Dulaglutide in 2026: still relevant?

Tirzepatide and semaglutide dominate prescriber conversations about GLP-1 receptor agonists, but a narrative review published in Diabetology International in June 2026 makes the case that dulaglutide (marketed as Trulicity by Eli Lilly) still fills gaps the newer agents do not^[1]. The authors, led by Shambo Samrat Samajdar and including Anoop Misra, argue that dulaglutide offers a pragmatic balance of cardiovascular evidence, tolerability, and cost that supports equitable cardiometabolic care worldwide.

What the review covers

The paper surveys dulaglutide's clinical trial programme, real-world persistence data, and head-to-head positioning against semaglutide and tirzepatide. Its central claim is that while tirzepatide and semaglutide produce larger HbA1c and body-weight reductions, dulaglutide offers proven cardiovascular safety, favourable tolerability, and high persistence in real-world analyses^[1]. Rather than treating dulaglutide as an obsolete predecessor, the review frames it as a complementary tool whose strengths differ from, rather than compete with, the newer molecules.

The review also situates dulaglutide within the broader class of GLP-1 receptor agonists, noting that while the class has expanded to include dual and triple receptor agonists, the original single-receptor agents retain distinct evidence bases. Dulaglutide's evidence base spans nine AWARD-series head-to-head trials against other diabetes therapies, plus the pivotal cardiovascular outcome trial discussed below^[1].

The REWIND cardiovascular argument

The review leans heavily on the REWIND trial, a double-blind, placebo-controlled study of 9,901 people with type 2 diabetes across 371 sites in 24 countries, followed for a median of 5.4 years. REWIND tested dulaglutide 1.5 mg weekly against placebo and reported a hazard ratio for major adverse cardiovascular events (MACE) of 0.88 (95% CI 0.79 to 0.99, p = 0.026), translating to roughly a 12% relative risk reduction^[2]. The three-component MACE endpoint comprised non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death.

What distinguishes REWIND from other GLP-1 RA cardiovascular outcome trials is the enrolled population. Around 69% of participants had cardiovascular risk factors only, without established cardiovascular disease, making it the only GLP-1 RA outcome trial to demonstrate a statistically significant MACE reduction in a primary-prevention-heavy cohort^[1][2]. The mean baseline HbA1c was 7.2%, lower than in most comparable trials, suggesting the cardiovascular benefit was not driven solely by glucose lowering. The median follow-up of 5.4 years is also longer than the follow-up periods in LEADER (semaglutide's predecessor liraglutide) and SUSTAIN-6 (semaglutide).

How tirzepatide compares in cardiovascular data

The recently completed SURPASS-CVOT trial randomised 13,165 participants to tirzepatide (up to 15 mg) or dulaglutide 1.5 mg and followed them for a median of roughly 47 months. A post-hoc analysis published in JAMA Cardiology in March 2026 reported a hazard ratio of 0.84 (95% CI 0.79 to 0.90) for a six-component cardiorenal composite endpoint favouring tirzepatide^[3]. The primary endpoint events occurred in 23.7% of the tirzepatide group versus 27.4% of the dulaglutide group. When restricted to a four-component MACE endpoint, the hazard ratio was 0.86, still favouring tirzepatide.

That result positions tirzepatide as the more effective agent in this specific composite, but the review authors note that dulaglutide served as an active comparator rather than placebo^[1]. Both arms received a drug with established cardiovascular benefit, which means the absolute difference between the two is narrower than it would be in a placebo-controlled design. Gastrointestinal adverse events were more common with tirzepatide in SURPASS-CVOT (42.5% versus 35.9%)^[3].

Tolerability and gastrointestinal safety

A separate propensity-score-matched cohort study published in Annals of Internal Medicine compared serious GI safety across all three agents in adults with type 2 diabetes. The composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation showed no statistically significant differences between any pair: semaglutide versus dulaglutide HR 0.96 (95% CI 0.87 to 1.06, roughly 65,238 matched pairs), tirzepatide versus dulaglutide HR 0.96 (95% CI 0.77 to 1.20, roughly 20,893 matched pairs)^[4].

The review uses this finding to argue that the GI tolerability gap between the three drugs is smaller than popular perception suggests. Common side effects like nausea and vomiting affect all GLP-1 RAs in a dose-dependent manner, and the Annals data indicate that the rates of the more serious GI outcomes do not meaningfully differ across the class^[4].

The accessibility case

The review's strongest differentiator for dulaglutide is access. Dulaglutide's once-weekly fixed-dose pen requires no titration, simplifying use for both prescribers and patients. The drug is available across diverse healthcare systems, including low- and middle-income countries where semaglutide and tirzepatide remain limited by cost, supply constraints, or regulatory delays^[1]. In countries where formulary coverage decisions hinge on cost-per-QALY thresholds, a lower-priced agent with proven cardiovascular benefit may be the only GLP-1 RA option that clears the bar.

The authors describe dulaglutide as filling a role for patients and health systems that cannot access or afford the newer agents. This framing does not position dulaglutide as equivalent in efficacy to tirzepatide or semaglutide for glycaemic control or weight loss. Instead, it positions the drug as the available option for populations that would otherwise receive no GLP-1 RA at all^[1].

What the review does not resolve

The paper is a narrative review, not a systematic review or meta-analysis, so it selects rather than exhaustively synthesises evidence. It does not present new data. The comparison with tirzepatide leans on SURPASS-CVOT, which was designed as a non-inferiority trial for tirzepatide rather than a head-to-head efficacy contest^[3]. The cost-accessibility argument, while plausible, is not backed by formal pharmacoeconomic modelling in this paper. And real-world persistence data, cited as a strength of dulaglutide, can reflect prescribing inertia as much as patient preference.

This article is for informational purposes only and does not constitute medical advice. Talk to a healthcare provider before making any treatment decisions.