Effectiveness of low-dose SGLT2 inhibitors in diabetic patients with heart failure: a nationwide cohort study.

Background and objectives: SGLT2 inhibitors (SGLT2i) are a cornerstone of guideline-directed therapy for heart failure (HF). However, the optimal dose for HF remains unclear, as no phase II trials have evaluated dose-response in this population. This study aimed to evaluate whether low-dose (5 mg) of SGLT2i provide comparable efficacy and safety compared with the standard 10 mg dose and to non-users. Methods: This nationwide retrospective cohort study utilized Korean National Health Insurance Service claims data (2013-2018), including 551,760 patients with HF and diabetes, of whom 55,694 were SGLT2i users. After exclusions, propensity-score matching was performed in a 5:5:1 ratio (non-users:10 mg:5 mg). The composite primary outcome was cardiac death, HF hospitalization, or urgent HF-related emergency department (ED) visit. Safety outcomes included ketoacidosis, acute kidney injury (AKI), urinary tract infection, and fractures. Results: In the matched cohort (2,637 on 5 mg; 13,185 on 10 mg; 13,185 non-users), the 5 mg group was associated with lower risk of the primary outcome (HR: 0.73, 95% CI: 0.66-0.81; Conclusions: In patients with diabetes and HF, 5 mg daily SGLT2i was associated with a comparable risk to 10 mg, warranting randomized dose-finding trials.