Efficacy and Safety of Semaglutide in Adults without Diabetes who are Overweight or Obese

INTRODUCTION: Obesity is associated with an increased risk of cardiovascular and metabolic disorders and contributes to the leading cause of death in the US — heart disease. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have recently emerged as a treatment option for obesity. The purpose of this clinical review is to evaluate the efficacy and safety of semaglutide in adults without diabetes who are overweight or obese. METHODS: PubMed was searched using a precise search strategy and the key terms “semaglutide,” “weight loss,” and “without diabetes.” Results were filtered and narrowed using specific inclusion and exclusion criteria. Four high-quality studies were selected for review. This included two RCTs and two systematic reviews and meta-analyses. RESULTS: The two RCTs compared semaglutide to placebo and studied a combined total of 17,908 participants. The two systematic reviews and meta-analyses studied a total of 12 RCTs and over 8,000 participants. These studies evaluated the efficacy and safety of semaglutide by measuring outcomes such as percent weight loss, BMI, waist circumference, blood pressure, HbA1c, and adverse events. DISCUSSION: The data was equivocal across all studies. Semaglutide led to increased weight loss compared to the placebo. There were increased adverse events with semaglutide. The most common were gastrointestinal effects with most being mild to moderate. There was some concern for potential bias in three of the four studies due to affiliation with pharmaceutical companies. Overall, the results suggest semaglutide is a safe and effective treatment for obesity in adults without diabetes who are overweight or obese but further studies are needed to address long-term efficacy, discontinuation, obesity relapse, and accessibility.