Diabetes wreaks havoc on the kidneys – it is currently the leading cause of renal failure in the world. A relatively new class of diabetic drugs, called sodium-glucose cotransporter protein 2 (SGLT2) inhibitors has been shown to improve blood sugar control and improve cardiovascular outcomes. Unlike other diabetic drugs, the SGLT2 inhibitors work by blocking the reuptake of glucose in the kidneys, causing the glucose to be excreted directly into the urine. Previous trials done for cardiovascular outcomes showed trends toward improved renal outcomes, and these data led to the current trial, specifically evaluating kidney disease and the use of SGLT2 inhibitors.
Dr. Vlado Perkovic and colleagues reported their findings in the June 13, 2019 issue of The New England Journal of Medicine. The trial is called CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation). They enrolled 4401 patients with type 2 diabetes and preexisting chronic kidney disease. 2202 patients were randomly assigned to receive canagliflozin 100 mg orally once per day, and 2199 patients to receive a placebo. All patients were required to take either an angiotensin-converting-enzyme inhibitor or angiotensin II-receptor blocker for at least four weeks prior to randomization. End-stage renal disease outcomes (dialysis, transplantation, or sustained GFR below 15 ml/min) were compared between groups.
At a mean follow-up of approximately 2.6 years, the trial was ended (early) because of a significant reduction in renal outcomes in the canagliflozin group compared with the placebo group (43.2 and 61.2 per 1000 patient-years, respectively; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). Investigators also noted improved cardiovascular outcomes, which included a lower risk of cardiovascular death, myocardial infarction (MI), and stroke.
There was no significant difference in the rate of adverse events reported between the groups, including rates of amputation or fracture.
The study was funded by Janssen Research and Development.
Comments
- approximately four hundred million people worldwide have diabetes, at least 40% will go on to develop renal injury
- there has been no significant new renal treatment/prevention in the past two decades since the development of angiotensin-converting-enzyme inhibitors (ACE inhibitors) and angiotensin II-receptor blockers (ARBs)
- although this trial enrolled only those with preexisting renal disease (caveat – those with severe renal disease were excluded), a risk reduction of 30% is very significant, especially with concomitant improvement in cardiovascular outcomes as noted
- look for continuing updates to the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) guidelines