Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (CREDENCE)
In the CREDENCE trial, canagliflozin reduced the risk of kidney failure and cardiovascular events in patients with type 2 diabetes and albuminuric chronic kidney disease, with a 30% lower relative risk of the primary renal-cardiovascular composite outcome.
Background
Type 2 diabetes is the leading cause of kidney failure worldwide, yet few effective long-term treatments existed beyond renin-angiotensin system blockade. Cardiovascular trials of SGLT2 inhibitors had suggested possible renal benefit, but dedicated kidney-outcome evidence in patients with established diabetic nephropathy was lacking. CREDENCE was designed to test canagliflozin specifically in this high-risk population.
Study design
This double-blind, randomized, placebo-controlled trial enrolled 4401 patients with type 2 diabetes, an estimated GFR of 30 to under 90 ml per minute per 1.73 m2, and albuminuria (urinary albumin-to-creatinine ratio greater than 300 to 5000), all treated with renin-angiotensin system blockade. Participants received canagliflozin 100 mg daily or placebo. The primary outcome was a composite of end-stage kidney disease, doubling of serum creatinine, or renal or cardiovascular death; the trial was stopped early after a planned interim analysis.
Key findings
Over a median follow-up of 2.62 years, the relative risk of the primary composite outcome was 30% lower with canagliflozin (hazard ratio 0.70, 95% CI 0.59 to 0.82; P=0.00001). The risk of end-stage kidney disease was 32% lower (hazard ratio 0.68, 95% CI 0.54 to 0.86; P=0.002). Canagliflozin also reduced the risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio 0.80, 95% CI 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio 0.61, 95% CI 0.47 to 0.80; P<0.001), with no significant difference in amputation or fracture rates.
Clinical implications
CREDENCE provided definitive evidence that canagliflozin protects the kidneys and heart in patients with type 2 diabetes and established nephropathy, beyond the modest reductions in HbA1c and blood pressure observed. The results re-established interest in therapies that reduce residual risk of diabetic kidney disease progression and helped position SGLT2 inhibition as a cornerstone of management alongside RAS blockade.
Category
Research
Source
New England Journal of Medicine
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