Benefits of Adding Glucagon-Like Peptide 1 Receptor Agonists to Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetic Patients With Atherosclerotic Disease and Heart Failure

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce the risk of cardiovascular events and heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF), diabetes mellitus type 2 (DM2), and atherosclerotic cardiovascular disease (ASCVD). The role of glucagon-like peptide 1 agonists (GLP1a) in these patients is unclear. We designed this study to assess if the addition of GLP1a to SGLT2i therapy improves outcomes in patients with HFrEF, DM2, and ASCVD. This was a retrospective cohort study of patients with DM2, ASCVD, and HFrEF in the national Veterans Affairs database. Patients on SGLT2i were propensity matched to patients on both SGTL2i and GLP1a. The co-primary outcomes were HFH and the composite of all-cause death, myocardial infarction, and stroke. We assessed them through a Cox regression model including unbalanced baseline characteristics. From a cohort of 5,576 patients, 343 were propensity matched to each study arm. The addition of GLP1a was associated with a 67% reduction in the 1-year risk of a composite event compared with therapy with SGLT2i (confidence interval 0.138 to 0.714, p = 0.007). The risk of HFH was not significantly different between both arms (p = 0.199). Sensitivity analyses in the unmatched dataset confirmed these findings. In conclusion, the addition of GLP1a to SGLT2i may reduce the risk of adverse events in patients with HFrEF who have DM2 and ASCVD, but it does not affect the risk of HFH.