Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis

Abstract

Background: The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of subcutaneous semaglutide as treatment for obesity in patients without diabetes.

Methodology: A comprehensive search of PubMed/MEDLINE, Cochrane and Google scholar was performed to identify trials on the efficacy and safety of subcutaneous semaglutide on patients with obesity without diabetes. Primary outcome was expressed as percent mean weight difference. Secondary outcomes including risk for gastrointestinal adverse events, discontinuation of treatment and serious adverse events were expressed as risk ratios. These were calculated using the random effects model.

Results: The study included 4 randomized controlled trials having a total of 3,613 individuals with obesity without diabetes. The mean difference for weight reduction was -11.85%, favoring semaglutide [95% confidence interval (CI) (-12.81,-10.90), p<0.00001]. Secondary outcomes showed that the risk of developing gastrointestinal adverse events was 1.59 times more likely with semaglutide (RR 1.59, 95%CI [1.34, 1.88], p<0.00001). Risk for discontinuation due to adverse events was twice as likely in the semaglutide group (RR 2.19, 95%CI [1.36,3.55], p=0.001) and the risk for serious adverse events was 1.6 times more likely for semaglutide (RR1.60, 95%CI [1.24, 2.07], p=0.0003). Serious events were mostly of gastrointestinal and hepatobiliary disorders such as acute pancreatitis and cholelithiasis.

Conclusion: Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss with an 11.85% reduction from baseline compared to placebo. This supports the use of semaglutide for weight management in obesity. However, risk of gastrointestinal adverse events, discontinuation of treatment and serious adverse events were higher in the semaglutide group versus placebo.

Keywords: Glucagon-like Peptide -1; obesity; semaglutide; weight loss.

Figure 1

Flow diagram for systematic review and study selection of randomized controlled trials on semaglutide for weight loss in patients who are obese without diabetes.

Figure 2

Risk of bias assessment of the included randomized controlled trials.

Figure 3

(A) Forest plot showing the effect of semaglutide on mean weight difference versus placebo. (B) Sensitivity analysis showing the effect of semaglutide on mean weight difference versus placebo.

Figure 4

(A) Forest plot showing the risk of gastrointestinal adverse events with semaglutide treatment versus placebo. (B) Sensitivity analysis showing the risk of gastrointestinal adverse events with semaglutide treatment versus placebo.

Figure 5

(A) Forest plot showing the risk of adverse events leading to discontinuation of treatment with semaglutide versus placebo. (B) Forest plot showing the risk of serious adverse events with semaglutide treatment versus placebo.