Semaglutide Injection for Weight Reduction in Non-Diabetic Adults with Overweight and Obesity

Objective: Obesity is a significant national health concern. Adults with obesity have a decreased life expectancy and a decreased quality of life due to complications from cardiovascular disease, type 2 diabetes, and fatty liver disease. The current treatment options for overweight and obesity include behavior modification, bariatric surgery, and the limited options for pharmacologic therapy. Initiating and maintaining weight loss with diet and exercise is difficult and many adults need pharmacologic assistance in addition to lifestyle interventions. The glucagon-like peptide 1 (GLP-1) receptor agonists are a pharmacological option for obese and overweight adults. The purpose of this study is to investigate whether a commonly used GLP-1 agonist, once-weekly semaglutide, is effective for weight loss in non-diabetic obese or overweight adults in addition to lifestyle intervention and if these results can be extrapolated to patients in clinical practice. Methods: Studies were found in PubMed using search terms “semaglutide” and “obesity”. Several studies were excluded including meta-analyses, non-randomized controlled trials. Studies were also excluded if they included diabetic participants, used oral semaglutide, or compared semaglutide to another drug other than placebo. The final 3 studies (Wilding et al, Study 1; Rubino et al, Study 2; Garvey et al, Study 3) were chosen because they fit this review’s target population and study question. Results: Study 1 showed a -14.9% weight change in adults on semaglutide and lifestyle interventions compared to a -2.4% weight change in adults on placebo and lifestyle interventions with a difference of -12.4% (95% CI: -13.4 to -11.5; p<0.001). 86.4% of the semaglutide group achieved ≥5% weight loss compared to the 31.5% in the placebo group. Study 2 showed that all adults who were on semaglutide for 20 weeks had a weight loss of -10.6%. When adults were randomly assigned to a placebo their weight change after 68 weeks was +6.9% compared to the - 7.9% change on adults who remained on semaglutide after 68 weeks. Study 3 showed that after 104 weeks, adults on semaglutide had a weight change of -15.2% compared to -2.6% in the placebo group. Conclusion: Semaglutide accompanied by lifestyle modifications is an effective tool against overweight and obesity and was significantly more effective than lifestyle interventions with placebo. However, lifelong treatment with semaglutide may be required to maintain the weight reduction and protection from weight-related comorbidities. Although this review showed the significant weight reduction of a two-year treatment with semaglutide, longer studies are needed to better assess the risks and benefits of lifelong treatment with semaglutide. Further studies with better monitoring of adherence to lifestyle interventions are needed to better assess semaglutide’s role as an adjunct to lifestyle interventions.