included in this review. Semaglutide significantly reduced absolute weight (WMD -12.24 kg, 95 % CI -13.25 to -11.22), percentage weight change (WMD -12.15 %, 95 % CI -13.63 to -10.67), BMI (WMD -4.32 kg/m, 95 % CI -4.75 to -3.89), and waist circumference (WMD -9.32 cm, 95 % CI -9.87 to -8.78). Semaglutide increased likelihood of achieving ≥5 % weight loss (RR 2.63, 95 % CI 2.12-3.25). Total adverse events were modestly but significantly elevated (RR 1.05, 95 % CI 1.01-1.09), primarily gastrointestinal symptoms. Serious adverse reactions were also higher (RR 1.33, 95 % CI 1.08-1.63). CONCLUSIONS: Both oral and subcutaneous semaglutide significantly improve weight management in non-diabetic adults. While the safety profile is generally acceptable, elevated serious adverse events warrant careful patient selection and monitoring. Optimal outcomes occur with lifestyle interventions at doses ≥2.4 mg weekly.