Type 2 diabetes drug a ‘game changer’

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.”

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  1. Linda

    Good drug. I was diagnosed with type 2 Diabetes and put on Metformin on June 26th, 2016. I started the ADA diet and followed it 100% for a few weeks and could not get my blood sugar to go below 140. Finally i began to panic and called my doctor, he told me to get used to it. He said I would be on metformin my whole life and eventually insulin. At that point i knew something wasn’t right and began to do a lot of research. Then I found Lisa’s diabetes story (google ” HOW EVER I FREED MYSELF FROM THE DIABETES ” ) I read that article from end to end because everything the writer was saying made absolute sense. I started the diet that day and the next morning my blood sugar was down to 100 and now i have a fasting blood sugar between Mid 70’s and the 80’s. My doctor took me off the metformin after just three week of being on this lifestyle change. I have lost over 30 pounds and 6+ inches around my waist in a month. The truth is we can get off the drugs and help myself by trying natural methods

  2. Curtis Watson

    Aren’t these the reasons Invokana got deleted in Aus toward the end of last year? Not a favourable profile compared with other SGLT2-i ..
    Anyway it is still amazing to me, and one of the reasons why I love pharmacology and pathology. Here’s a drug that reduces glucose reabsorption in the kidneys, and that causes the body to have an increased risk of fractures and amputations.. what the? And patients ask me why cant big pharma create a drug without any side effects. Cue Sir Derrick Dunlop someone.

    • Jarrod McMaugh

      From memory Invokana was voluntarily removed from the PBS by the applicant because the pricing was indexed against DPP4s

      Why would you retain PBS pricing if it isn’t adequate?

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