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An SGLT-2 inhibitor Shows Renoprotective Benefits

Apr 21, 2018
 

Subanalysis of CANVAS program shows slower progression of kidney disease, reduction in weight, reduction in A1c, and even drop in blood pressure.

The Janssen Pharmaceutical Companies of Johnson & Johnson announced an additional analysis from the landmark CANVAS Program showing INVOKANA®(canagliflozin) improved renal outcomes in people with type 2 diabetes mellitus (T2DM) with or at high risk for cardiovascular (CV) disease. This benefit was observed in people with both preserved and reduced kidney function, as measured by estimated glomerular filtration rate (eGFR) above or below 60 mL/min/1.73 m2.

A prespecified analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program by baseline kidney function was performed. These trials randomized patients with type 2 diabetes with or at high risk of cardiovascular disease to canagliflozin or placebo. Prespecified renal outcomes included urinary albumin: creatinine ratio (UACR), and composites of end-stage kidney disease (ESKD), renal death, and either 40% decline in estimated GFR (eGFR) or doubling of serum creatinine. Results were analysed according to kidney function (eGFR<60 vs ≥60 ml/min/1.73m2).

In the new analysis, canagliflozin reduced the urinary albumin to creatinine ratio (UACR), a key biomarker for chronic kidney disease, from baseline eGFR in patients with preserved and reduced eGFR by 17 percent and 23 percent, respectively. Canagliflozin also resulted in a relative risk reduction of the pre-specified composite endpoint (40 percent decline in eGFR, end-stage kidney disease or renal death) by 47 percent in patients with preserved eGFR and 24 percent in patients with reduced eGFR. Findings were similar when doubling of serum creatinine was substituted for 40 percent decline in eGFR in the renal composite. There was no difference in risk of serious adverse events with canagliflozin in the two patient subgroups and no new adverse events were observed during this additional analysis beyond those previously reported from the CANVAS Program.

George Bakris, M.D., Professor of Medicine and Director, Comprehensive Hypertension Center, University of Chicago Medicine added that, “Diabetic kidney disease remains the most common cause of end-stage renal disease worldwide, which underscores the need to further explore the potential renal protective effects of SGLT2 inhibitors….The new analysis adds to the body of evidence, which suggests canagliflozin could potentially improve renal outcomes for millions of people with type 2 diabetes and suggests this benefit can be observed in people who have preserved and reduced kidney function.” Bakris added that the CREDENCE trial was one reason behind wanting to conduct the current analysis. “Given that the CREDENCE trial is ongoing and is statistically powered for a primary renal outcome study using canagliflozin, we wanted to take a deeper look at the renal data from CANVAS to provide greater insight as to what the possible renal outcomes and safety profile may be at trial end of CREDENCE,” he noted.

“Although roughly one in three adults with diabetes develops diabetic kidney disease, there have been no significant advances in treatment for patients,” said James F. List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. “We are encouraged that canagliflozin could potentially provide much-needed benefit for those with diabetic kidney disease, and look forward to building further on this insight in CREDENCE, the fully recruited and first dedicated SGLT2 inhibitor trial evaluating renal and cardiovascular outcomes in people with type 2 diabetes and kidney disease.”

Among 10,142 participants, 2,039 (20.1%) had a baseline eGFR <60ml/min/1.73m2. Placebo-adjusted reduction in UACR from baseline was at least as large in patients with reduced vs preserved eGFR (-23% vs -17%,). The effect of canagliflozin on the composite outcome of 40% decline in eGFR, ESKD, or renal death was similar in patients with reduced and preserved eGFR. Findings were similar when doubling of serum creatinine was substituted for 40% decline in eGFR in the renal composite. There was no difference in risk of serious adverse events with canagliflozin in patients with reduced or preserved eGFR.

The CANVAS Program is the longest, largest and broadest completed clinical research program evaluating CV outcomes of any sodium glucose cotransporter 2 (SGLT2) inhibitor in people with T2DM to date. The CANVAS Program assessed the efficacy, safety and durability of canagliflozin in more than 10,000 patients with T2DM who had either a prior history of CV disease or at least two CV risk factors. Data from the integrated analysis of the CANVAS and CANVAS-R trials were presented last year in a special symposium at the American Diabetes Association 77th Scientific Sessions and simultaneously published in The New England Journal of Medicine.

Practice Pearls:

  • The renoprotective benefits of canagliflozin appear similar in people with normal and reduced eGFR.
  • Canagliflozin reduced the urinary albumin to creatinine ratio (UACR), a key biomarker for chronic kidney disease, from baseline eGFR in patients with preserved and reduced eGFR by 17 percent and 23 percent, respectively
  • Canagliflozin could potentially improve renal outcomes for millions of people with type 2 diabetes

These data were presented at the 2018 National Kidney Foundation’s Spring Clinical Meetings (abstract #253) in Austin, TX.