Among patients with chronic kidney disease (CKD), dapagliflozin was found to reduce kidney and cardiovascular events among all patients no matter the status of glycemic control, according to the results of a study published in Diabetes Care.
The Dapagliflozin and Prevention of Adverse outcomes in CKD (DAPA-CKD) study (ClinicalTrials.gov Identifier: NCT03036150) recruited patients (N=4304) with CKD at multiple sites. Patients were randomized in a 1:1 ratio to receive dapagliflozin 10 mg/d or placebo for 2.4 years. The primary endpoint was time to sustained estimated glomerular filtration rate decline of at least 50%, onset of end-stage kidney disease, or mortality due to kidney or cardiovascular causes. Normoglycemia (n=738) was defined as hemoglobin A1C (HbA1C) <5.7%, prediabetes (n=660) was defined as HbA1C 5.7% to <6.5%, and type 2 diabetes (n=2906) was defined as HbA1C ³6.5%.
The trial was terminated early due to overwhelming evidence of efficacy.
At follow-up, HbA1c in the treatment group was lower compared with the placebo group, with a difference of -0.1% (95% CI, -0.1% to 0.0%; P =.0018).
The relative risk for the primary composite outcome was decreased (hazard ratio [HR], 0.61; 95% CI, 0.51-0.72), as was the risk for heart failure hospitalization or cardiovascular death (HR, 0.71; 95% CI, 0.55-0.92). A 31% relative risk reduction for all-cause mortality was associated with dapagliflozin therapy.
These findings did not differ significantly on the basis of glycemic control or diabetes status.
Rates of major hypoglycemic events were lower among the treatment cohort (n=14) compared with those receiving placebo (n=28). No significant differences between groups were observed for kidney-related events, amputations, or fractures.
This study may have limited statistical power to evaluate additional endpoints as the trial was terminated early.
The study authors concluded that dapagliflozin successfully prevented CKD progression regardless of diabetes or glycemic control status. Significant differences in safety were not observed, and among patients with type 2 diabetes, major hypoglycemic events were decreased in patients receiving dapagliflozin compared with those receiving placebo.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Persson F, Rossing P, Vart P, et al. Efficacy and safety of dapagliflozin by baseline glycemic status: a prespecified analysis from the DAPA-CKD trial. Diabetes Care. Published online June 28, 2021. doi:10.2337/dc21-0300