"Dapagliflozin in Patients with Chronic Kidney Disease". The New England Journal of Medicine. 2020.
Links to original sources: Wiki Journal Post Full Journal Article
In patients with chronic kidney disease, with or without type 2 diabetes, does dapagliflozin improve renal outcomes and reduce cardiovascular mortality?
In patients with chronic kidney disease, dapagliflozin significantly reduced the risk of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes, regardless of diabetes status.
The DAPA-CKD trial demonstrated that dapagliflozin, an SGLT2 inhibitor, slowed the progression of kidney disease and improved survival among patients with chronic kidney disease (CKD), either with or without type 2 diabetes. The benefits of SGLT2 inhibitors on kidney outcomes were previously established predominantly in type 2 diabetic populations, and this trial extended those findings to a broader CKD population.
As of 2017, treatment guidelines for diabetes and CKD primarily recommended the use of ACE inhibitors or ARBs to slow kidney disease progression. The DAPA-CKD trial findings support the expansion of SGLT2 inhibitors as a therapeutic option for a wider CKD population.
Multicenter, double-blind, randomized, placebo-controlled trial N=4,304 patients with chronic kidney disease Intervention: Dapagliflozin (10 mg once daily) (n=2,152) Comparison: Placebo (n=2,152) Median follow-up: 2.4 years Primary outcome: Composite of ≥50% sustained eGFR decline, end-stage kidney disease, or death from renal or cardiovascular causes
Adults with or without type 2 diabetes, eGFR of 25 to 75 ml/min/1.73m2, and urine albumin-to-creatinine ratio of 200 to 5,000 Exclusion Criteria: Type 1 diabetes, polycystic kidney disease, certain glomerulonephritides, recent immunotherapy for primary or secondary kidney disease
Participants were randomized to receive dapagliflozin (10 mg once daily) or placebo.
Primary Outcome: The primary composite outcome occurred in 9.2% of the dapagliflozin group and 14.5% of the placebo group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001; number needed to treat, 19). Secondary Outcomes: Reduction in risk was observed for a composite of heart failure hospitalizations or cardiovascular death (hazard ratio, 0.71; P=0.009), and all-cause mortality was significantly lower in the dapagliflozin group (hazard ratio, 0.69; P=0.004).
The trial was stopped early due to efficacy, potentially reducing the statistical power for some secondary outcomes. Also, reversibility of the initial decline in eGFR after stopping dapagliflozin was not assessed post-trial.
Trial was funded by AstraZeneca.
Detailed trial information and data sharing statement available at NEJM.org.