Dulaglutide in the era of tirzepatide and semaglutide: reaffirming its role in contemporary cardiometabolic care

UNLABELLED: The management of type 2 diabetes (T2D) has entered a new era with the advent of advanced incretin-based therapies. Therapeutic agents such as semaglutide and tirzepatide have demonstrated exceptional efficacy in improving glycemic control, inducing substantial weight loss, and reducing cardiometabolic risk, thereby redefining therapeutic expectations. Yet, dulaglutide retains a distinct role supported by its strong cardiovascular evidence base. The REWIND trial remains the only GLP-1 receptor agonist study to show a statistically significant reduction in major adverse cardiovascular events (MACE) in a predominantly primary prevention population, with durable benefit sustained over more than five years of follow-up. Comparative trials highlight that while tirzepatide and semaglutide deliver superior reductions in HbA1c and body weight, dulaglutide offers proven cardiovascular safety, favourable tolerability, and high persistence in real-world analyses. Its once-weekly, fixed-dose regimen requires no titration and is accessible across diverse healthcare systems in low- and middle-income countries, including those constrained by cost or resources. The SURPASS-CVOT established tirzepatide's non-inferiority to dulaglutide for cardiovascular outcomes, reaffirming dulaglutide as an established comparator with robust outcome data. This narrative review collates evidence in this regard and argues that dulaglutide should be viewed not as superseded but as complementary offering a pragmatic balance of efficacy, safety, and accessibility that supports equitable cardiometabolic care worldwide. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-026-00910-9.