Risk factors associated with SGLT2 inhibitor discontinuation in diabetic patients with heart failure

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown benefits in patient with heart failure (HF), however, adherence remains a significant issue: with only 60% of patients continuing usage beyond a year. This study aims to identify patients at risk of discontinuing SGLT2i and promote its judicious use to reduce hospitalizations and improve cardiovascular outcomes. Using the Korean National Health Insurance Service database, patients diagnosed with HF and diabetes mellitus (n = 1,665,565) between 2013 and 2018 were identified. Among them, 55,694 participants prescribed SGLT2i were enrolled. The primary endpoint included 1) all-cause mortality and 2) SGLT2i-related hospitalization, encompassing incidents such as ketoacidosis, acute kidney injury, urinary tract infections, fall-related fractures, and other unplanned hospitalizations. During the follow-up period (median: 2.3 years; range: 1.2-3.6 years), 8,463 participants reached the primary endpoint (25.5 for all-cause death and 39.4 for SGLT2i-related hospitalizations per 1,000 person-years). Independent risk factors for the primary endpoint in multivariate Cox regression and propensity-score matching analyses included age of ≥ 70 years, body mass index (BMI) <18.5 kg/m2, body weight <60 kg, anemia, chronic kidney disease, and the use of diuretics. Age (hazard ratio [HR] 1.45, 95% confidence interval [CI]: 1.36-1.54), BMI (HR 1.78, 95% CI: 1.29-2.45), body weight (HR 1.17, 95% CI: 1.09-1.26) and the use of furosemide (HR 1.45, 95% CI: 1.22-1.74) (all p<0.001) were consistent independent risk factors in the propensity score-matched cohort. Having three or more risk factors was associated with an adjusted HR that was 3.04 times higher than cases with no risk factor (95% CI: 2.83-3.28, p<0.001). Old age, low weight or BMI, and the use of diuretics are risk factors that hinder the continuous use of SGLT2i in diabetic patients with HF. Close monitoring for side effects is essential when prescribing SGLT2i, particularly for those with multiple risk factors.