A relatively new drug has been found to greatly reduce risk of cardiovascular and kidney disease – though it comes with risks of its own
Canagliflozin (Invokana) is a SGLT2 inhibitor that works by blocking the body’s reabsorption of sugar or glucose, resulting in a drop in glucose levels.
Results from two trials run across 30 countries, including more than 10,000 participants, revealed participants in the canagliflozin group had fewer instances of death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke (26.9 vs 31.5 participants with an event per 1000 patient-years; hazard ratio, 0.86; 95% CI, 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority).
Participants being treated with canagliflozin were also 40% less likely to suffer from serious kidney decline.
Results showed that for every 1,000 people treated with canagliflozin for five years, it would prevent:
- 23 deaths from cardiovascular causes, heart attack or stroke;
- 16 admissions to hospital for heart failure; and
- 17 events of serious kidney decline.
However, of concern is that participants in the intervention arm were twice as likely to suffer from amputation of toes, feet or legs as those in the placebo group.
For every 1,000 people treated with canagliflozin for five years, researchers estimate it would cause 15 amputations, including five very serious ones (above the ankle) and 10 toe or metacarpal related.
“Amputations are definitely something to be concerned about,” lead author Professor Bruce Neal, from The George Institute for Global Health, told the AJP.
“What we need to do is try to figure out who is most likely to benefit from this drug, and those who is more likely to be harmed.”
Prescribers should be aware of prescribing canagliflozin to patients at higher risk of amputation, such as those with a history of amputation, peripheral vascular disease or other related conditions, says Professor Neal.
“These are people you wouldn’t want to give this drug, or in fact any drug in this class,” he says.
“We don’t know why there was an increased risk of amputation. Further work is needed in this area. But for now we urge caution in prescribing this drug to people at increased risk of suffering amputation.”
A higher rate of fractures was also associated with canagliflozin than in the intervention arm, but only in an interim analysis in one of the trials.
Since an increase in bone fractures has also been described in previous research in relation to the drug, Professor Neal suggests prescribers should also be wary of patients at high risk of fractures.
Despite these risks, the positive cardiovascular findings published in the New England Journal of Medicine have major implications for the treatment of type 2 diabetes, say researchers from The George Institute.
“Coronary heart disease is the biggest killer by far for people with type 2 diabetes,” says Professor Neal.
“Our findings suggest that not only does canagliflozin significantly reduce the risk of heart disease, it also has many other benefits too. We found it also reduced blood pressure and led to weight loss.”
In Australia, around 65% of all cardiovascular deaths occur in people with diabetes or pre-diabetes, and diabetes is also the leading cause of end-stage kidney disease, says The George Institute.
“This is really a game changer in the treatment of type 2 diabetes,” says co-author Professor Vlado Perkovic, Executive Director of The George Institute Australia.
“It not only reduces the risk of heart disease, it also provides real protection against kidney decline which affects many people with diabetes.”