In a large real-world study of over 26,000 matched patients, GLP-1 receptor agonists reduced pulmonary embolism by 31%, venous thromboembolism by 17%, and all-cause mortality by 44% among adults with both obesity and autoimmune disease.
44% reduction in all-cause mortalityGLP-1RA users with obesity and autoimmune disease had dramatically lower death rates (HR 0.56, P<0.001) compared to matched non-users
What the researchers found
In the propensity score-matched cohort of 26,408 adults with obesity and autoimmune disease, GLP-1RA use was associated with significantly lower hazards for multiple outcomes compared to non-use:
- Stroke/TIA: HR 0.87 (95% CI: 0.76-0.99; P = 0.039) — 13% reduction
- Pulmonary embolism: HR 0.69 (95% CI: 0.56-0.86; P = 0.001) — 31% reduction
- Venous thromboembolism: HR 0.83 (95% CI: 0.72-0.95; P = 0.007) — 17% reduction
- ED visits: HR 0.79 (95% CI: 0.75-0.83; P < 0.001) — 21% reduction
- All-cause mortality: HR 0.56 (95% CI: 0.47-0.66; P < 0.001) — 44% reduction
Incidence rates per 1,000 person-years were consistently lower for GLP-1RA users across thromboembolic events.
Why it matters
People with autoimmune diseases (like rheumatoid arthritis, lupus, psoriasis, and inflammatory bowel disease) already have heightened cardiovascular risk from chronic inflammation. When combined with obesity — another inflammatory condition — the risk compounds dangerously. This study provides the first large-scale evidence that GLP-1RAs may be particularly beneficial for this dual-risk population. The 44% mortality reduction is especially striking and suggests these peptide drugs may address the underlying inflammatory pathology driving risk in autoimmune patients.
How the study worked
Retrospective cohort study emulating a target trial using 2014-2024 electronic health records from the OneFlorida+ network (21 million individuals across Florida, Georgia, and Alabama). Adults with obesity and autoimmune disease who met anti-obesity medication eligibility criteria were included. Propensity score matching (1:1) with a time-dependent framework was applied to balance baseline characteristics between 13,204 GLP-1RA users and 13,204 non-users. Hazard ratios were calculated for cardiovascular, thromboembolic, healthcare utilization, and mortality outcomes.
What this study cannot tell us
This is an observational study, not a randomized trial, so residual confounding is possible despite propensity score matching. The study used EHR data which may have coding inaccuracies and missing data. Specific autoimmune diseases were grouped together, and benefits may vary by condition. The preprint has not yet undergone peer review. The 44% mortality reduction is very large and should be interpreted cautiously until confirmed in randomized trials. Healthy user bias (GLP-1RA users may be more health-conscious) could inflate benefits.
How to read the evidence
This is a large, well-designed observational study using target trial emulation methodology and propensity score matching — among the strongest non-randomized evidence designs. However, it remains observational and cannot establish causation. It is a preprint that has not yet been peer-reviewed, adding uncertainty to the findings.
When this study was published
Published as a preprint in 2025 using 2014-2024 data, this is very current research addressing a timely clinical question about GLP-1RA benefits in autoimmune disease populations.
The bigger picture
This study extends the cardiovascular benefits of GLP-1RAs to a new, high-risk population — people with autoimmune diseases. The anti-inflammatory properties of GLP-1RAs, combined with their metabolic benefits, may make them uniquely suited for patients whose cardiovascular risk is driven by chronic inflammation. As autoimmune diseases affect 5-8% of the population and obesity rates continue to rise, the intersection of these conditions represents a substantial public health burden that GLP-1 drugs may help address.
Questions still open
- Which specific autoimmune diseases benefit most from GLP-1RA use in terms of cardiovascular protection?
- Is the anti-thrombotic effect of GLP-1RAs a direct pharmacological action or secondary to weight loss and metabolic improvement?
- Should GLP-1RAs be specifically recommended for cardiovascular risk reduction in autoimmune disease patients with obesity?
Common questions
Why are people with autoimmune disease at higher risk for heart attacks and blood clots?
How might GLP-1 drugs help reduce blood clots in autoimmune disease?
Read the original research
GLP-1 Receptor Agonists and Cardiovascular Events in Adults with Obesity and Autoimmune Disease: A Target Trial Emulation.
medRxiv : the preprint server for health sciences
Citation
Dai, Hao; Lee, Yao An; Natalie, Austin; Jackson, Whitney; Pham, Angela; Levine, Jake; Radwan, Rotana; Guo, Jingchuan; Bian, Jiang; Sheer, Amy J. (2025). GLP-1 Receptor Agonists and Cardiovascular Events in Adults with Obesity and Autoimmune Disease: A Target Trial Emulation.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.11.10.25339912