COMMENTARY

For the Good of Your Patients, Continue Using SGLT2 Inhibitors

Per-Henrik Groop, MD, DMSc

Disclosures

November 14, 2018

The SGLT2 inhibitors are a wonderful step forward for the treatment of our patients with type 2 diabetes. With this new class of medications, we can prevent cardiovascular death and preserve life. We can also reduce the risk for heart failure in these patients. SGLT2 inhibitors also appear to prevent kidney disease and preserve kidney functions.

These wonderful effects are the reasons I believe we should prescribe these medications. Patients with type 2 diabetes are at risk for premature cardiovascular death and heart failure. They also have a very high risk for kidney disease.

What About the Adverse Effects?

Because of the adverse effects of SGLT2 inhibitors, however, we are receiving a lot of mixed messages about using them. The adverse effect that is always mentioned is diabetic ketoacidosis (DKA).[1,2] In my opinion, DKA is not a major problem with these drugs.

We understand very well why DKA develops in patients treated with SGLT2 inhibitors for type 2 diabetes. These are patients who are insulin deficient; they do not produce enough insulin by themselves and are usually treated with insulin.

When these patients have a health event—a surgical procedure, myocardial infarction, or infection—they should be taken off the drug because they run the risk of developing DKA in these situations because of insulin deficiency.

How do these medications lead to DKA? The SGLT2 inhibitor improves insulin secretion, but patients then have less absolute insulin in the circulation. They then produce free fatty acids and ketones. Because of the mode and mechanism of action, ketones are generated just by giving the drug to these patients.

In most cases, this is good for patients. However, if they run out of insulin, they may then develop ketoacidosis. In those cases, you must make sure that you are giving your patients enough insulin if they are on an SGLT2 inhibitor plus insulin.

Fournier Gangrene

Infections also contribute to the mixed messages about using these agents. We know that SGLT2 inhibitors are associated with a slightly increased risk for genitourinary infections.[3,4] Usually, these are treatable, and once treated, the drug can be restarted.

There are also reports of a handful of cases of severe Fournier gangrene.[5] Of course, it is bad for even a single patient to have Fournier gangrene; however, among the many patients who are now treated with SGLT2 inhibitors, very few develop such side effects as Fournier gangrene.

For the Good of Your Patients

I am more worried that we won't start our patients on SGLT2 inhibitors because of these mixed messages. Dear colleagues, please consider using SGLT2 inhibitors in your patients in the future.

SGLT2 inhibitors prevent the risks for premature death and heart failure. They also appear to prevent kidney disease. Do not let these mixed messages about potential adverse effects stop you from treating your patients.

Be vigilant about these potential effects, but continue to use these medications for the good of your patients. I am pretty sure that you and your patients will be very happy because SGLT2 inhibitors also improve quality of life. Patients usually want to start them again after they have been discontinued for a few days—because of an infection, for example. Be vigilant in terms of the adverse effects, but do not let them guide your prescription of these drugs.

Thank you very much.

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