Associations between antidiabetic drug classes and aortic aneurysm risk in patients with type 2 diabetes: a nationwide cohort study
Y W Lu, C Y Hsu, P H Huang, Y H ShaoAbstract
Background
Aortic aneurysm (AA) is a life-threatening vascular condition whose development is influenced by multiple cardiovascular risk factors, yet epidemiological studies have paradoxically shown a lower incidence and slower progression of AA in patients with type 2 diabetes mellitus (T2DM). Emerging evidence suggests that antidiabetic therapies, rather than hyperglycemia itself, may contribute to this protective association, although comparative large-scale data across different drug classes remain limited.
Purpose
This nationwide cohort study used Taiwan’s National Health Insurance database to investigate the associations between various oral antidiabetic medications and the risk of AA in patients with T2DM.
Methods
This nationwide retrospective cohort study used Taiwan’s National Health Insurance Research Database to identify 3,432,327 adults with type 2 diabetes mellitus between 2006 and 2022, assessing exposure to various antidiabetic medications and incident aortic aneurysm using validated claims-based definitions. Time-to-event analyses were performed with multivariable Cox proportional hazards models incorporating time-varying medication exposure and adjustment for demographic characteristics, comorbidities, and diabetes severity, with subgroup analyses conducted to evaluate the robustness of associations.
Results
Among 3,432,327 patients with type 2 diabetes mellitus (mean age 60 years; 53% male) followed for a mean of 9.2 years, multivariable time-varying Cox analyses showed that metformin (aHR 0.76, 95% CI 0.73–0.79), thiazolidinediones (aHR 0.72, 95% CI 0.66–0.78), sulfonylureas/meglitinide (aHR 0.84, 95% CI 0.81–0.87), α-glucosidase inhibitors (aHR 0.84, 95% CI 0.79–0.90), SGLT2 inhibitors (aHR 0.87, 95% CI 0.78–0.97), and GLP-1 receptor agonists (aHR 0.66, 95% CI 0.47–0.92) were associated with a lower risk of aortic aneurysm. In contrast, insulin use was associated with a higher risk (aHR 1.31, 95% CI 1.24–1.38), while DPP-4 inhibitors were not significantly associated with risk (HR 0.96, 95% CI 0.91–1.01). These associations were consistent across subgroup analyses stratified by age (<65 vs. ≥65 years), sex, cerebrovascular disease, and chronic kidney disease, without substantial heterogeneity.
Conclusions
In this nationwide, population-based, retrospective cohort study, we demonstrated that different classes of antidiabetic agents were heterogeneously associated with the risk of AA. After comprehensive multivariable adjustment with time-varying exposure modeling, the risk of AA was significantly lower among users of metformin, sulfonylureas, TZDs, α-glucosidase inhibitors, SGLT2 inhibitors, and GLP-1RA, whereas DPP-4 inhibitors showed a neutral association.OHA and AA riskFor image description, please refer to the figure legend and surrounding text.Flow chartFor image description, please refer to the figure legend and surrounding text.