Sodium-glucose cotransporter 2 inhibitors: A drug with antidiabetic and cardioprotective properties
Journal
Journal of diabetes investigation
Journal Volume
12
Journal Issue
3
Date Issued
2021-03
Author(s)
Abstract
Recently, two large double-blind randomized controlled trials testing the effect of sodium–glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure with and without diabetes have led to a paradigm shift for the indication of this class of drugs. Key clinical features and main results in these two studies are summarized in Tables 1 and 2. The Dapagliflozin And Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial included 4,744 patients with heart failure and a reduced ejection fraction (HFrEF)1. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. Patients who received dapagliflozin showed a 26% lower risk of developing primary outcomes, compared with patients who received a placebo. Importantly, this trial included patients without diabetes, in addition to patients with diabetes. In a prespecified exploratory analysis, the cardioprotective effect was observed in patients with diabetes, prediabetes and normoglycemia2. In the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced), 3,730 patients with HFrEF were recruited3. The primary outcome was a composite of adjudicated cardiovascular death or hospitalization for heart failure. Patients in the empagliflozin group had a 25% reduction in developing primary outcome, compared with patients in the placebo group. Similarly, the beneficial effect was observed in both patients with and without diabetes. In the DAPA-HF study, prespecified extensive analyses in patients with and without diabetes were carried out2. The results for each individual component of primary outcome and each secondary outcome were consistent in patients with and without diabetes. In addition, analysis of patients without type 2 diabetes at baseline and with hemoglobin A1c 60 mL/min/1.73 m2 were excluded. The trial tests the effect of empagliflozin on the first occurrence of a sustained decline in eGFR ≥40%, end-stage kidney disease, cardiovascular death or renal death. The study is estimated to be completed in 2022. Taken together, the results from DAPA-CKD and EMPA-KIDNEY trials will broaden our understanding of the renal protective effects of SGLT2 inhibitors in patients with chronic kidney diseases and without diabetes. In addition, data on patients with eGFR lower than current label will provide more information on the effectiveness and safety in patients with advanced chronic kidney diseases. In conclusion, data from DAPA-HF and EMPEROR-Reduced trials suggest that SGLT2 inhibitor is a drug with both antidiabetic and cardioprotective properties. In the near future, its renal protection effect in patients with chronic kidney diseases will be revealed. With these results, the application of SGLT2 inhibitors is expected to be widespread, which will improve the clinical outcomes of patients with diabetes, heart failure or chronic kidney diseases. The author declares no conflict of interest.
SDGs
Type
journal article