Canagliflozin protects Heart and Kidneys – CREDENCE Trial

Canagliflozin is sodium–glucose cotransporter 2 (SGLT2) inhibitor used in the treatment of type 2 diabetes mellitus. CREDENCE Trial [1] has shown that Canagliflozin provides both cardiovascular and renal protection in patients with type 2 diabetes mellitus.

CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial was a double blind randomized trial comparing Canagliflozin 100 mg daily with placebo in type 2 diabetes with albuminuria and chronic kidney disease. They were also treated with renin–angiotensin system blockade.

They found that risk of both kidney failure and cardiovascular events were lower in canagliflozin group at a median follow-up of 2.62 years.

Renal specific composite end point was end-stage kidney disease, doubling of serum creatinine level or death from renal cause. Relative risk of the composite end point was lower by 34% (P<0.001) in the canagliflozin group. Relative risk of end-stage renal disease was lower by 32% (P=0.002).

There was a lower risk of cardiovascular death, myocardial infarction, or stroke (P=0.01). Risk of hospitalization for heart failure was also lower (P<0.001).

Interestingly there was no increase in the rates of rates of amputation or fracture in the study group. An important concern raised in the CANVAS program (Canagliflozin Cardiovascular Assessment Study) for Canagliflozin was a potential risk of higher rates of amputation, primarily at the level of the toe or metatarsal [2].

Reference

1. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris GL, Bull S, Cannon CP,  Capuano G, Chu P, de Zeeuw D, Greene T,  Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; for the CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. April 14, 2019. DOI: 10.1056/NEJMoa1811744
2. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657.