Effectiveness of low-dose SGLT2 inhibitors in diabetic patients with heart failure: a nationwide cohort study
Abstract
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; P < 0.001) and all-cause death (HR 0.85, 95% CI 0.74–0.97; P = 0.019) compared with 10 mg, with similar safety profiles. Significant interactions were observed: the relative effect of 5 mg vs. 10 mg differed by sex and body weight for urgent ED visits, and by BMI for AKI. Sensitivity analyses across multiple time points showed consistent results, with the 5 mg group…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 551,760 participants or records.
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