Comparing cardiovascular benefits between GLP-1 receptor agonists and SGLT2 inhibitors as an add-on to metformin among patients with type 2 diabetes: A retrospective cohort study

This study aimed to compare cardiovascular benefits associated with the use of GLP-1RA versus SGLT2i as add-on therapies to metformin among adults with type 2 diabetes (T2D) with and without a history of cardiovascular complications, using real-world data. Using data from the IBM® MarketScan® Commercial Claims Databases, metformin users above 18years with T2D who initiated GLP-1RA or SGLT2i were identified. The study endpoints include MI, stroke, CHF, and a cardiovascular composite of these three outcomes. Cox proportional hazard regression models were used to compare the risks of cardiovascular endpoints while controlling for demographics and clinical characteristics. We identified 13,006 adults with T2D who initiated a GLP-1RA or SGLT2i as an add-on therapy to metformin and followed for a maximum of 5years. No difference in the endpoints was observed between users of two drugs who did not have established cardiovascular disease at baseline. However, significantly lower CHF risks (HR: 0.47, 95% CI: 0.28–0.79) and cardiovascular composite (HR: 0.67, 95% CI: 0.47–0.97) were observed in SGLT2i users compared with GLP-1RA users, among individuals with established cardiovascular diseases. Results suggest greater cardioprotective benefit from SGLT2i compared to GLP-1RA when used for secondary prevention among adults with T2D. •Enhancing study validity, we emulated protocols from SUSTAIN-8: enrollment criteria and definitions of primary endpoints.•We found consistent evidence that SGLT2i have superior preventive effectiveness on incidence of CHF than GLP-1 RA.•We did not observe differences in endpoints between two drug classes in patients without a history of cardiovascular disease.