Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

• Published in: The American journal of cardiology 2024-07, Vol.222, p.121-130
• Main Authors: Moiz, Areesha, Levett, Jeremy Y., Filion, Kristian B., Peri, Katya, Reynier, Pauline, Eisenberg, Mark J.
• Format: Article
• Language: English
• Subjects: Blood pressure; Body mass index; Body size; Body weight; Body weight loss; Clinical trials; Diabetes; Diabetes mellitus (non-insulin dependent); Effectiveness; FDA approval; GLP-1 receptor agonist; GLP-1 receptor agonists; Glucagon; Glucagon-like peptide 1; Meta-analysis; Obesity; Overweight; Placebos; Risk assessment; semaglutide; Systematic review; Weight control; Weight loss
• ISSN: 0002-9149; 1879-1913; 1879-1913
• DOI: 10.1016/j.amjcard.2024.04.041

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Random-effects models with inverse variance weighting were used to estimate the weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 randomized controlled trials (n = 3,087) were included. Of the 3 trials that provided body mass index by category (n = 2,783), 94.0% of the participants had a baseline body mass index ≥30 kg/m2. Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD −12.1%, 95% CI −13.5 to −10.7) and absolute body weight (WMD −12.3 kg, 95% CI −13.6 to −11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes.