Background: The rising global prevalence of obesity presents a major public health concern. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) emerge as promising therapeutic agents, showing substantial efficacy in weight reduction in clinical settings. Methods: This review synthesizes data from 1565 clinical trials (Phases I–IV) sourced from the Trialtrove database (November 2024), covering nine GLP-1RAs: mono-agonists (beinaglutide, liraglutide, semaglutide, orforglipron), dual agonists (tirzepatide, mazdutide, survodutide, cagrilintide), and the triple agonist retatrutide. We analyzed trial phase distributions and updated current evidence on safety and efficacy across populations, emphasizing both therapeutic promise and current limitations, particularly the scarcity of long-term and comparative effectiveness data as well as associated adverse effects. Future research must prioritize comparative effectiveness, long-term safety, and personalized strategies for GLP-1RAs, addressing evidence gaps in special populations and treatment individualization. Conclusion: This review synthesizes current evidence on the safety and effectiveness of GLP-1RAs in weight management and potential cardiovascular protection. Further trials are imperative to clarify long-term outcomes, individual variability, and specific adverse effects across diverse populations.
Zhang et al. (2026) studied this question.