Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Dipeptidyl Peptidase-4 Inhibitors, and Risk of Hospitalization

Clinical trials have demonstrated cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). However, their impact on all-cause and cause-specific hospitalization in real-world practice remains unclear. We identified patients with diabetes who initiated SGLT2i (n = 2,492), GLP-1RA (n = 1,982), or dipeptidyl peptidase-4 inhibitors (DPP4i, n = 2,492) between 2015 and 2018 in Geisinger Health System. We examined all-cause hospitalization (net benefit indicator) and cardiovascular disease (CVD) hospitalization (CV benefit indicator), as well as non-CVD hospitalization (harm indicator), using Cox proportional hazards regression. During a median follow-up of 16 months, SGLT2i and GLP-1RA were associated with lower risk of all-cause hospitalization (hazard ratio [HR] 0.85, 95% CI 0.75 to 0.95 for SGLT2i; HR 0.89, 95% CI 0.78 to 0.98 for GLP-1RA), as well as CVD hospitalization (HR 0.61, 95% CI 0.47 to 0.79) for SGLT2i; HR 0.77, 95% CI 0.60 to 0.99 for GLP-1RA) compared with DPP4i. The risks of all-cause and CVD hospitalization were similar between SGLT2i and GLP-1RA. SGLT2i was associated with substantially lower risk of myocardial infarction and heart failure hospitalization compared with DPP4i and lower risk of heart failure hospitalization compared with GLP-1RA. The risk of non-CVD hospitalization did not differ among the treatment groups. These results from real-world comparison further encourage SGLT2i and GLP-1RA use in routine diabetes care, particularly among patients at high risk of cardiovascular events.