Diabetes, SGLT2's and Related Cardiovascular Outcome Trials

Lori Berard, RN, DCE, Diabetes Educator, Nurse Consultant, reviews SGLT2's mechanism of action and benefits and discusses how recent cardiovascular outcome trials.

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Lori Berard, RN, DCE, Diabetes Educator, Nurse Consultant, reviews SGLT2's mechanism of action and benefits and discusses how recent cardiovascular outcome trials.
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Featuring Lori Berard, RN, DCE, Diabetic Nurse Educator

Duration: 3 minutes, 38 second

It’s really important for people to understand how an SGLT2 inhibitor works. SGLT2 transporters pick up glucose from the urine and bring it back into the body. Unfortunately, when you live with diabetes there’s an up regulation and you store more glucose than you need.

What an SGLT2 inhibitor does is blocks that reabsorption in the urine, so in the distal tubule of the kidney, after it’s already cleared through the glomerulus and is filtered and ready to go out of the body, unfortunately the body doesn’t let it go. It sucks it back in.

So by blocking that reabsorption of glucose from the urine, we can actually lower glucose. We see that patients excrete glucose in the urine, which lowers blood sugar levels, that glucose equals calories, we know that somewhere between 70 and 120 grams of glucose is lost per day.

When they lose glucose and calories, there’s a potential for weight loss, and then, there’s also fluid that goes out with the glucose, somewhere between 250 to 400 cc a day. So that might mean that in fact there can be also blood pressure lowering.

We can only use SGLT2 glucose inhibitors for glucose lowering however, in individuals who have functioning kidneys. So we know that the indication is for people who have eGFRs over 60, and it isn’t so much that they’re harmful, it’s more so that they don’t really work when renal function declines.

So choosing the patient appropriately, you’ll look for someone in whom the benefit of glucose lowering, perhaps some weight loss, blood pressure lowering, would be essential. And then you look at their renal function, and then you also make sure that they’re not at risk for volume depletion, because those individuals may not be the best candidate.

When we think about this class of medication, it’s important to have a benefit-risk discussion with individuals, and we know that they lower glucose, they don’t cause hypoglycemia, and they have very minimum weight. We also know there’s an added benefit of blood pressure.

But more recently, what’s been really exciting around the SGLT2 inhibitors, is the new evidence that’s been created by cardiovascular outcome trials. Remembering that we do cardiovascular outcome trials in very high risk people with diabetes, typically those who have already had a previous cardiovascular event.

FDA, EMA and even Health Canada has mandated that we show all new drugs for diabetes to be safe, that they don’t cause harm. So we were very surprised when EMPA-REG in September 2015 came out and showed us benefit of 14% reduction in major adverse cardiovascular events and hospitalization for heart failure. Followed up June of this year, we saw the exact same MASE reduction with the CANVAS trial.

So suddenly we are now moving from talking about medications that are managing glucose to those that are managing cardiovascular risk. I think as health care professionals it’s really important for us to stay up to date on all of this evolving evidence.

So my challenge to you would be that you consider informing yourself about cardiovascular outcome trials, learning about real world evidence and also informing yourself of the advances that we’re learning about the class of SGLT2 inhibitors, beyond glucose lowering.

Presenter: Lori Berard, Nurse, Winnipeg, MB

Local Practitioners: Nurse

This content is for informational purposes only, and is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified healthcare professional with any questions you may have regarding a medical condition.