Q&A: Tirzepatide Outperforms Dulaglutide in Cardiorenal Outcomes, With Steven Nissen, MD

New data from a post hoc analysis of the SURPASS-CVOT trial suggest that tirzepatide may offer broader protection against cardiovascular and kidney outcomes than dulaglutide in patients with type 2 diabetes and established cardiovascular disease. The findings, presented at the American College of Cardiology Scientific Sessions 2026, expand on prior results demonstrating noninferiority for major adverse cardiovascular events and instead evaluate a more comprehensive cardiorenal endpoint.

In the analysis, treatment with the dual GLP-1/GIP receptor agonist was associated with a lower incidence of a 6-component composite outcome—including all-cause mortality, myocardial infarction (MI), stroke, coronary revascularization, heart failure hospitalization, and adverse kidney outcomes—compared with dulaglutide (hazard ratio [HR], 0.84; P < .001). The broader endpoint reflects growing recognition that cardiometabolic disease affects multiple organ systems and clinical outcomes beyond traditional 3-point MACE.

To help clinicians interpret the findings and understand their relevance for everyday practice, we spoke with Steven E. Nissen, MD, who presented the analysis at ACC.26.

Making Sense of Expanded Cardiorenal Outcomes, With Steven Nissen, MD

Q: Could you provide a brief overview of your study and its findings?

A: So I presented a analysis of the SURPASS-CVOT trial, which was the first active control study of an incretin based therapy. All the others have been placebo controlled. So this was a study that compared tirzepatide with dulaglutide. And the primary analysis published late last year was a non inferiority analysis based upon a three component endpoint, cardiovascular death, myocardial infarction and stroke. That endpoint was chosen because the comparator, dulaglutide had received an indication via the REWIND trial for reducing the risk of cardiovascular death, stroke and MI and it showed not inferiority, but not superiority.

But we did the adjudication at the Cleveland Clinic for that trial, and we adjudicated more endpoints than those three narrowly defined endpoints, because we know that this disorder, obesity, diabetes, cardiovascular disease affects a lot more than just those three endpoints.

So the analysis that I did and presented was a six component outcome that looked at the totality of the effects of these drugs on cardiovascular and renal health…

And when that analysis was completed, what we saw was not non inferiority, but a lower rate of adverse outcomes with tirzepatide compared with dulaglutide. And it was quite significant. It was a hazard ratio of 0.84, with a P value of less than 001…

So what this tells us is that targeting two incretins… GLP one and GIP is actually a better strategy in terms of reducing major morbidity and mortality than targeting just GLP one alone.

Q: The reduction in all-cause mortality is striking. What is driving this signal?

A: Well, it's… three things. It's cardiovascular death, for sure, we know we see a reduction in infectious mortality… People die of sepsis, they die of COVID…And now we didn't actually measure it in this trial, but we also know from other studies that cancer mortality… seem to be reduced. So there's just a lot of causes of death that are affected in patients with diabetes, obesity and pre existing cardiovascular disease, and they're all benefiting. And when you sum them all up together, you get a pretty robust effect.

Q: Some effects appeared modest. Is the overall benefit driven by 1 or 2 dominant outcomes, or is this effect truly a consistent class effect?

A: This is now the only GLP-1/GIP drug. So we don't, we can't yet talk about class effect. But yes, there were areas that were stronger in terms of what we observed, the all cause of mortality effect, very strong. Coronary revascularization, very, very strong benefits, but really, every one of the components can treat it to some extent. And we should be careful here, because in any study you know the heterogeneity of outcomes, there's going to be some differences from one endpoint to the other. It doesn't necessarily inform us that other drugs or other studies are going to show the same pattern, but it does certainly shows everything was moving in the right direction, and that's really the best we can say about a study like this. By the way, the event rate here was quite high, if you look at those six components around 25% of the patients hadn't had a morbid or mortal outcome. So this disease, diabetes, with, you know, high cardiovascular risk and obesity, it is a very high event rate, even a relatively modest length trial.

Q: Based on these data, do you believe clinicians should preferentially choose tirzepatide over other GLP-1 Ras for patients with ASCVD?

A: It's hard to make that claim. Remember, this is a secondary analysis of a trial you usually want to see before you change practice definitively you know, a pre specified primary analysis that shows a benefit we're going to get that there's a study ongoing. I happen to be the study chair called SURMOUNT MMO, and it is studying compared with placebo tirzepatide, in a group of people, interestingly enough, that have both primary prevention patients and secondary prevention patients without diabetes. So we're going to find out in a much broader population whether or not targeting with a dual incretin therapy, a GLP one and a GIP-targeted therapy, whether it really is superior to placebo. Now it's not an active control trial, like SURPASS-COVT but it's going to give us some more information.

Editors’ Note: Nissen reports disclosures with Amgen, AstraZeneca, Bristol Myers Squibb, Novartis, Medtronic, Eli Lilly, and others.

References

1. Nissen SE, Wolski K, D’Alessio D, et al. Cardiorenal Outcomes With Tirzepatide Compared With Dulaglutide in Patients With Diabetes and Cardiovascular Disease: A Post Hoc Analysis of the SURPASS-CVOT Randomized Clinical Trial. JAMA Cardiol. March 28, 2026. Accessed April 10, 2026. doi:10.1001/jamacardio.2026.0767
2. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with Tirzepatide versus dulaglutide in type 2 diabetes. NEJM. 2025;393(24):2409-2420. doi:10.1056/nejmoa2505928
3. Lam CSP, Rodriguez A, Aminian A, et al. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial. Obesity (Silver Spring). 2025;33:1645-1656. doi:10.1002/oby.24332