Physicians' Academy for Cardiovascular Education

Fewer CV events but higher risk of amputation with SGLT2 inhibitor in T2DM patients

Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

Literature - Neal B, Perkovic V, Mahaffey KW, et al, for the CANVAS Program Collaborative Group - NEJM 2017; published online ahead of print

Background

SGLT2 inhibitors have favorable effects on glycemia, blood pressure, body weight, intrarenal hemodynamics, and albuminuria, and they may also reduce the risk of serious CV complications, kidney disease, and death [1-3].

The CANVAS program consisted of 2 studies: The Canagliflozin Cardiovascular Assessment Study (CANVAS) was set up to evaluate CV safety, including kidney and other safety outcomes, such as genitourinary infection, diabetic ketoacidosis, and fracture. CANVAS–Renal (CANVAS-R) was designed as a second CANVAS-like trial with similar design to CANVAS, to be analyzed jointly with CANVAS, to meet a post-approval CV safety commitment to regulatory agencies. CANVAS-R therefore also assessed effects on albuminuria.

This is an integrated analysis of CANVAS (n=4330) and CANVAS-R (n=5812) on data of T2DM patients with elevated CV risk, randomized to canagliflozin (300 or 100 mg in CANVAS, 100 mg in CANVAS-R) or placebo, in addition to background therapy [4-6]. Patients were followed for a mean of 295.9 weeks in CANVAS and 108.0 weeks in CANVAS-R.

Main results

Conclusion

In the CANVAS trial program, diabetic patients with elevated CV risk treated with canagliflozin had a significantly lower risk of CV death, non-fatal MI, or non-fatal stroke compared with those who received placebo, but a higher risk of amputation and fractures.

References

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Find this article online at NEJM