COMMENTARY

SGLT2 Inhibitors in T1D: 'People Are Using Them Now'

Anne L. Peters, MD

Disclosures

March 30, 2021

This transcript has been edited for clarity.

At the Endocrine Society meeting, I had the privilege of debating Dr Andy Ahmann about whether people with type 1 diabetes should be taking SGLT2 inhibitors. Now, this is actually something I've done for a long time off-label because I know it helps some of my patients with type 1 diabetes achieve better glycemic control. But I've also been very involved with discussions about the risk for diabetic ketoacidosis (DKA).

I was asked to present the con side of using SGLT2 inhibitors in people with type 1 diabetes, and Andy talked about why we should [use them]. I'm going to give Andy's side first.

Reduce Unpredictability, Variability, and Distress

Basically, the reason to use SGLT2 inhibitors in people with type 1 diabetes is that they help patients achieve better glycemic control. But it's not that their A1c goes from 8 to 6. What I see and what my patients have told me is that it helps reduce some of the unpredictability and variability in their numbers, which helps reduce their diabetes distress and makes them feel like it's somewhat easier to manage their diabetes. You do, on average, see an A1c reduction in the range of 0.3%-0.6%. You also see some weight loss, although it's not much; it may be on the order of 1-3 kg. Obviously, there is a patient-driven desire to use these agents because it makes them feel better and it helps them manage their diabetes.

Andy talked about the real, overarching reasons to use these agents, and they really have to do with their nonglycemic effects. We know that SGLT2 inhibitors in type 2 diabetes and in people without diabetes have a marked benefit in terms of renal dysfunction. They help patients with proteinuria slow down their progression to end-stage renal disease. We also know that these agents are very helpful in people with heart failure and help prevent hospitalizations for heart failure.

He would argue that you should use these agents in people with type 1 diabetes who have those high-risk characteristics. Frankly, if I have a patient with type 1 diabetes who has proteinuria and who is actively working with me to manage their disease, adding an SGLT2 inhibitor makes sense in terms of helping them slow progression of their nephropathy.

Risk for DKA Can't Be Eliminated

My side of the argument is that I can't eliminate the risk of patients developing DKA on these agents. In every one of the clinical trials, there was an increased risk for DKA when treated with an SGLT2 inhibitor in people with type 1 diabetes compared with those in the control group. These drugs do increase the risk for DKA.

In Diabetes Spectrum, we recently published a list of the different protocols used to help reduce the risk in our patients, but none of these protocols have been studied in a systematic way. In the clinical trials of SGLT2 inhibitors in people with type 1 diabetes, efforts to help mitigate this risk were variable and didn't seem to me to really do the right thing. They didn't provide enough patient education or enough practice doing ketone testing. There's a lot that I think we have to do in order to choose the right patients.

Moreover, I am very worried that if these drugs are approved for use in type 1 diabetes, the wrong patients will be started on them, meaning the patients who are doing the worst, who aren't taking enough insulin, and who may be ketotic at baseline.

The use of these agents really needs to be reserved for patients who are testing their sugars, who are not ketotic at baseline, and who have an A1c that is at least reasonably controlled; I use a cutoff of 9%. I really want a patient who is working with me who I know can be taught to test their ketones if needed.

Also, patients must have access to medical care because they can develop euglycemic DKA, which is DKA with relatively normal glucose levels. The way to get rid of the DKA — the ketones — is to have the patient take more insulin. Often, glucose levels aren't terribly high in these individuals, so I have them consume carbohydrates so they can take more insulin and get rid of the ketones. Obviously, I have them consume fluids to get rid of the dehydration. I really need patients who I work with closely in order to feel safe using these agents, particularly because they're being used off-label.

FDA Approval Will Mean More Regulation

In the end, I think Andy and I agree. We agree that there's a benefit for our patients with type 1 diabetes — to some degree a glycemic benefit, perhaps more in terms of effects on nephropathy and heart failure. These studies need to be done or we'll just have to extrapolate from studies in people with type 2 diabetes and in those without diabetes.

I think we both agree that you can't completely eliminate the risks. It would be nice if some sort of protocol were studied in a prospective way to see how much risk reduction we can see.

Hopefully, at some point, the FDA will feel comfortable approving these agents, in part because of the benefits I've discussed, but also because if the FDA approves it, then there's going to be more regulation. There will be more education, and maybe it can be coupled with prescriptions from the pharmacy for ketone test strips.

I don't know exactly what kind of monitoring we'd do if these drugs become available for people with type 1 diabetes. I would hope that by approving this class of drugs for people with type 1 diabetes, we'll be able to make them even safer to use. Frankly, people are using them now, so why not make it something that's allowable and try to use them as safely as possible?

This has been Dr Anne Peters for Medscape. Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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