GLP-1 medicines may cut clot-related risks in chronically inflamed patients

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Jun 10 2026

A large real-world analysis suggests GLP-1 receptor agonists may offer clot-related and survival benefits in a chronically inflamed, high-risk population, while leaving some cardiovascular endpoints unchanged.

Study: Glucagon‐Like Peptide‐1 Receptor Agonists and Cardiovascular Events in Adults With Obesity and Autoimmune Disease: A Target Trial Emulation. Image Credit: Nemes Laszlo / Shutterstock

In a recent study published in the Journal of the American Heart Association, researchers emulated a target trial to assess the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment and the risk of thromboembolic and cardiovascular events in adults with obesity and comorbid autoimmune disease (AID).

Obesity is a leading global public health crisis. Its prevalence has increased from 30.5% in 1999 to 2000 to 41.9% in 2017 to March 2020. Patients with obesity are recognized to have a higher risk of thromboembolic and cardiovascular events. The risk of complications may be compounded in those with comorbid AID. AIDs affect about 15 million people in the United States (US). Studies have shown that individuals with AIDs have 40% to 100% increased risk of thromboembolic and cardiovascular complications.

GLP-1RA therapy is highly effective for glycemic control, weight loss, and cardiometabolic risk reduction. Studies indicate that GLP-1RAs decrease major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) as well as in obese/overweight patients with cardiovascular disease. It is suspected that these benefits apply to other patient populations, although there are insufficient data to support such speculations, particularly in obese patients with AID.

About the Study

In the present study, researchers investigated associations between GLP-1RA use and major cardiovascular and thromboembolic events in adults with obesity and AID. This target trial emulation used electronic health record (EHR) data from the OneFlorida+ network. The study included patients eligible for anti-obesity medication therapy who had an AID diagnosis at cohort entry between January 2014 and January 2024. GLP-1RA treatment initiation was the exposure of interest.

The comparator group included patients who did not initiate GLP-1RAs during the study period. Primary outcomes were myocardial infarction (MI), pulmonary embolism (PE), coronary revascularization, transient ischemic attack (TIA) or stroke, and venous thromboembolism (VTE). Secondary outcomes included emergency department (ED) visits, hospitalizations, and all-cause mortality.

GLP-1RA users and non-users were matched using propensity scores. Incidence rates (IRs) of outcomes per 1,000 person-years were estimated. Cumulative incidence was estimated using the Kaplan-Meier survival method. Cox proportional hazards models estimated hazard ratios comparing GLP-1RA users to non-users. Subgroup analyses were performed for several pre-specified factors, including age, sex, race/ethnicity, and T2D, among others.

Findings

The study included 484,467 individuals with AID who were eligible for anti-obesity medication therapy. Of these, 18,044 were GLP-1RA users, and the remainder were non-users. After propensity score matching, the analytic cohort comprised 26,408 matched patients: 13,204 users and 13,204 non-users. Participants were aged 54.7 years, on average. Most individuals were female (~74%) and non-Hispanic White (~53%). Medications and comorbidities were generally balanced between the two groups.

The IR of MI per 1,000 person-years was 11.2 and 13.1 in GLP-1RA users and non-users, respectively. For TIA or stroke, the IR was 18.8 in GLP-1RA users and 21.9 in non-users. The IR of PE was 6.4 in GLP-1RA users and 9.5 in non-users, and the IR of VTE was 16.6 in users and 20.4 in non-users. Both groups had similar IRs of coronary revascularization. For hospitalization and ED visits, the IRs were 210.4 and 150.9 in GLP-1RA users, compared with 231.3 and 193 in non-users, respectively.

The IR of all-cause mortality was 9.5 in GLP-1RA users and 16.9 in non-users. The team found a lower risk of PE, stroke or TIA, and VTE associated with GLP-1RA use relative to non-use. GLP-1RA use was also associated with a lower risk of mortality and ED visits, while hospitalization was not significantly reduced. Further, GLP-1RA therapy was associated with reduced risks of stroke or TIA, MI, VTE, PE, all-cause mortality, hospitalization, and ED visits in participants with T2D. The associations with PE and VTE were attenuated and not statistically significant in those without T2D.

Conclusions

Together, GLP-1RA treatment was associated with significantly lower hazards of PE, VTE, stroke/TIA, ED visits, and all-cause mortality in adults with obesity and AID. Specifically, GLP-1RA users showed 31%, 17%, 21%, and 44% lower risks of PE, VTE, ED visits, and mortality, respectively, compared with non-users.

In addition, there was a modest statistically significant association for stroke/TIA and a suggestive, non-significant trend for MI, while coronary revascularization and hospitalization were not significantly reduced. 

Overall, the findings suggest potential benefits of GLP-1RA treatment in this high-risk population, although residual confounding and heterogeneity across autoimmune diseases mean the results should not be interpreted as proof of causality.

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