SGLT2 inhibitors in Type 1 Diabetes: What Are the Risks?

Prof Simon Heller, BA, MB, Bchir, DM, FRCP.


March 12, 2019

My name is Simon Heller. I'm professor of clinical diabetes at the University of Sheffield in the north of England and I'm going to discuss the recent approval [EU positive opinion for type 1 diabetes] of one of the newer agents used in the treatment of type 2 diabetes, the SGLT2 inhibitors.*

A number of these drugs, for example dapagliflozin (Forxiga/Farxiga/Edistride, AstraZeneca), will soon be approved for use in certain people with type 1 diabetes. These drugs are already approved for the treatment of type 2 and they've been really quite useful. They help to lower blood glucose and improve HbA1c levels. They can also reduce weight, and perhaps most interesting of all, there's some evidence that they may reduce cardiac mortality. Perhaps, and this is speculation, but there is evidence that it might be because they have effects on reducing heart failure which is an issue in type 2 diabetes.

I think perhaps most interesting of all there's a suggestion that they may have benefits on the kidney, they may be what we call renoprotective, and we need to know more about that. But clearly if there were medications which prevented the complication of diabetic kidney disease, that would be fantastic.

So why not use them in type 1 diabetes? The reason that there has been caution and a bit of concern is that they do, in some cases even in type 2 diabetes, cause diabetic ketoacidosis, which is a potentially lethal complication.

And therefore, we need to be absolutely sure that they can be used safely.

So one of the issues is that they lower glucose levels by increasing secretion of glucose in the kidney, and therefore they may require insulin levels themselves to be reduced in people who are receiving insulin treatment. And could it be that that reduction in insulin is contributing [to ketoacidosis]? I think it probably is.

So is it a wise decision to allow these drugs to be used in type 1 diabetes? They clearly have potential benefits, and some patients think they're really great when they go on them. So in terms of quality of life … that's an issue. But of course, if they do increase the risk of ketoacidosis, which is potentially fatal, I think we have to be very cautious.

So, I think the approval has suggested that patients should be well aware of what needs to be done. And actually we've been involved in some of the clinical trials. And we have given patients very careful instruction about checking for their ketone levels, particularly if they're not feeling well, or that glucose has crept up.

But interestingly, even with all that advice, we have had a few patients who still got into mild ketoacidosis.

So I think we should regard this [upcoming] approval with a bit of concern.

I think if you have people with [type 1] diabetes, who are very well educated, know exactly what to do, and do everything that their doctor and nurse tells them, probably that's fine.

But of course, many individuals …find that challenging to do. There are people who don't take their insulin regularly who are at risk of ketoacidosis, whose HbA1c levels are often high. And if you're going to choose those people it could increase the risk that people might get very ill, or even might die, and that is my concern.

The other issue is that [SGLT2 inhibitors] are used widely by primary care physicians and in type 2 diabetes, that's generally very safe. But of course, there are people with type 1 diabetes who attend primary care clinics because they don't find it easy or rewarding to go to secondary care units where most type 1 diabetes is treated, at least in the UK.

I think giving these medications to people with type 1 diabetes without careful surveillance and expert supervision does increase the risk.

So I think it's likely …the use of these medications in type 1 will increase. But I think we should have some concerns and scrutinise the results, particularly those who have side effects, very carefully as we move into a new era.

* A second medication, the oral SGLT1/2 inhibitor sotagliflozin (Sanofi) has also recently been given an EU positive opinion , also for use in certain patients with type 1 diabetes, under strict criteria. Sotagliflozin is not approved for type 2 diabetes, however.


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