Canagliflozin Significantly Reduces Cardiovascular Risks that Affect T2DM Patients

Compared to placebo, canagliflozin reduced the risk of the composite primary endpoint (cardiovascular mortality, nonfatal MI, nonfatal stroke) by 14% (HR: 0.86; 95% CI: 0.75-0.97).

This article is part of MPR‘s coverage of the American Diabetes Association’s 77th Scientific Sessions (ADA 2017), taking place in San Diego, CA. Our staff will report on medical research and technological advances in diabetes and diabetes education, conducted by experts in the field. Check back regularly for more news from ADA 2017.

Compared to placebo, canagliflozin (Invokana; Janssen) significantly reduced the combined risk of cardiovascular death, myocardial infarction (MI), and nonfatal stroke in patients with type 2 diabetes mellitus (T2DM). These findings were presented at the American Diabetes Association 77th Scientific Session in San Diego, CA and were also published in the New England Journal of Medicine.

The CANVAS program, which is comprised of two similar trials (CANVAS and CANVAS-R), assessed the efficacy, safety, and durability of canagliflozin in >10,000 T2DM patients with a history of cardiovascular disease, or at least two cardiovascular risk factors. Compared to placebo, canagliflozin reduced the risk of the composite primary endpoint (cardiovascular mortality, nonfatal MI, nonfatal stroke) by 14% (HR: 0.86; 95% CI: 0.75–0.97). Specifically, canagliflozin reduced the risk of nonfatal MI by 15% (HR: 0.85; 95% CI: 0.69–1.05), cardiovascular death by 13% (HR: 0.87; 95% CI: 0.72–1.06), and nonfatal stroke by 10% (HR: 0.90; 95% CI: 0.71–1.15).

“The CANVAS results are important because they show clear benefit of canagliflozin over current standard-of-care treatments,” said Bruce Neal, MB, ChB, PhD, principal investigator of the CANVAS and CANVAS-R trials, Professor of Medicine, University of New South Wales Sydney, and Senior Director, The George Institute for Global Health. “Furthermore, the CANVAS Program showed consistent reductions across all components of the primary study outcome – CV death, MI and stroke – indicating efficacy of canagliflozin for all the main CV risks likely to affect patients with diabetes.” 

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In addition, treatment with canagliflozin lowered the risk of hospitalization for heart failure by 33% (HR: 0.67; 95% CI: 0.52–0.87) and demonstrated potential renal protective effects, delaying progression of albuminuria and reducing the risk of clinically important renal composite outcomes by 40% (HR: 0.60; 95% CI: 0.47–0.77). The effect of canagliflozin on renal outcomes in patients with T2DM and renal disease will be further evaluated in the CREDENCE study.

With regards to adverse events, an increased risk of amputations was noted in the canagliflozin arm in both CANVAS and CANVAS-R (6.3 vs. 3.4/1000 patient-years; HR: 1.97); patients with prior history of amputation or peripheral vascular disease were found to be at greatest risk. Overall adverse events from these trials appeared to be consistent with previous findings. 

Invokana, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM.

Click here to view an infographic detailing the CANVAS program.

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