Efficacy, Safety, and Future of GLP-1 Receptor Agonists: A Systematic Literature Review and Meta-Analysis

Abstract GLP-1 receptor agonists have emerged as important therapeutic agents for type 2 diabetes mellitus (T2DM), but their comparative efficacy and broader applications remain subjects of ongoing research. The aim of the study was to evaluate and compare the efficacy, safety, and clinical applications of three GLP-1 receptor agonists – Semaglutide, Dulaglutide, and Exenatide – through systematic review and meta-analysis. A comprehensive search of PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science (2015–2023) identified 20 randomized controlled trials and observational studies. Primary outcomes included changes in HbA1c and body weight. Risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias tool. Semaglutide demonstrated superior efficacy with mean HbA1c reduction of 1.45% and weight loss of 1.44 kg. Dulaglutide showed consistent reductions in HbA1c (1.1%) and weight (1.2 kg). while Exenatide exhibited moderate effects. Meta-analysis revealed a significant pooled effect estimate favoring GLP-1 receptor agonists. with a mean HbA1c difference of –0.81 (95% CI: –0.92 to –0.70). Gastrointestinal side effects were most common, with Semaglutide showing the highest incidence. This meta-analysis establishes Semaglutide as the most effective GLP-1 receptor agonist for glycemic control and weight reduction, while Dulaglutide and Exenatide offer viable alternatives with fewer side effects. These findings support evidence-based decision-making in T2DM management and highlight the potential broader therapeutic applications of GLP-1 receptor agonists beyond diabetes care.