Canagliflozin reduces risk for CVD, kidney disease in adults with type 2 diabetes

Anti-diabetes drug also 'lessens kidney, heart disease' risk

Diabetes can cause a narrowing of blood vessels between the knee and the toes, causing a decrease in oxygen circulation that prevents healing An ...

CanagliflozinPatients with type 2 diabetes at high risk for cardiovascular disease assigned the SGLT2 inhibitor canagliflozin showed a 33% reduction in risk for hospitalization for heart failure and were 40% less likely to experience renal decline vs. those assigned placebo, according to findings from the integrated CANVAS study presented at the American Diabetes Association Scientific Sessions. In a randomized, double blind, placebo-controlled trial conducted across 30 countries, researchers also noted that participants assigned canagliflozin (Invokana, Janssen) were twice as likely to experience an amputation, primarily at the toe or metatarsal, compared with those receiving placebo.

“The key question is: How do the risks and the benefits balance up?” Bruce Neal, MB, ChB, PhD,scientific director at The George Institute for Global Health, said during a press conference announcing the findings. “For 1,000 individuals treated [with canagliflozin] for 5 years … there would be 23 fewer deaths from vascular disease, 17 fewer hospitalizations for heart failure and 16 fewer serious declines in renal function. By contrast, there would be 15 more amputations, and 10 of these would be at the toe or forefoot and five [would be] above the ankle.”

Study design, results

For the integrated CANVAS program, Neal and colleagues analyzed data from two trials involving 10,142 participants with type 2 diabetes and high CV risk, CANVAS (n = 4,330) and CANVAS-R (n = 5,812). The mean age for both trials was 63 years; 35.8% were women; mean duration of diabetes was 13.5 years; mean HbA1c, 8.2%; mean estimated glomerular filtration rate was 76.5 mL/min/1.73 m²; median urinary albumin to creatinine ratio was 12.3. Researchers randomly assigned participants in CANVAS to 100 mg or 300 mg canagliflozin or placebo; participants in CANVAS-R received an initial dose of 100 mg canagliflozin daily with an optional increase to 300 mg at week 13, or matching placebo. Follow-up occurred every 3 months for the first year and at 6-month intervals thereafter, with follow-up by telephone between in-person appointments. Serum creatinine and eGFR rate were measured at least every 26 weeks in both trials; urinary albumin to creatinine ratio was assessed every 26 weeks in CANVAS-R and at week 12 and annually in CANVAS. Primary outcome was a composite of death from CVD, nonfatal myocardial infarction and nonfatal stroke. Within the cohort, 9,734 participants completed the trials; mean follow-up for both trials was 188.2 weeks, with a longer follow-up period in the CANVAS study (mean, 295.9 weeks). At baseline, 65.6% of participants had a history of CVD, 22.6% had microalbuminuria and 7.6% had macroalbuminuria.


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