Effects of subcutaneous semaglutide on weight loss and inflammatory markers in adults with overweight or obesity without diabetes: a systematic review and meta-analysis

Background/Objectives: Obesity is a chronic, relapsing disease associated with multiple serious comorbidities. Semaglutide has emerged as an effective pharmacological option for obesity management, owing to its substantial effects on weight loss, cardiometabolic risk factors, and patient-reported outcomes. This systematic review and meta-analysis evaluated the efficacy and safety of subcutaneous semaglutide for weight management in adults with overweight or obesity without diabetes. Methods: Randomized controlled trials comparing subcutaneous semaglutide with placebo in adults with overweight or obesity without diabetes were identified through systematic searches of PubMed, the Cochrane Library, and ClinicalTrials.gov. Outcomes included changes in body weight, waist circumference, C-reactive protein (CRP) and serious adverse events (SAEs). A quality assessment and meta-analysis were performed using REVMAN 10.1.1 software. Results: Across nine trials including 6 239 participants, subcutaneous semaglutide significantly reduced percentage body weight from baseline (mean difference [MD] −12.04%, 95% CI −13.08 to −11.00), waist circumference (MD −9.36 cm, 95% CI −10.27 to −8.45), and CRP (MD −40.90%, 95% CI −46.37 to −35.42) versus placebo (all p < 0.00001). The risk of SAEs did not differ significantly between semaglutide and placebo (risk ratio [RR] 1.12, 95% CI 0.76 to 1.65; p = 0.55). Conclusions: Subcutaneous semaglutide is effective for weight management in adults with overweight or obesity without diabetes. The recently published STEP UP trial evaluating semaglutide 7.2 mg provides additional evidence on higher-dose regimens and showed greater weight reduction compared with previously available data, representing a meaningful new contribution to the literature. Longer-term studies are needed to better define the long-term efficacy and safety profile of semaglutide across clinical populations.