Tirzepatide linked to lower one-year cardiovascular event rate than sitagliptin in real-world analysis

A population-based cohort study published in The BMJ found that adults with type 2 diabetes and established cardiovascular disease who started tirzepatide had fewer major cardiovascular events over one year than similar adults who started sitagliptin: 2.9% versus 4.4% ^[1][2]. Tirzepatide is the molecule in Mounjaro and Zepbound. Sitagliptin is a diabetes pill that is considered neutral for cardiovascular outcomes ^[2].

What the study measured

The analysis used US administrative claims data collected from May 2022 to May 2025 and was designed to emulate SURPASS-CVOT, a randomized trial of tirzepatide's cardiovascular effects ^[1]. It included 52,971 adults aged 40 or older with type 2 diabetes, a body mass index of at least 25 kg/m2, and established atherosclerotic cardiovascular disease, including prior ischemic stroke, heart attack, or peripheral, coronary, or carotid artery disease ^[1][2]. Of those, 35,353 started tirzepatide and 17,618 started sitagliptin ^[2].

After statistical adjustment, the estimated one-year risk of the main composite outcome, which combined heart attack, ischemic stroke, and death from any cause, was 2.9% with tirzepatide and 4.4% with sitagliptin, an absolute difference of about 1.4 percentage points. The hazard ratio was 0.68 ^[1][2].

The association was concentrated in heart attacks and death. Component hazard ratios were 0.67 for myocardial infarction and 0.55 for all-cause mortality. Stroke did not differ meaningfully between groups, with a hazard ratio of 0.91 ^[1]. The composite counted all deaths rather than cardiovascular deaths specifically ^[2].

Fewer serious infections

Tirzepatide was also associated with lower rates of serious infection. The adjusted hazard ratio was 0.64 for infections requiring hospital admission and 0.40 for infection-related mortality ^[2]. Gastrointestinal adverse events did not differ between the two groups, and negative control outcomes were not associated with treatment ^[1].

The infection findings were secondary results drawn from claims data, not from a trial designed to test whether the drug prevents infection, and residual confounding could explain some or all of the association. No indication for preventing infections has been established ^[2].

Why it matters for patients

The results come with limits that shape how much weight they can carry. The study is observational, so it reports associations rather than causal effects, and the authors said the mortality findings may be particularly susceptible to residual confounding, including differences between the kinds of patients prescribed sitagliptin and tirzepatide ^[1].

Median on-treatment follow-up was less than six months even though the analysis looked at a one-year horizon ^[1]. Claims-based analyses can also be affected by misclassification of treatments or outcomes, and the comparator differs from tirzepatide in how it is taken: sitagliptin is oral, while tirzepatide is injected ^[1]. The authors described generalizability as limited beyond insured US patients with established cardiovascular disease ^[1].

This study compared tirzepatide with sitagliptin, not with semaglutide (sold as Ozempic, Wegovy, and Rybelsus) or with a placebo, so it does not show how tirzepatide compares with those options ^[1][2]. Nothing in the analysis supports using tirzepatide for the purpose of preventing infection ^[2].

Randomized evidence remains the more reliable basis for treatment decisions. SURPASS-CVOT found tirzepatide noninferior, but not superior, to the GLP-1 receptor agonist dulaglutide for major cardiovascular events in people with type 2 diabetes and established cardiovascular disease ^[2].

What happens next

Confirming the infection association would require prospective studies with infection outcomes defined in advance ^[2]. How the cardiovascular and infection patterns would look in groups outside insured US adults with established cardiovascular disease has not been reported ^[1].