Evaluating the Efficacy, Safety, and Practical Considerations of Semaglutide for Weight Loss in Non‐Diabetic Adults: A Narrative Review

ABSTRACT Background and Aims The rising global prevalence of obesity has catalyzed the development of potent glucagon‐like peptide‐1 (GLP‐1) receptor agonists. This narrative review evaluates the efficacy, safety, and practical considerations of injectable semaglutide for weight management, specifically in non‐diabetic adults, a population where weight loss outcomes often differ from those seen in diabetic cohorts. Methods Using information from PubMed, Scopus, and Web of Science, a thematic synthesis was carried out under the guidance of the SANRA procedural framework (2019–2025). The search used tirzepatide as a comparative benchmark and a particular Boolean string to target semaglutide efficacy in non‐diabetic groups. To evaluate metabolic effects and practical obstacles, data from 27 studies including observational studies, randomized controlled trials (RCTs), and qualitative reports, were analytically combined. Results In adults without diabetes, semaglutide (2.4 mg) shows better weight loss efficacy, with mean reductions of roughly 14.9% as opposed to 9.6% in diabetic groups. Significant improvements in cardiometabolic indicators and quality‐of‐life assessments were observed in addition to weight loss. Nevertheless, the main reason for stopping is still gastrointestinal side effects. Long‐term therapeutic utility is greatly impacted by practical obstacles, such as high out‐of‐pocket expenses, worldwide supply limitations, and the possibility of weight gain after cessation. Conclusion Although semaglutide is a novel obesity disease‐modifying medication, its effectiveness depends on how well it is incorporated into multimodal treatment plans. Even though its effectiveness has been shown, equitable public health implementation requires addressing structural issues and safety concerns, such as drug pricing models and insurance coverage. Long‐term durability studies and head‐to‐head trials with next‐generation incretins should be the top priorities for future research.