778-P: SGLT2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors and Risk of All-Cause Hospitalization

Introduction: Clinical trials have shown cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, adoption of SGLT2i in clinical practice has been slow, perhaps in part due to safety concerns. We aimed to assess the association between SGLT2i and risk of all-cause hospitalization as the totality of severe adverse events and benefits, comparing to risks associated with DPP4 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1RA). Methods: We identified patients with type 2 diabetes who initiated SGLT2i (n=2492), DPP4i (n=4762) or GLP1RA (n=1982) between 2015 and 2018 in Geisinger and performed 1:1 propensity score matching on SGLT2i (n=2171) vs. DPP4i (n=2171) and SGLT2i (n=1605) vs. GLP1RA (n=1605). We examined all-cause hospitalization as the main outcome. We also considered two positive controls (major adverse cardiovascular event [MACE] defined as cardiovascular death, myocardial infarction, and stroke; and heart failure [HF] hospitalization), and a negative control (hospitalization due to major bleeding). Results: Mean (SD) age was 58 (13) and 56 (13) years and 46% and 53% were women in the SGLT2i-DPP4i and SGLT2i-GLP1RA matched sample, respectively. During a median follow-up of 14 months, SGLT2i had similar risk of all-cause hospitalization compared with DPP4i (HR [95% CI] 0.85 [0.72-1.01]) or GLP1RA (HR 0.93 [0.77-1.13]). SGLT2i was associated with significantly lower risk of MACE and HF hospitalization compared with DPP4i (MACE: HR 0.70 [0.37, 0.98]; HF: HR 0.61 [0.38, 0.97]) but not with GLP1RA (MACE: HR 1.02 [0.50, 2.08]; HF: HR 0.72 [0.42, 1.23]). Risk of hospitalization due to bleeding was similar between SGLT2i vs. DPP4i or SGLT2i vs. GLP1RA. Conclusions: In this real-world comparison of antidiabetes medications, SGLT2i may be as safe as DPP4i with significant cardiac benefits and have comparable risk-benefit profiles compared with GLP1RA. These results further encourage SGLT2i use in routine diabetes care, particularly among patients at high risk of MACE. Disclosure B. Lyu: None. M. Grams: None. A. R. Chang: Advisory Panel; Self; Reata Pharmaceuticals, Inc., Relypsa Inc., Research Support; Self; Novo Nordisk Inc. L. A. Inker: None. J. Coresh: Consultant; Self; Healthy. io, Research Support; Self; National Institutes of Health, National Kidney Foundation. J. Shin: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK121825)