Tirzepatide Outperforms Dulaglutide in Slashing Major Heart and Kidney Risks, New SURPASS-CVOT Data Reveal

Data presented today at the American College of Cardiology 2026 Scientific Sessions revealed a significant breakthrough in the treatment of high-risk patients with type 2 diabetes. A post hoc analysis of the SURPASS-CVOT trial found that the dual-acting drug tirzepatide (Lilly; Eli Lilly) outperformed the established therapy dulaglutide (Trulicity; Lilly) in reducing a wide range of life-threatening heart and kidney complications.¹

The findings, simultaneously published in JAMA Cardiology, demonstrate that tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist, was associated with a 16% reduction in a broad composite of 6 major adverse events compared to dulaglutide. This composite end point included all-cause mortality, myocardial infarction, stroke, coronary revascularization, hospitalization for heart failure, and serious kidney outcomes.¹

A New Standard in Cardiorenal Care

The SURPASS-CVOT study is notable for being the first large-scale cardiovascular outcome trial to use an active comparator—the GLP-1 agonist dulaglutide—rather than a placebo. Steven E. Nissen, MD, the study’s lead author from the Cleveland Clinic, emphasized that while previous trials showed tirzepatide was noninferior to dulaglutide for a narrower 3-component cardiovascular end point, this new analysis provides a more "comprehensive comparison" of the 2 drugs.²

The trial enrolled 13,165 patients with type 2 diabetes and established cardiovascular disease at 640 centers globally. Participants were randomized to receive either weekly subcutaneous injections of tirzepatide (up to 15 mg) or a fixed 1.5 mg dose of dulaglutide. The mean age of participants was 64 years, and the median follow-up duration was 46.9 months.¹

Breaking Down the Numbers

The results showed that the primary cardiorenal end point occurred in 1559 tirzepatide-treated patients (23.7%) compared to 1803 dulaglutide-treated patients (27.4%). This represents an absolute risk reduction of 3.7%, meaning the number needed to treat to prevent 1 event is just 27 patients.¹

All-cause mortality emerged as a major driver of these results. Death from any cause occurred in 566 patients (8.6%) in the tirzepatide group versus 669 patients (10.2%) in the dulaglutide group, yielding a hazard ratio of 0.84. Other key findings included 527 coronary revascularization events (8%) for tirzepatide vs 617 (9.4%) for dulaglutide, as well as 326 composite kidney end point events (4.9%) for tirzepatide vs 404 (6.1%) for dulaglutide. Similarly, there were 311 myocardial infarction events (4.7%) for tirzepatide vs 357 (5.4%) for dulaglutide.¹

The kidney composite specifically looked at severe outcomes like a persistent doubling of serum creatinine, the need for kidney replacement therapy, or death due to kidney disease. Tirzepatide showed a 21% reduction in these renal events compared to dulaglutide.¹

Safety and Side Effects

Although the cardiorenal benefits were clear, the data also highlighted a higher incidence of side effects in the tirzepatide group. Gastrointestinal adverse events—primarily nausea, vomiting, and diarrhea—were reported by 2827 tirzepatide patients (42.5%) compared to 2387 dulaglutide patients (35.9%).¹

Furthermore, 13.2% of patients on tirzepatide discontinued the drug due to adverse events, compared to 10.1% of those on dulaglutide. However, the researchers noted that serious adverse events were similar between the 2 groups, at approximately 31.8% to 31.9%.¹

Shifting the Treatment Paradigm

Experts at the conference suggested these results could alter how physicians approach the "cardiovascular-kidney-metabolic syndrome." Historically, dulaglutide was a preferred choice because it was proven to reduce major adverse cardiovascular events in the REWIND trial.³ However, tirzepatide’s dual-action mechanism appears to offer added benefits on weight loss, blood pressure, and glycemic control.^1,2

Stephen J. Nicholls, MBBS, PhD, a co-chair of the Academic Executive Committee for the trial, contributed to the interpretation of data that frames this as a "new paradigm" for patient care. By targeting both the GLP-1 and GIP receptors, tirzepatide addresses multiple sources of morbidity and mortality simultaneously.¹

The study did have limitations, notably that it was a post hoc analysis of a trial originally designed for a narrower primary end point. Additionally, the population was limited to high-risk patients, and the researchers cautioned that these results might not apply to lower-risk individuals.¹

Despite these caveats, the SURPASS-CVOT data represent a significant step forward. As Steven E. Nissen, MD, concluded in the presentation, the availability of such highly efficacious therapies marks a turning point in reducing cardiorenal adverse outcomes for millions of patients.¹

REFERENCES

1. Nissen SE. Cardiorenal outcomes: tirzepatide vs dulaglutide in patients with diabetes and cardiovascular disease. Presented at: American College of Cardiology 2026 Scientific Sessions. March 28, 2026; New Orleans, LA.

2. Nissen SE, Wolski K, D’Alessio D, et al. Effects of tirzepatide compared with dulaglutide on expanded cardiorenal outcomes. Presented at: American College of Cardiology 2026 Scientific Sessions. March 28, 2026; New Orleans, LA. https://cattendee.abstractsonline.com/meeting/21230/presentation/18553

3. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial. The Lancet. 2019;394(10193):121-130. doi:10.1016/S0140-6736(19)31149-3