Dulaglutide in the era of tirzepatide and semaglutide: reaffirming its role in contemporary cardiometabolic care.
This narrative review examines the continued clinical relevance of dulaglutide, a once-weekly GLP-1 receptor agonist, in the treatment of type 2 diabetes (T2D) amid growing adoption of newer incretin-based therapies such as semaglutide and tirzepatide. The authors synthesize evidence from major cardiovascular outcome trials, including the REWIND trial—which they highlight as the only GLP-1 receptor agonist trial to demonstrate a statistically significant reduction in major adverse cardiovascular events (MACE) in a predominantly primary prevention population over more than five years—and the SURPASS-CVOT, which established tirzepatide's non-inferiority to dulaglutide for cardiovascular outcomes. The review acknowledges that semaglutide and tirzepatide show superior HbA1c reduction and weight loss compared to dulaglutide, but argues that dulaglutide's fixed-dose, no-titration regimen, established cardiovascular safety profile, real-world tolerability, and lower cost support its continued use—particularly in low- and middle-income countries. Limitations include the narrative (non-systematic) review design, which is susceptible to selection bias, and the lack of head-to-head cardiovascular outcome trials directly comparing dulaglutide to semaglutide or tirzepatide.
Why this grade: This is a narrative review synthesizing existing trial and real-world data rather than generating new primary evidence, and it does not conduct a formal systematic search or meta-analysis.
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.
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