Patients withoften have a higher risk of both kidney and outcomes, increasing the need for a treatment that could treat the renal conditions while decreasing the risk of cardiovascular disease.
A team, led by Hiddo J.L. Heerspink, PhD, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, tested the effect of dapagliflozin, a SGLT2 inhibitor, in CKD patients, both with or without type 2 diabetes.
In the study, the investigators randomized 4304 patients with an estimated glomerular filtration rate (eGFR) between 25-75 ml per minute per 1.73 m2 of body surface area and a urinary albumin-to-creatinine ration (with albumin measured in milligrams and creatinine measured in grams) of 200-500 to receive either 10 mg once daily of dapagliflozin or a placebo.
The investigators sought primary outcomes of a composite of a sustained decline in the eGFR of at least 50%, end-stage kidney disease (ESKD), or death from renal or cardiovascular causes.
However, because of poor efficacy, the independent data monitoring committee recommended stopping the trial. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 patients (9.2%) in the study treatment group, in comparison to 312 of the 2152 individuals (14.5%) in the placebo arm (HR, 0.61; 95% CI, 0.51-0.72; P <0.001; number needed to treat to prevent 1 primary outcome event, 19; 95% CI, 15-27).
The hazard ratio for the composite of a sustained decline in the eGFR of at least 50%, ESKD, or death from renal causes was 0.56 (95% CI, 0.45-0.68; P <0.001), while the HR for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55-0.92; P = 0.009).
In addition, death occurred in 101 patients (4.7%) in the dapagliflozin group and 146 individuals (6.8%) in the placebo group (HR, 0.69; 95% CI, 0.53-0.88; P = 0.004).
The investigators also found the effects of dapagliflozin were similar in patients with type 2 diabetes and those without type 2 diabetes.
However, the researchers did confirm the known safety profile of dapagliflozin despite a lack of efficacy in the study.
“Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo,” the authors wrote.
Recently, as part of the landmarktrial, investigators found dapagliflozin could reduce the incidence rate of diabetes significantly in non-diabetic patients.
Using the 55% of DAPA-HF participants without diabetes at baseline, results of the analysis, which was presented at the American Diabetes Association’s (ADA) 80th Scientific Sessions, indicates nondiabetics patients receiving dapagliflozin reduced the rate of new-onset diabetes by 32% compared to patients receiving placebo.
Of the 2605 nondiabetics identified for inclusion, 157 developed type 2 diabetes during the trial, of which 150 were classified as having prediabetes at baseline. Compared to those who did not develop type 2 diabetes, those with incident type 2 diabetes had a higher mean baseline HbA1c (6.2±0.3% vs 5.7±0.4%; P <.001), greater BMI (28.5±5.9 vs 27.1±5.7 kg/m2; P=.003), and lower eGFR (61.5±17.4 vs 68.2±19.3 ml/min/1.73 m2; P <.001) at baseline.
The study, “Dapagliflozin in Patients with Chronic Kidney Disease,” was published online in The New England Journal of Medicine.