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

Jan 24, 2026European journal of pharmacology

Effectiveness and safety of semaglutide in non-diabetic adults with overweight or obesity: a combined analysis of clinical trials

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Abstract

Semaglutide led to a significant average weight reduction of 12.24 kg in non-diabetic adults with overweight or obesity.

Participants in the study experienced a percentage weight change of -12.15%.
Body Mass Index (BMI) reduced by an average of -4.32 kg/m².
Waist circumference decreased by an average of -9.32 cm.
The likelihood of achieving at least a 5% weight loss increased by 2.63 times.
Total adverse events were modestly elevated, mainly gastrointestinal symptoms.
The rate of serious adverse reactions was significantly higher, with a relative risk of 1.33.

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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/mwere 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. 2

RESULTS: Seven RCTs involving 5,411 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). 2

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.

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

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