Efficacy and safety of once-weekly subcutaneous semaglutide in adults with overweight or obesity: systematic review with meta-analysis

Background: To evaluate the efficacy and safety of once-weekly subcutaneous semaglutide treatment in overweight or obese patients without type 2 diabetes. Methods: Randomized clinical trials that accessed the impact of once-weekly semaglutide on body weight and safety outcomes in overweight or obese patients were retrieved from Pubmed, EMBASE, and Lilacs up to November 2023. Risk of bias was assessed with RoB 2.0, and certainty of evidence (CoE) with GRADE. We conducted a random-effects meta-analysis. Results: We included ten publications with 22.155 patients. Semaglutide decreased relative body weight (MD: -11.80; 95%CI: -13.53 to -10.07; CoE: High), absolute body weight (MD: -11.58; 95%CI: -13.25 to -9.90; CoE: High) and BMI (MD: -4.15; 95%CI: -4.85 to -3.45; CoE: High). Semaglutide also increased the proportion of patients who achieved 5%, 10% and 15% of weight loss ([weight loss ≥5%: RR 2.29, 95% CI: 1.88 to 2.80; CoE: High]; [weight loss ≥10%: RR 4.54, 95% CI: 3.45 to 5.98; CoE: High]; [weight loss ≥15%: RR 8.29, 95%CI: 5.54 to 12.39; CoE: High]). Semaglutide leads to small risk to adverse events (RR: 1.03; 95%CI: 1 to 1.06; CoE: High), no difference in the serious adverse events (RR: 1.07; 95%CI: 0.70 – 1.62; CoE: Low), but increases in the risk to discontinued treatment (RR: 2.03; 95%CI: 1.87 – 2.20; CoE: High) and gastrointestinal adverse events (RR: 3.26; 95%CI: 1.99 – 5.34; CoE: Moderate). Conclusion: This up-to-date systematic review highlights that once-weekly semaglutide treatment resulted in clinically important weight loss, becoming a promising adjuvant therapy to treat obesity.