Study Shows SGLT2 Inhibitor Protects Against Kidney Failure and Cardiovascular Events

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Patients with type 2 diabetes and kidney disease who received the SGLT2 inhibitor canagliflozin, had a lower risk of kidney failure and cardiovascular events as compared to a placebo group, a new study shows.

Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that is designed to lower blood sugar in patients with type 2 diabetes mellitus. Previous trials have suggested, buy not definitively, that it can protect the kidneys of diabetic patients.

Type 2 diabetes is a leading cause of kidney failure, but there are few effective long-term treatments. In this double-blind, randomized trial published in the New England Journal of Medicine, patients who received canagliflozin had a lower risk of end-stage kidney disease, hospitalization for heart failure, and the composite of cardiovascular death, myocardial infarction, or stroke.

"These results indicate that canagliflozin may be an effective treatment option for renal and cardiovascular protection in patients with type 2 diabetes with chronic kidney disease," wrote the authors who were led by Vlado Perkovic, Ph.D., of the University of New South Wales Sydney, Australia.

THE STUDY

The trial included 4,401 patients (mean age 63, 33.9 percent women) from 34 countries. The patients had an average glycated hemoglobin value of 8.3 percent, an estimated glomerular filtration rate (GFR) of 56.2 ml per minute per 1.73 m2, and the median urinary albumin-to-creatinine ratio was 927 (albumin measured in milligrams and creatinine in grams). They were at high risk for cardiovascular outcomes, with cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure, which occurred in 13.8 percent of the population over 2.62 years.

Patients with type 2 diabetes and albuminuric chronic kidney disease were randomly assigned to receive canagliflozin at 100 mg daily or a placebo.
The primary outcomes included end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of less than 15 ml per minute per 1.73 m2); a serum creatinine level that doubled, or death from renal or cardiovascular causes.

By the trial’s end, the canagliflozin treatment group experienced a reduction of .31 percentage points for glycated hemoglobin at 13 weeks, but throughout the trial the average tapered to .25 percentage points. The treatment group also experienced a decrease in systolic blood pressure (by 3.30 mm Hg), diastolic blood pressure (by 0.95 mm Hg), and body weight (by 0.80 kg) and the urinary albumin-to-creatinine ratio was lower by 31 percent during the 2.62 follow-up years.

“The significantly lower rates of cardiovascular outcomes, including the composite of cardiovascular death, myocardial infarction, or stroke, in the canagliflozin group in our trial are consistent with those observed with canagliflozin in the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, despite the smaller differences in glycemic control. The EMPA-REG OUTCOME trial also showed that empagliflozin was superior to placebo, and the DECLARE–TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) trial showed that dapagliflozin was noninferior to placebo for this composite outcome. The reduction in hospitalization for heart failure seen in our trial is consistent with results of other trials of SGLT2 inhibitors,” the authors wrote.

DISCLOSURES
The trial was funded by Janssen Research and Development.

REFERENCE
Vlado Perkovic, M.B., B.S., Ph.D., Meg J. Jardine, M.B., B.S., Ph.D., Bruce Neal, M.B., Ch.B., Ph.D., et al. "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy," New England Journal of Medicine. April 14, 2019. DOI: 10.1056/NEJMoa1811744