Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors vs. Dipeptidyl Peptidase-4 Inhibitors in Frail People With Diabetes Who Were Recently Hospitalized

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) reduce heart failure (HF) hospitalizations and major adverse cardiovascular events (MACE) in general type 2 diabetes populations. The objective of this study was to determine whether SGLT-2Is vs. dipeptidyl peptidase-4 inhibitors (DPP-4Is) are associated with reductions in MACE, HF hospitalizations and mortality in frail people with type 2 diabetes. Methods: We conducted a cohort study of all patients aged ≥30 years with type 2 diabetes discharged from a hospital in Victoria, Australia between January 2014 and March 2018 who received SGLT-2Is or DPP-4Is within 60 days of discharge. Follow-up commenced 60 days after initial discharge, and MACE, HF hospitalization and mortality were recorded. Cox proportional hazards regression with competing risks and stabilized inverse probability of treatment weights (IPTWs), was used to generate subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs). Analyses were stratified into frailty quartiles according to Hospital Frailty Risk Scores (HFRS). Results: Of the 32,043 patients, (41.9% female and 5.9% ≥80 years) in the cohort, 5,152 (16.1%) received SGLT-2Is. Overall, SGLT-2I versus DPP-4I recipients had lower rates of MACE (sHR 0.51; 95% CI 0.46–0.56), HF hospitalization (sHR 0.42; 95% CI 0.36–0.49) and mortality (HR 0.38; 95% CI 0.33–0.43). People with HFRSs in the fourth quartile who received SGLT-2Is versus DPP-4Is also had reduced rates of MACE (sHR 0.37; 95% CI 0.29–0.46), HF hospitalization (sHR 0.43; 95% CI 0.33–0.56) and mortality (HR 0.32; 95% CI 0.25–0.41). Conclusion: SGLT-2Is may be preferred to DPP-4Is for preventing MACE, HF hospitalizations and mortality in frail people with type 2 diabetes.