News release

From: BMJ Group

GLP-1 drug linked to heart benefits for high-risk patients 

Findings from clinical practice will help inform shared decision making

Adding the GLP-1 receptor agonist drug tirzepatide (marketed as Mounjaro) to standard care for patients with type 2 diabetes and heart disease is associated with a lower risk of a major cardiovascular event, such as a heart attack or stroke, finds a study published by The BMJ today.

Randomised trials and observational studies have shown non-inferior effects of tirzepatide compared to another GLP-1 receptor agonist, dulaglutide, for major adverse cardiovascular events (MACE) - a combined measure of heart attack, stroke, and death from any cause. But evidence on the effects of adding tirzepatide to standard care is more limited, resulting in uncertainty for both regulators and clinicians.

To address this, researchers analysed clinical practice data from two US health insurance claims databases between May 2022 and May 2025. They aimed to estimate the cardiovascular effects of adding tirzepatide to standard care for patients with type 2 diabetes, a body mass index of at least 25, and established heart disease by comparing the outcomes to sitagliptin, another diabetes drug.

Sitagliptin was chosen as a neutral placebo proxy based on several studies showing no effect on cardiovascular outcomes.

The main outcome of interest was a reduction in MACE, which was monitored from the first day of treatment up to one year, or until the individual stopped or switched treatment, or disenrolled from the health plan.

Factors including age, sex, race, body mass index, previous heart problems, other chronic conditions, and medication use were taken into account, and a technique called propensity score overlap weighting was used to balance out differences between the two groups to draw more reliable conclusions.

A total of 52,971 individuals were included in the analysis (average age 70 years; 51% female), of whom 35,353 started tirzepatide and 17,618 started sitagliptin.

At one year, the risk of MACE was 2.9% in the tirzepatide group and 4.4% in the sitagliptin group (a 32% relative reduction), and the researchers estimate that for every 70 patients starting tirzepatide, one case of MACE would be prevented.

For individual MACE components, tirzepatide was associated with a 33% lower risk of heart attack compared with sitagliptin, whereas ischaemic stroke showed no meaningful difference.

Infections requiring hospital admission were also lower with tirzepatide (one admission prevented for every 48 patients), as was infection related death (one death prevented for every 200 patients) and death from any cause (one death prevented for every 122 patients).

This is an observational study, but the researchers previously benchmarked their design, data, and analytics infrastructure against a randomised controlled trial before drawing conclusions about cause and effect.

They also acknowledge several limitations including a relatively short follow-up period, which may underestimate long term cardiovascular and safety effects, possible misclassification of treatment duration or outcomes, and findings may not apply to other healthcare systems or patients without established cardiovascular disease.

However, they conclude: “This study shows how trial-anchored evidence from clinical practice can estimate the expected cardiovascular benefit of initiating tirzepatide beyond standard background treatment and inform shared decision making.”

A linked editorial notes that while this study provides an important, transparent estimate of what initiating tirzepatide might achieve in routine care, it does not establish a mortality indication or define the best sequence for cardiometabolic therapy.

The authors say longer follow-up, randomised and pragmatic comparisons, and more studies of additive benefit on contemporary background treatment are needed. Furthermore, cardiovascular efficacy cannot benefit a population if cost, authorisation barriers, supply, and discontinuation prevent sustained treatment, they add.

As such, they conclude: “The signal is compelling; the causal and clinical placement questions remain open.”