SGLT2 inhibitors will become more popular with the combined CANVAS and CANVAS-RENAL studies showing the drugs decreased the risk of cardiovascular events in patients with type 2 diabetes.

The landmark research, presented recently at the American Diabetes Association’s Scientific Sessions in San Diego, suggests the sodium-glucose cotransporter-2  (SGLT2) inhibitors will move up the line of treatment options for patients with diabetes and an increased risk of cardiovascular disease.

Co-author Professor Vlado Perkovic, executive director of the George Institute for Global Health, told the limbic the findings confirmed those of the EMPA-REG Outcome study.

“There was a lot of uncertainty that the EMPA-REG results were real but in CANVAS we found not only cardiovascular safety but also benefit in terms of a decreased risk of the major cardiovascular end points,” he said.

The study found significantly fewer primary outcome events – a composite of death from cardiovascular causes, nonfatal myocardial infarction and nonfatal stroke – in the treated group compared to controls (26.9 v 31.5 per 1,000 patient years).

There was a non-significant trend towards benefit from canaglifloxin in all individual components of the composite outcome.

There was also a 40% reduction in hospitalisations for heart failure, Professor Perkovic said.

Renal outcomes were also improved with canaglifloxin as measured by a composite outcome of a sustained 40% reduction in eGFR, need for renal replacement therapy, or death from renal causes (5.9 v 9.0 per 1,000 patient years); and less progression (89.4 v 128.7 per 1,000 patient years) and more regression (293.4 v 187.5 per 1,000 patient years) of albuminuria.

“This is the biggest treatment effect for protecting the kidney which is very exciting,” he said.

Professor Perkovic, a nephrologist, added the ongoing CREDENCE study would provide evidence on whether canaglifloxin could also prevent dialysis in patients with type 2 diabetes and established kidney disease.

On the downside, CANVAS and CANVAS-R found a higher rate of toe, foot or leg amputations with canaglifloxin compared to placebo (6.3 v 3.4 events per 1,000 patient years; hazard ratio 1.97).

Professor Perkovic said the new finding highlighted the value of the long duration study. He said people with a previous amputation, poor circulation to the feet and those with neuropathy would be most at risk.

CANVAS but not CANVAS-Renal also found a higher rate of fractures (15.4 v 11.9 per 1,000 patient years overall).

“This is the first analysis of this trial and there is much more data to come but we can we can now say clearly that this class of drug has cardiovascular benefits. More specific studies on heart failure and the kidney are still to come.”