268-OR: The Combined Use of SGLT2 Inhibitors and GLP-1 Receptor Agonists on the Risk of Cardiovascular Events among Patients with Type 2 Diabetes

Background: While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to have cardiovascular benefits when used individually, it remains unknown whether their combined use is associated with further reductions in cardiovascular events in the real-world setting. Objective: To determine whether the SGLT2 inhibitor-GLP-1 RA combination is associated with a decreased risk of major adverse cardiovascular events (MACE) compared with SGLT-2 inhibitors alone. Methods: Using the United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics and Office for National Statistics databases, we identified all patients, >18 years of age, who initiated an SGLT2 inhibitor from 2013 to 2020. Using a prevalent new-user design, we matched 8980 patients initiating an SGLT2 inhibitor-GLP-1 RA combination, in a 1:1 ratio, with patients using SGLT2 inhibitors alone on time-conditional propensity scores. The primary outcome was MACE (myocardial infarction, ischemic stroke, and cardiovascular mortality). Secondary outcomes were the individual components of MACE and heart failure. Patients were followed using an on-treatment approach and Cox proportional hazards regression models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome. Results: Compared with SGLT2 inhibitors alone, the SGLT2 inhibitor-GLP-1 RA combination was associated with a 34% decreased risk of MACE (HR: 0.66, 95% CI: 0.48-0.91). In secondary analyses, the combination was associated with a decreased risk of myocardial infarction (HR: 0.64, 95 CI: 0.42-0.98), while the other outcomes generated more modest effects with CIs including the null. Conclusions: The results of this real-world study suggest that the SGLT2 inhibitor-GLP-1 RA combination is associated with further reductions in the risk of MACE, compared with the SGLT2 inhibitors alone.