Real-world analysis links tirzepatide to lower one-year MACE risk in type 2 diabetes

A new observational study published in The BMJ found that adults with type 2 diabetes and established heart disease who started tirzepatide had a lower one-year rate of major cardiovascular events than those who started sitagliptin, a diabetes drug considered neutral for heart risk.^[1][2] The study also found fewer serious infections among tirzepatide users, though researchers cautioned the design cannot rule out other explanations for the differences.^[1][2]

The cohort included 52,971 adults age 40 or older with type 2 diabetes, a body mass index of at least 25, and established atherosclerotic cardiovascular disease, such as prior heart attack, stroke, or artery disease.^[1][2] Researchers compared 35,353 people who started tirzepatide with 17,618 who started sitagliptin, using US insurance claims data collected from May 2022 to May 2025.^[1][2] After statistical adjustment, the one-year risk of the combined outcome — stroke, heart attack, or death from any cause — was 2.9% with tirzepatide compared with 4.4% with sitagliptin, a difference researchers described using a hazard ratio of 0.68.^[1][2]

When the outcome was broken into parts, the pattern was uneven. The hazard ratio was 0.67 for heart attack and 0.55 for all-cause death, but stroke did not differ meaningfully between groups, with a hazard ratio of 0.91.^[1] Researchers also found lower rates of infections requiring hospitalization, with a hazard ratio of 0.64, and fewer infection-related deaths, with a hazard ratio of 0.40, while rates of gastrointestinal side effects did not differ between the two groups.^[1][2]

The study's authors flagged real limits. Because this was not a randomized trial, people who were prescribed tirzepatide may have differed from sitagliptin users in ways the data could not fully capture, including overall frailty, access to care, and how closely they stuck with treatment — a problem researchers call confounding by indication.^[1][2] The authors said the mortality findings in particular may be vulnerable to this kind of bias, and noted that median time actually spent on the assigned treatment was under six months even though outcomes were tracked for a full year.^[1] Claims data can also misclassify diagnoses or treatments, and the study's comparator, sitagliptin, is taken as a pill rather than injected, an additional difference between the two groups.^[1]

Why it matters for patients

This study adds to real-world evidence about tirzepatide (sold as Mounjaro for diabetes and Zepbound for weight management) in people who already have heart disease, but it is not the same kind of evidence as a randomized clinical trial. The gold-standard trial for tirzepatide's heart effects, SURPASS-CVOT, found the drug was noninferior — not superior — to another injectable diabetes drug, dulaglutide, for preventing major cardiovascular events.^[2] That distinction matters: noninferiority means tirzepatide performed at least as well, while the new observational study reports a bigger, superiority-style benefit that has not been confirmed in a randomized setting.^[2]

The infection findings are also preliminary. Researchers said better glucose control, weight loss, and reduced inflammation could plausibly help the body fight infections, but they stressed that tirzepatide should not be viewed as preventing infections based on this study alone, since people who could obtain and stay on a newer injectable medicine may have differed from sitagliptin users in ways researchers could not measure.^[2] Patients already on sitagliptin or another diabetes medicine should not read this study as a reason to switch on their own; treatment choices depend on individual glucose control, weight goals, other health conditions, cost, access, and side effects, which a clinician can weigh with a patient directly.^[2]

What happens next

The study's authors say confirming the infection association would require future studies designed specifically to test infection outcomes, rather than data drawn from insurance claims collected for other purposes.^[2] Broader confirmation of the cardiovascular findings, including whether they hold up outside insured US patients with established heart disease, is not yet available in the sources reviewed for this article.^[1]