Heart failure hospitalization risk associated with use of two classes of oral antidiabetic medications: an observational, real-world analysis

Background: Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium-glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients. Methods: This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included. Depending on their index fill, patients were grouped into either SGLT2 or DPP4 medication class cohorts. The primary outcome was hospitalization for heart failure and the risk was assessed using Cox regression models. Propensity score matching (1: 2 ratio) was used to adjust for potential confounders. Analyses were also stratified by the presence of baseline diabetes complication and age (<65 vs 65+). Results: The matched cohort included 4899 SGLT2 and 9798 DPP4 users. The risk of heart failure hospitalization was lower among SGLT2 users in comparison with matched DPP4 users (2.0% SGLT2 vs 3.1% DPP4; adjusted hazard ratio [aHR] 0.68; 95% confidence interval [CI] 0.54-0.86; p = .001). However, the stratified analyses revealed no risk difference among the majority of the analyzed patients, i.e., those aged <65, which comprised 85% of the matched cohort (aHR = 0.78; 95% CI 0.57-1.05; p = .09), and those without prior complication, which comprised 69% of matched cohort (aHR = 0.83; 95% CI 0.54-1.27; p = 0.40). Conclusions: In this real-life analysis, the rate of hospitalizations for heart failure was significantly lower for patients initiating an SGLT2 compared with a DPP4 medication, specifically among older patients and those with diabetes complication.