The CREDENCE trial: The effect of canagliflozin on renal function [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. In this study, a composite of end-stage kidney disease, double of serum creatinine, and renal or cardiovascular death was significantly lower in diabetic patients taking canagliflozin (43.2%) as compared to a placebo (61.2%).

2. Cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization rates were also lower in the canagliflozin group.

Original Date of Publication: June 2019

Study Rundown: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that canagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is superior to placebo in patients with type 2 diabetes in preventing renal dysfunction. The canagliflozin group had significantly lower rates of the primary composite outcome of end-stage kidney disease, double of serum creatinine, and renal or cardiovascular death as well as each outcome individually when compared to controls. Cardiovascular outcomes including cardiovascular death, myocardial infarction, and stroke were also significantly lower in the study group. Amputation and fracture rates did not differ between groups. The trial was limited in that it was stopped at interim analysis at recommendation of the safety monitoring committee. Although, previous large trials of SGLT2 inhibitors suggest that effect size was likely not overestimated due to trial interruption. In summary, the CREDENCE trial is a novel demonstration of the renal-protective effects of canagliflozin in patients with type 2 diabetes.

Click to read the study in NEJM

In-Depth [randomized control trial]: In the CADENCE trial, patients with type 2 diabetes and chronic kidney disease were randomized to either treatment with canagliflozin (n = 2,202) or treatment or placebo (n = 2,199). The trial was double blinded to reduce risk of bias and outcomes were adjudicated by blinded independent adjudication committees. In patients in the canagliflozin group, the primary composite end point of end-stage kidney disease, a doubling of serum creatinine level, and renal or cardiovascular death was significantly lower than in controls (HR 0.70; 95%CI 0.59-0.82). Cardiovascular death, myocardial infarction, stroke, and hospitalization (HR 0.68; 95%CI 0.54-0.86) as well as hospitalization for heart failure (HR 0.61; 95%CI 0.47-0.80) were also significantly lower in the study group. Although, risk of amputation or fracture did not differ between groups.

Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019 Jun 13;380(24):2295–306.

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