Cardiovascular Outcomes with GLP-1 Receptor Agonists Versus SGLT-2 Inhibitors in Patients with Type 2 Diabetes

AIMS: We examined cardiovascular outcomes associated with initiation of GLP-1RA versus SGLT-2i treatment in a real-world setting among patients with type 2 diabetes.

METHODS AND RESULTS: This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8,913 new users of GLP-1RA and 5,275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was for the composite cardiovascular outcome, 5.6% (95% confidence interval (CI): 5.2-6.1) versus 5.6% (95% CI: 4.8-6.3); cardiovascular mortality, 1.6% (95% CI: 1.3-1.9) versus 1.5% (95% CI: 1.1-1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5-2.0) versus 1.8% (95% CI: 1.2-2.5); myocardial infarction, 2.1% (95% CI: 1.8-2.4) versus 2.1% (95% CI: 1.5-2.6); and stroke, 2.5% (95% CI: 2.2-2.9) versus 2.6% (95% CI: 2.2-3.1).

CONCLUSION: In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA versus SGLT-2i was not found to be associated with significant differences in cardiovascular risk.