Comparative Effectiveness of GLP-1 Receptor Agonists in Type 2 Diabetes: A Systematic Review

Abstract

Objective:

To systematically evaluate the comparative glycemic efficacy, weight reduction, cardiovascular outcomes, safety, and patient adherence of currently approved GLP-1RAs in the management of T2DM.

Methods:

Comprehensive literature searches of PubMed, Cochrane Library, Embase, and clinical trial databases were conducted up to mid-2025 to identify randomized controlled trials (RCTs), cardiovascular outcome trials (CVOTs), meta-analyses, and observational studies comparing GLP-1RAs. Outcomes extracted included reductions in HbA1c, body weight, occurrence of major adverse cardiovascular events, adverse drug reactions, and treatment adherence rates. Quality assessment used Cochrane and Newcastle-Ottawa tools.

Results:

Twenty-five RCTs and seven CVOTs met inclusion criteria. Semaglutide and tirzepatide consistently demonstrated the greatest HbA1c and weight reductions. Cardiovascular outcomes were notably improved with liraglutide, semaglutide, and dulaglutide. Gastrointestinal side effects were common but transient. Once-weekly and oral formulations showed improved adherence. Data heterogeneity limited head-to-head comparisons.

Conclusions:

GLP-1RAs differ in efficacy and safety profiles. Semaglutide offers superior glycemic and weight benefits, supported by robust cardiovascular evidence. Nevertheless, therapy should be individualized according to patient factors. Future studies should address long-term comparative effectiveness, cost-effectiveness, and personalized treatment strategies.