Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP-1) have been found to potentially decrease adverse cardiovascular outcome risk in clinical trials. The objective of this manuscript is to use a federated, real-world data source to compare the cardiovascular benefits between these two medication classes in patients with Type 2 Diabetes (DM2) and established atherosclerotic cardiovascular disease (ASCVD).

Methods: Leveraging a global federated data research platform representing over 57 health care organizations, TriNetX Inc, we retrospectively analyzed two cohorts of DM2 patients with established ASCVD initiating either SGLT2 or GLP-1 medications. The primary outcome was a composite outcome of major adverse cardiovascular events (MACE) including cerebral infarction, acute myocardial infarction, acute coronary event, percutaneous coronary intervention, or coronary artery bypass grafting within 3 years following the initiation of an SGLT2 or GLP1 medication. The secondary outcome was all-cause mortality. Propensity score matching was employed to account for observed baseline confounders. The outcomes were estimated using logistic regression.

Results: The SGLT2 cohort consisted of 48,059 patients while the GLP-1 cohort consisted of 55,090 patients. 40,266 patients remained after propensity score matching (equal cohorts). The matched cohort had an average age of 66 years, were 68% white, and 57% male. The primary composite outcome showed no significant difference between groups [OR: 0.975, (95% CI: 0.942 thru 1.008)]. The GLP1 cohort was found to have higher odds of all-cause mortality compared to the SGLT-2 cohort [OR: 1.121, (95% CI: 1.053 thru 1.193)].

Conclusion: While no significant difference in cardiovascular events was observed, the finding of reduction of all-cause mortality among patient receiving SGLT2i indicates a potential clinical benefit among patients with both DM2 and ASCVD. Next steps should involve different subpopulations to determine which groups are most likely to benefit from selection of SGLT2 over GLP-1 medication classes.