Real-World Cohort Study in The BMJ Finds Tirzepatide Cut Major Cardiovascular Events by 32% Versus Sitagliptin

The BMJ published a population-based cohort study on August 5, 2026, examining whether the real-world cardiovascular benefit of tirzepatide in people with type 2 diabetes and established heart disease matches what has been seen in randomized trials of similar drugs. The study, led by Nils Kruger, Sebastian Schneeweiss, and Shirley V. Wang of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital, ran alongside an editorial titled "Tirzepatide and cardiovascular outcomes" by cardiologists Sourbha S. Dani, Arjun Jayakumar, and Sarju Ganatra of the Lahey Clinic in Burlington, Massachusetts.

The researchers used two national US claims databases covering May 2022 to May 2025 and an analytical design the authors describe as previously benchmarked against randomized trial results. They identified 52,971 participants aged 40 or older with type 2 diabetes and established atherosclerotic cardiovascular disease who initiated either tirzepatide (35,353 people) or sitagliptin (17,618 people). Sitagliptin, a DPP-4 inhibitor, was used as an active comparator described in the paper as cardiovascular-outcome neutral, serving as a placebo proxy. Baseline characteristics were balanced between groups using propensity score overlap weighting.

The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, and death from any cause, with follow-up starting the day after treatment initiation and continuing up to one year or until an event, disenrollment, or treatment discontinuation or switching. At one year, the weighted risk of MACE was 2.9% (95% confidence interval 2.5% to 3.4%) in the tirzepatide group versus 4.4% (3.8% to 4.9%) in the sitagliptin group, a risk difference of -1.4 percentage points (95% CI -2.1 to -0.7) and a number needed to treat of 70. That corresponds to a hazard ratio of 0.68 (95% CI 0.58 to 0.80), roughly a 32% relative reduction.

Looking at individual components, tirzepatide was associated with a lower hazard of myocardial infarction (hazard ratio 0.67, 95% CI 0.52 to 0.87; number needed to treat 130), while ischaemic stroke showed no meaningful difference between groups (hazard ratio 0.91, 95% CI 0.64 to 1.28; number needed to treat 2,500). All-cause mortality was lower with tirzepatide (hazard ratio 0.55, 95% CI 0.42 to 0.72). Safety-related outcomes also favored tirzepatide: infections requiring hospital admission were lower (hazard ratio 0.64, 95% CI 0.55 to 0.75) and infection-related mortality was lower (hazard ratio 0.40, 95% CI 0.26 to 0.61). To check for residual confounding, the authors analyzed two negative-control outcomes not biologically expected to be affected by tirzepatide, lumbar radiculopathy and abdominal hernia, and found no association with treatment group for either.

The authors conclude that, using an approach benchmarked against randomized trials, initiating tirzepatide reduced the risk of MACE compared with a placebo-proxy comparator among people with type 2 diabetes and established atherosclerotic cardiovascular disease. They note that reductions in infection-related events point to biological mechanisms beyond the atherosclerotic pathway, and frame the study as an example of how trial-anchored real-world evidence can estimate expected cardiovascular benefit and inform shared decision-making. The underlying research is registered on ClinicalTrials.gov as an observational cohort study (NCT07203677) from the same Brigham and Women's Hospital research program.

The study does not change tirzepatide's regulatory status. The drug is already approved by the FDA (as Mounjaro for type 2 diabetes and Zepbound for chronic weight management), the European Medicines Agency, and Australia's Therapeutic Goods Administration. Because the analysis is observational rather than a randomized controlled trial, it cannot fully rule out residual confounding despite the negative-control checks, and its findings apply specifically to people with type 2 diabetes and pre-existing atherosclerotic cardiovascular disease rather than the broader population using tirzepatide for weight management alone. Nothing in the study constitutes treatment or dosing guidance.