Rajiv Agarwal, MD
Indiana University School of Medicine, Indianapolis, IN, USA Meg J. Jardine, MD
The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia Bruce Neal, MD
The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia;
Epidemiology and Biostatistics, Imperial College London, London, UK Kenneth W. Mahaffey, MD
Stanford University School of Medicine, Stanford, CA, USA Bernard Zinman, MD
University of Toronto, Toronto, ON, Canada
In cardiovascular (CV) trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors, exploratory results have suggested that these drugs may improve renal outcomes in patients with type 2 diabetes.
The CREDENCE (Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation) trial evaluated the effects of canagliflozin on renal outcomes in patients with type 2 diabetes and albuminuric chronic kidney disease (CKD).
In several trials performed to meet regulatory requirements for CV safety, reductions in CV events with SGLT2 inhibitors have been found. Secondary and exploratory analyses of these trials suggested that SGLT2 inhibition might improve renal outcomes; however, relatively few patients reached end-stage kidney disease and patients in these trials were at low risk for kidney failure. Many renal effects of SGLT2 inhibition have been proposed.
To assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment relative to placebo in patients with type 2 diabetes mellitus, Stage 2 or 3 CKD, and macroalbuminuria, who are receiving standard of care including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).
Double-blind, randomized trial, in 4,401 patients with type 2 diabetes and albuminuric CKD to receive canagliflozin (n=,2202; 100 mg/day) or placebo (n=2,199).
All patients had an estimated glomerular filtration rate (eGFR) of 30 to <90 ml/min/1.73 m2 and albuminuria (ratio of urine albumin (mg) to creatinine (g), >300 to 5,000) and were treated with renin–angiotensin system blockade.
Primary outcome measure
The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained eGFR of <15 ml/min/1.73 m2), a doubling of serum creatinine level, or death from renal or CV causes.
The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (HR 0.70; 95% CI, 0.59 to 0.82; P = 0.00001).
In the canagliflozin group, the relative risk of the renal-specific composite of end-stage kidney disease, a doubling of creatinine level, or death from renal causes was lower by 34% (HR 0.66; 95% CI, 0.53 to 0.81; P <0.001) than in the placebo group, and the relative risk of end-stage kidney disease was lower by 32% (HR 0.68; 95% CI, 0.54 to 0.86; P=0.002) (Figure).
The canagliflozin group also had a lower risk of CV death, myocardial infarction, or stroke (HR 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization for heart failure (HF 0.61; 95% CI, 0.47 to 0.80; P<0.001).
The safety profile was consistent with previous studies on canagliflozin, with no difference vs. placebo for rates of fracture or amputation.
Jose C. Florez, MD, PhD
Chair, ADA Scientific Sessions Meeting Planning Committee
The 79th American Diabetes Association’s Scientific Sessions were held in San Francisco, California from June 7-11, 2019. The meeting was attended by over 15,000 professional attendees from 115 countries, … [ Read all ]
Presented by: Alison B. Evert, MD; Janice MacLeod, MA, RDN, CDE; William S. Yancy, Jr., MD, MHS; W. Timothy Garvey, MD; Ka Hei Karen Lau, MS, RD, LDN, CDE; Christopher D. Gardner, PhD; Kelly M. Rawlings, MS