Study Shows Dapagliflozin Effective Against Chronic Kidney Disease

October 9, 2020
Kenny Walter

Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.

The investigators also found the effects of dapagliflozin were similar in patients with type 2 diabetes and those without type 2 diabetes.

Patients with chronic kidney disease often have a higher risk of adverse 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 200-5000 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 overwhelming 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.

The researchers did confirm the known safety profile of dapagliflozin.

“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 landmark DAPA-HF trial, investigators found dapagliflozin could reduce the incidence rate of diabetes significantly in non-diabetic patients.

Using the 55% of DAPA-HF participants without type 2 diabetes at baseline, results of the analysis, which was presented at the American Diabetes Association’s (ADA) 80th Scientific Sessions, indicates dapagliflozin reduced new-onset diabetes by 32%, with 4.9% of dapagliflozin patients (64 of 1,298) developing T2D, compared to 7.1% (93 of 1307) in the placebo group.

Of the 2605 non-type 2 diabetes patients 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%; <.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; <.001) at baseline.

The study, “Dapagliflozin in Patients with Chronic Kidney Disease,” was published online in The New England Journal of Medicine.