GLP-1 Analogues in Obesity Therapy: Current Evidence and Future Directions – A Systematic Review

Introduction: Obesity remains one of the most significant global health problems, contributing to increased morbidity, premature mortality, and escalating healthcare expenditures. While lifestyle modification continues to serve as the foundation of therapy, its long-term effects are often modest and difficult to sustain. Bariatric surgery, though highly effective, is invasive and cannot be applied to all patients. For this reason, there is a pressing need for safe and effective pharmacological options. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as highly promising agents for the treatment of obesity. Materials and Methods: A targeted literature search was conducted in PubMed/MEDLINE and PubMed Central covering studies published from 2012 through 2024. Search terms included”GLP-1 receptor agonists, ”“liraglutide, ”“semaglutide, ”“tirzepatide, ” and”obesity.” Eligible studies were randomized controlled trials (RCTs), systematic reviews, and meta-analyses reporting outcomes related to weight reduction and metabolic parameters. Ten key publications were selected for detailed analysis, encompassing pivotal trials of liraglutide, semaglutide, and tirzepatide. Results: Treatment with liraglutide 3.0 mg daily resulted in average weight reductions of 7–8% over treatment periods ranging from 56 to 104 weeks. Semaglutide 2.4 mg once weekly achieved losses of 14–17% in both adult and adolescent populations. Tirzepatide, a dual GLP-1/GIP receptor agonist, demonstrated unprecedented efficacy, with reductions of up to 20.9% at higher doses. Across all agents, improvements were observed in glycemic control, blood pressure, and lipid metabolism. The most frequently reported adverse events were gastrointestinal, including nausea, vomiting, and diarrhea, typically mild, transient, and dose-dependent. Conclusions: GLP-1RAs represent a paradigm shift in obesity pharmacotherapy, providing substantial and clinically relevant weight loss together with broader cardiometabolic benefits. Nonetheless, weight regain following treatment discontinuation, high financial costs, and the need for long-term safety data remain important challenges. Future research should focus on sustaining treatment effects, evaluating newer incretin-based agents, and improving accessibility in order to maximize their global clinical impact.