John R. Petrie, MD, PhD

Disclosures

October 20, 2017

Hi. I am John Petrie, here in Lisbon at the 2017 European Association for the Study of Diabetes (EASD) meeting. I am here to talk about findings of the DEPICT-1 study that are being presented at the meeting.

Using sodium-glucose cotransporter-2 (SGLT2) inhibitors in type 1 diabetes is a strategy to help people with type 1 diabetes get better control of their blood glucose. Glucose drives cardiovascular (CV) disease in type 1 diabetes, and controlling glucose is very hard for many people. The idea of taking the SGLT2 inhibitors from type 2 diabetes and using them in type 1 diabetes is being pursued by at least two companies presenting here at EASD.

DEPICT-1 evaluated adults about 43 years of age with type 1 diabetes randomized to 5 mg dapagliflozin, 10 mg dapagliflozin, or placebo [all as an adjunct to insulin]. The primary outcome was A1c reduction; researchers also looked at weight and blood pressure. Most important, the study looked at adverse events.

SLGT2 inhibitor use in type 1 diabetes was forging ahead until about 2 years ago, when concern about increased risk for diabetic ketoacidosis (DKA) was raised by the diabetes community. Everybody is watching to see how many cases of DKA come through in these new trials.

The DEPICT-1 study showed a reduction in A1c of about 0.45% from baseline after a run-in period. It showed a reduction in weight by about 3 kg and a reduction in insulin dose that is really quite large—roughly 8 units a day.

There were very few excess cases of DKA with dapagliflozin in either dose, with the rates being about 1.2% for placebo and 1.7% for the top dose of dapagliflozin. This is helping dapagliflozin move toward getting an indication in type 1 diabetes. It is providing some safety data. There will be a 12-month follow-up, as well as a 6-month follow-up, which is what the study currently is.

In the diabetes community, we feel that the drugs could be licensed by the US Food and Drug Administration (FDA) for use in type 1 diabetes if they are found safe at 12 months. Longer-term studies of CV safety are important because there are no CV outcomes trials in type 1 diabetes.

Given that there are so many trials now in type 2 diabetes, we think that companies should look at this in type 1 too. The [CV] risk is just as high and there is no reason why people with type 1 diabetes should not also have CV outcomes trials to know about the safety potential and benefit of these drugs.

Dapagliflozin is one candidate going forward. Data on another candidate, sotagliflozin, was presented today in our symposium at EASD. The studies are very similar in many ways, although the dose of insulin reduction was slightly less with sotagliflozin, and the rates of DKA look a little bit higher than they do with dapagliflozin.

Some of this may be due to the way the study is designed and the mitigation strategy, because patients are being reviewed very frequently with monitoring of ketones. If this is going to be used in clinical practice, we need to have a trial that is more pragmatic, in which the standards of care are more like usual care at the study sites.

After these studies are completed, there is hope that SGLT2 inhibitors could get an indication for type 1 diabetes, offering a helpful strategy for people trying to get better glycemic control and reduce their risk for CV disease.

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