A predetermined analysis from the DAPA-CKD trial examines dapagliflozin′s effects on serious adverse renal and cardiovascular events in participants with and without diabetes who had chronic kidney disease.

Kidney failure, estimated in terms of both reduced glomerular filtration rate (GFR) and albuminuria, is associated with increased risk for cardiovascular (CV) outcomes. Patients with both type 2 diabetes and kidney dysfunction, represent a particularly vulnerable patient population. As a solution to the problem, many experts have recommended Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) therapy. Over the past 2 decades, several large clinical trials investigating sodium-glucose cotransporter 2 inhibitors (SGLT 2i), initially developed for the treatment of hyperglycemia in type 2 diabetes, have shown favorable effects on kidney and cardiovascular outcomes by promoting urinary glucose excretion and decreasing the risk for CV death and hospitalization for heart failure (HHF) among patients with type 2 diabetes in different population groups. 

Dapagliflozin, belonging to the class of SGLT 2 inhibitors is known to reduce the risk of kidney failure and heart failure in patients with chronic kidney disease. A study was conducted to assess the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes in both the group of individuals with diabetes and without diabetes. The study also included an evaluation of the underlying causes of Chronic Kidney Disease (CKD), such as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown causes.

DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomized trial. The enrolled subjects with a urinary albumin-to-creatinine ratio of 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25–75 mL/min per 1•73m² were divided into two groups. The treatment group was prescribed a once-daily dose of dapagliflozin (10 mg), while the control group was given a matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite, a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality.

The study lasting over five years showed that 68% of participants had a diagnosis of type 2 diabetes, out of which 14% had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes and without diabetes. The hazard ratio [HR] for the primary composite outcomes for the treatment and control group was reported as 0•64, and 0•50 respectively. A similar pattern was seen for the secondary outcomes, i.e., kidney-specific composite outcome (0•57 vs 0•51), cardiovascular death, hospital admission for heart failure (0•70 vs 0•79), and all-cause mortality (0•74 vs 0•52). Meanwhile, The effect of dapagliflozin therapy on the underlying causes of Chronic Kidney Disease, such as diabetic nephropathy (HR-0.63), glomerulonephritides (HR-0.43), ischaemic or hypertensive chronic kidney disease (HR-0.75), and chronic kidney disease of other or unknown cause (HR-0.58) was consistent for both primary and secondary outcomes. Hence, it can be concluded that dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease.

Reference: Wheeler DC et al., Lancet Diabetes Endocrinol. 2021 Jan;9(1):22-31. 

Doi: 10.1016/S2213-8587(20)30369-7.