Impact of Canagliflozin on Renoprotection in T2DM

December 19, 2018

Will SGLT2 inhibitor canagliflozin prove renoprotective in T2DM patients? CANVAS study authors sought to find out.

While studies have been conducted on the possible renoprotective function for sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as the EMPA-REG OUTCOME trial, these studies analyzed a limited number of outcomes. So, authors of a new study sought to determine the impact of canagliflozin on a range of renal outcomes in patients with T2DM and a high risk for cardiovascular events. What were the results? And how will the results impact clinical practice? Click through our slideshow above to find out more.

SGLT2 Inhibitors and Renoprotection: What’s the Evidence? Authors of the CANVAS study sought to determine the impact of canagliflozin on a range of renal outcomes in T2DM patients who were at a high risk of CV events.

CANVAS: Long-term Impact of Canagliflozin on Renal Outcomes.³ CANVAS consisted of 2 double-blind, masked randomized trials that looked at canagliflozin vs placebo in 10 142 T2DM patients with high CV risk at 667 centers in 30 countries. Patients were randomized to receive 300 mg canagliflozin, 100 mg canagliflozin, or placebo daily. Mean follow-up was 3.6 years.

Benefits Seen in Broad Range of Renal Outcomes. Kidney function stabilized for canagliflozin vs placebo. There was a 47% lower risk of sustained doubling of serum creatinine, end-stage kidney disease, and death from renal causes; an 18% reduction in albuminuria; a 20% lower risk of new-onset albuminuria; and a slower annual eGFR decline. Serious renal-related adverse events were similar for canagliflozin vs placebo.

Clinical Implications. CANVAS study supports using SGLT2 inhibitors for renoprotection in T2DM patients. Results of the study are not likely to lead to new indications for kidney disease prevention with SGLT2 inhibitors. CREDENCE is the first dedicated trial of SGLT2 inhibitors and renal outcomes with final data analysis pending.

Take Home Points. CANVAS trial suggests stabilization of kidney function with canagliflozin. Over 3.6 years, canagliflozin was linked to lower composite of renal events, less albuminuria, slower annual eGFR decline in T2DM patients with high CV risk, and relatively well preserved renal function. Further study is needed to support renoprotection indication for SGLT2 inhibitors.

References:

1. EMPA-REG OUTCOME Investigators, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323-334.
2. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-657.
3. Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: Results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018;6:691-704.