Abstract 15741: Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Individuals With Obesity or Overweight but Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated that semaglutide, a GLP-1 receptor agonist, results in clinically important weight loss among individuals with type 2 diabetes. However, its effect on sustained weight loss among those without diabetes is unclear.

Objective: To examine the long-term efficacy and safety of once-weekly semaglutide use for weight loss among individuals with obesity or overweight but without diabetes.

Methods: We systematically searched MEDLINE, Embase, and the Cochrane Libraries to identify RCTs that randomized participants with obesity or overweight but without diabetes to a once-weekly 2.4 mg subcutaneous dose of semaglutide versus placebo. Inclusion was restricted to RCTs that reported change in body weight at a follow-up duration of ≥ 68 weeks. The primary outcome was relative change in body weight from baseline to 68 weeks. Random-effects models with inverse variance weighting estimated weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs).

Results: Three RCTs (n=2,783, 6.0% overweight [BMI 27 to 29.9 kg/m ² ] and 94.0% obese [BMI ≥30 kg/m ² ]) were included. Compared to placebo, once-weekly semaglutide was associated with decreased relative (WMD: -12.0%; 95% CI -13.9%, -10.2%; Table 1) and absolute body weight (WMD: -12.2; 95% CI -13.8, -10.6 kg) at 68 weeks. A total of 86.5% of participants randomized to semaglutide achieved ≥5% weight loss compared to 34.8% with placebo (RR: 2.41; 95% CI 1.26, 4.64). The incidence of gastrointestinal adverse events was higher with semaglutide (RR: 1.45; 95% CI 1.14, 1.84); however, the majority of these events were transient, mild-to-moderate in severity, and did not require treatment discontinuation. A low incidence of serious adverse events was reported (9.5%). CONCLUSIONS: Among individuals with obesity or overweight but without diabetes, semaglutide is efficacious for sustained weight loss.