PURPOSE: Aortic aneurysm rupture and dissection carry mortality exceeding 50%, yet evidence-based medical therapies for this high-risk population remain limited. Despite mechanistic evidence suggesting glucagon-like peptide-1 receptor agonists (GLP-1RAs) stabilize vascular inflammation, no large-scale study has evaluated their impact on acute aortic events in diabetic patients with pre-existing aortic aneurysm.
METHODS: This retrospective active-comparator new-user cohort study utilized TriNetX data from 152 US healthcare organizations (2016-2023). A total of 11,581 adults with type 2 diabetes and documented non-ruptured aortic aneurysm initiating GLP-1RA (n=5676) or dipeptidyl peptidase-4 inhibitors (DPP-4i; n=5905) were identified. DPP-4i was selected as the active comparator given its documented cardiovascular neutrality, whereas sodium-glucose cotransporter-2 inhibitors were not used as a comparator due to their established cardiovascular benefits. After 1:1 propensity-score matching, 3857 patients per group were analyzed using Cox proportional hazards models.
RESULTS: GLP-1RA therapy was associated with lower risks of aortic rupture/dissection requiring surgical repair (hazard ratio [HR] 0.75, 95% CI 0.60-0.94;=0.013), hypertensive crisis (HR 0.77, 95% CI 0.61-0.96;=0.022), and all-cause mortality (HR 0.64, 95% CI 0.57-0.72;<0.001). Numbers needed to treat were 60, 81, and 14 over 5 years, respectively. P P P
CONCLUSION: In diabetic patients with pre-existing aortic aneurysm, GLP-1RA therapy was associated with lower incidence of aortic rupture/dissection, hypertensive crisis, and mortality compared with DPP-4i, supporting preferential consideration of GLP-1RA in this high-risk population.
