• Adults with type 2 diabetes and established CVD had lower risk for CV events with tirzepatide compared with sitagliptin.
• Tirzepatide decreased risk for infections leading to hospital admission.

Tirzepatide reduced risk for major adverse cardiovascular events among adults with type 2 diabetes and established atherosclerotic cardiovascular disease, according to real-world data published in The BMJ.

As Healio previously reported, the SURPASS-CVOT trial found tirzepatide (Mounjaro, Eli Lilly) conferred a similar reduction in risk for CV events as dulaglutide (Trulicity, Eli Lilly) among adults with type 2 diabetes and atherosclerotic CVD. In a new study using data from two national claims databases in the U.S., researchers compared CV outcomes among adults using tirzepatide with those using the DPP-IV inhibitor sitagliptin (Januvia, Merck).

“The recent CV outcomes trial, SURPASS-CVOT, established that tirzepatide was noninferior to dulaglutide, but it did not directly quantify the CV benefit of adding tirzepatide to contemporary standard care,” Nils Krüger, MD, MPH, physician data scientist at Brigham and Women’s Hospital and Harvard Medical School, told Healio. “This matters because clinicians and patients often want to know not only how tirzepatide compares with another active treatment, but also how much benefit they might expect from initiating it.”

Researchers collected data from the Optum Clinformatics and Merative MarketScan databases of adults aged at least 40 years with type 2 diabetes and established atherosclerotic CVD from May 2022 to May 2025. Propensity score matching was used to compare 7,442 adults receiving tirzepatide with an equal number of people using sitagliptin. Sitagliptin was used as a placebo proxy because it has been shown to have no effect, beneficial or harmful, on CV outcomes, the researchers wrote.

The primary outcome was major adverse CV events, which were a composite of myocardial infarction, stroke and all-cause mortality. An expanding composite outcome consisting of MI, stroke, coronary revascularization and unstable angina was also assessed.

During a mean on-treatment follow-up of 182 days, 1-year risk for a major adverse CV event was 2.9% with tirzepatide and 4.4% with sitagliptin. Adults receiving tirzepatide had reduced risk for major adverse CV events compared with those receiving sitagliptin (HR = 0.68; 95% CI, 0.58-0.8).

Tirzepatide was associated with lower risk for MI (HR = 0.67; 95% CI, 0.52-0.87) and all-cause mortality (HR = 0.55; 95% CI, 0.42-0.72) compared with sitagliptin. There was no difference in ischemic stroke risk.

In analysis of the expanded composite endpoint, tirzepatide was associated with lower risk for major adverse CV events than sitagliptin (HR = 0.92; 95% CI, 0.85-0.99).

“For patients with type 2 diabetes and established CVD, the findings support viewing tirzepatide as more than a glucose- or weight-lowering treatment,” Krüger said. “Its potential CV benefit can be discussed in absolute terms during shared decision-making.”

Adults receiving tirzepatide had lower risk for infection-related mortality than those using sitagliptin (HR = 0.4; 95% CI, 0.26-0.61). Tirzepatide also reduced risk for infections leading to hospital admission (HR = 0.64; 95% CI, 0.55-0.75), infections in any care setting (HR = 0.83; 95% CI, 0.78-0.87) and urinary tract infections (HR = 0.83; 95% CI, 0.76-0.91) compared with sitagliptin.

“This is an intriguing signal that warrants further investigation and points to additional benefits of incretin-based therapies beyond their established metabolic effects,” Krüger said of the reduced infections risk with tirzepatide.

According to Krüger, longer-term studies are needed to better assess CV benefit with tirzepatide.

“Future research should also disentangle atherosclerotic from nonatherosclerotic mechanisms, and determine how much of the reduction in mortality may be related to fewer serious infections,” Krüger said.

Nils Krüger, MD, MPH, is a physician data scientist in the division of pharmacoepidemiology and pharmacoeconomics, department of medicine at Brigham and Women’s Hospital and Harvard Medical School; and resident physician in the department of cardiology at TUM University Hospital German Heart Center at Technical University of Munich in Germany. Krüger can be reached at nkruger1@bwh.harvard.edu or LinkedIn @nilskruger.