Dulaglutide maintains distinct role in cardiometabolic care despite newer GLP-1/GIP agonists

The landscape of Type 2 Diabetes (T2D) management has evolved significantly with advanced incretin-based therapies. While newer agents like semaglutide and tirzepatide demonstrate superior efficacy in glycemic control and weight loss, dulaglutide retains a crucial position due to its robust cardiovascular (CV) evidence base. Current standard-of-care often prioritizes the most potent agents, potentially overlooking the pragmatic balance of efficacy, safety, and accessibility that dulaglutide offers, especially in diverse global healthcare settings. This review addresses the gap in understanding dulaglutide's contemporary relevance.

This narrative review collated and synthesized existing evidence from major clinical trials, including the landmark REWIND trial and SURPASS-CVOT, to re-evaluate dulaglutide's position in contemporary cardiometabolic care. Researchers analyzed comparative efficacy and safety data against newer incretin-based therapies like semaglutide and tirzepatide. The review focused on key outcomes such as HbA1c reduction, body weight changes, major adverse cardiovascular events (MACE), tolerability profiles, and real-world treatment persistence. The aim was to highlight dulaglutide's complementary role and pragmatic advantages.

The review highlighted the REWIND trial as the only GLP-1R agonist study to show a statistically significant reduction in major adverse cardiovascular events (MACE) in a predominantly primary prevention population, with durable benefits sustained over more than five years of follow-up. Comparative analyses indicated that while tirzepatide and semaglutide achieve superior reductions in HbA1c and body weight, dulaglutide offers proven cardiovascular safety and favorable tolerability.

The SURPASS-CVOT trial established tirzepatide's non-inferiority to dulaglutide for cardiovascular outcomes, thereby reaffirming dulaglutide as a robust comparator with established outcome data. Real-world analyses further demonstrated dulaglutide's high persistence and the practical advantage of its once-weekly, fixed-dose regimen, which requires no titration and enhances accessibility, particularly in resource-constrained settings, including low- and middle-income countries.