ADA 2025: Progress in Managing Type 1 Diabetes

Medscape

4 days ago

This transcript has been edited for clarity.
The one study that my patients with type 1 diabetes asked me about from the American Diabetes Association meetings was the Vertex study, where stem cell-derived islet cells were given to individuals with type 1 diabetes and followed for a year. They reported on 12 participants, and basically, these little islet cells worked.
The problem, of course — and the reason I had to disappoint my patients — is that it didn't work without immunosuppression. These patients required immunosuppression, but in the setting of immunosuppression, the little new islet cells worked.
We saw an increase in C-peptide production. Most patients got off of insulin. The patients had no further episodes of severe hypoglycemia, and the patients really were cured, in essence, of their type 1 diabetes — at least the small number of people followed for a year. The downside, of course, is the immunosuppression, and that's where the side effects occurred.
I think this was really interesting because it's certainly proof of concept that we can take stem cells, make islet cells, and infuse them into people and have them work. We just have to figure out a way to do it without immunosuppression.
The next study that my patients and I found interesting came from the Barbara Davis Center and was done by Dr Halis Akturk and his colleagues. It was looking at the use of semaglutide 1 mg as an adjunct to insulin in people with type 1 diabetes and obesity who are on automated insulin delivery systems.
Now, in full disclosure, I do this all the time in my patients who are overweight or obese who wish to try combination therapy off-label with semaglutide, but this is the first randomized controlled trial to show the benefit.
This was called the ADJUST-T1D trial. It was a double-blind study. This was a 26-week placebo-controlled study, and they enrolled 72 individuals with type 1 diabetes from four US clinics. They were randomized 1:1 to semaglutide or placebo once weekly while they continued on their usual automated insulin delivery systems.
The insulin adjustments were guided by the investigators, along with the patients, looking at time in range, time below range, and other continuous glucose monitoring parameters. These individuals had to have a BMI ≥ 30 and an A1c between 7% and 10% coming into the study. These are fairly typical individuals with type 1 diabetes who are overweight, and they had a baseline A1c of 7.7%.
The primary outcome was a composite one, looking at how many people achieved a time in range of > 70%, time below range of < 4%, and ≥ 5% weight loss. This composite endpoint was met in 36% of the participants in the semaglutide group, and this was highly significant compared to the placebo group.
In terms of secondary outcomes, there was a reduction in A1c by 0.7% in the semaglutide group compared to 0.3% in the placebo group. Time in range improved. People lost, on average, 18 lb, and there was a reduction in total daily insulin dose. There was no diabetic ketoacidosis, but there were two episodes of severe hypoglycemia in each group.
This was really proof of concept, which I think all of us who treat many people with type 1 diabetes and have been using incretin therapy have shown to be beneficial. I think the things we still need to watch for is obviously weight loss that's too fast because I don't think this is good for anybody, and the fact that people will need less insulin, so the insulin doses need to be reduced as people use these agents.
Patients on these automated insulin delivery systems tend to do pretty well. I'm often adjusting the carb ratio and maybe the sensitivity depending on the pump, but I found this to be a pretty safe and effective way to do it. I think you just start lower, you go up slowly, and you make sure patients are tolerating the medication. I think patients really see benefit.
What's not measured here are the nonglycemic benefits that we know are part of the use of incretin therapies, which I think is important. In my own clinic, I looked at outcomes at 2 years retrospectively, and people had still maintained the weight loss but some of the glycemic improvements waned over time.
I think that just goes to show the difficulty of managing people with type 1 diabetes. I think this helps, and I think this was a really good trial. I'm very grateful to the investigators for doing this study.
These two presentations highlight some of the progress in how we're thinking about dealing with type 1 diabetes. First, the notion of hopefully, someday having a cure that helps people with type 1 diabetes, having new beta cells that actually work. The second is using some of the drugs that we're now familiar with in terms of their benefits to people with type 2 diabetes in people with type 1 diabetes, and showing that it can be done safely and effectively.
This has been Dr Anne Peters for Medscape. Thank you.