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Canagliflozin for Type 2 Diabetes - reduces cardiovascular events.

Canagliflozin reduces major adverse cardiovascular events (MACE) in patients with T2DM.

Big paper in the NEJM, (the trials sponsored by Janssen Research, but independently authored), showing a reduction in a composite of:

  • death from cardiovascular causes,

  • non-fatal myocardial infarction

  • non-fatal stroke

with canagliflozin.

It was a small effect, (in medical terminology only just significant) but relevant to many patients with diabetes; the trials were really to prove CV safety, which they did handsomely.

There were more distal amputations with canigliflozin, albeit small numbers of events, so this needs some thinking! Certainly we have to be cautious in its use in patients at risk of amputation.

Canagliflozin is one of the newer agents for diabetes mellitus - part of the class of sodium glucose co-transporter 2 (SGLT2) inhibitors and they have a really interesting mechanism of action. Glucose is a small molecule and it passes out through filtration in the kidney quite freely, but as it is so valuable there are specific transporters right after that filtration to bring it back into the body, and the transporter that's relevant here is SGLT2. By blocking it we allow some glucose to leave the body, improving the effects of the hyperglycaemia, with a mechanism to lose weight (the patient is losing energy in the glucose), the glucose generally takes some water with it, so acts like a diuretic, helping the blood pressure. The benefits on blood pressure and weight were seen in the trials too and are reported in the paper.

All of these potential benefits and the interesting mechanism means nothing if the drug does not help cardiovascular problems in diabetes. To demonstrate that it was as good as current therapy these trials were done, and it is always good to see that they are not only as good, but better than what we have! So these new agents are finding their place.

Diabetes is a disease of early and widespread cardiovascular disease - that causes early avoidable death, or avoidable harm, such as heart attacks, strokes, peripheral vascular disease, renal failure, nerve damage and damage to the eyes. Good diabetes care reduces the risk of death and harm.

The best tip is to avoid diabetes by paying attention to diet and exercise right throughout life, and if one does get diabetes, pay attention to diet and exercise. Keep the glucose well controlled, maintain a good blood pressure and control the lipids, these things very often with medications.

And if you smoke, stop. It's one of the most effective things to reduce ones risk of cardiovascular disease.

Here's the article -

and it is not behind a paywall. Please share if you want and/or comment.

There can be a tendency to think every new treatment is better, but we have really very well tried and tested treatments for diabetes - diet and exercise, metformin, the sulphonyureas, DPP-IV inhibitors, injectable GLP-1 agonists, acarbose, prandial glucose modulators, insulin and SGLT2 inhibitors.

If you have diabetes decide on your own priorities for management with your doctor.

Dr Philip Kelly is an experienced endocrinologist, diabetologist and general physician dealing with cardiovascular complications of diabetes in his routine work, he helps patients get the right treatment for their diabetes and their lifestyle.

The discussion here is about the results in one paper, it is not personal medical advice.

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