Study Shows Dapagliflozin Effective Against Chronic Kidney Disease

Hiddo J.L. Heerspink, PhD

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%; 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.