COMMENTARY

Insulin Updates From EASD 2020

Anne L. Peters, MD

Disclosures

October 05, 2020

This transcript has been edited for clarity.

Here are some updates from the EASD 2020 meeting, which was our second major diabetes meeting held virtually. It was supposed to be in Vienna. I wish we'd been there but, of course, we weren't.

I'm going to talk about insulin because, frankly, it's something that's very important to my patients. Many of my patients want faster-acting insulin because they have continuous glucose monitors and they see that insulin lasts too long and starts acting too slowly.

Ultra Rapid–Acting Insulin Lispro

New phase 3 data were presented for Lilly's new ultra rapid–acting insulin lispro. This insulin has been approved for use in the United States in patients on multiple daily injections, but not in those who are on insulin pumps. This was a 16-week study that enrolled 432 patients with type 1 diabetes on pumps. The primary outcome was change in A1c.

When they compared the ultra rapid–acting insulin lispro with standard lispro, they showed no difference in terms of A1c reduction. The A1c reduction with the ultra fast–acting insulin was 0.7% compared with 1% with the standard insulin lispro. There was also no difference in time in range.

When they did the standardized mixed-meal tolerance test, they found a reduction in 1- and 2-hour postprandial glucose levels with the ultra rapid–acting insulin. Those on the ultra rapid–acting insulin also spent significantly less time in hypoglycemia.

As for adverse events, the ultra rapid–acting insulin was associated with a higher rate of insulin pump site–related adverse events: 60.5% vs 44.7%. Rates of severe hypoglycemia and diabetic ketoacidosis did not differ.

I'm a little bit concerned about this difference in infusion-site adverse events because infusion-site issues can be a big issue for my patients on insulin pumps. I really want to understand whether this is something that is specific to this ultra rapid–acting insulin or whether it was just an anomaly of this study.

This insulin is approved for insulin pump use in other countries, so I think we'll [learn from their] experience as well. It's important when using a new insulin in a pump to make sure that patients are well educated about pump troubleshooting and know what to do if there's an infusion site–related issue.

Ultra Rapid–Acting AT247

There was an even more ultra rapid–acting insulin presented: Arecor's study with AT247. There's not even a name for this compound yet.

This was a phase 1 study. They took 19 men with type 1 diabetes and a really good baseline A1c of 7.1%. Each participant received a single dose of one of three things in a crossover design: AT247, insulin aspart, or faster-acting insulin aspart.

This was a euglycemic clamp study, so they looked at onset, duration of action, and how well each of these three compounds worked. They showed that AT247 was faster in terms of its onset compared with the routine aspart. It worked 23 minutes faster than the routine aspart and 9 minutes faster than the fast-acting insulin aspart. They showed that the glucose-lowering effect in the first hour or so after dosing was greater for AT247.

They also showed that the offset of insulin exposure, when it wore off, was significantly faster — about 20 minutes faster compared with both types of insulin aspart. Maybe this is a faster-on, faster-off insulin that would be better for use in hybrid closed-loop pump systems and even multiple daily injections. We need phase 2 and phase 3 trials to tell us whether this is clinically significant.

Once-Weekly Icodec

Finally, there's icodec, the once-weekly insulin. The full article was published in The New England Journal of Medicine. [This was] a phase 2, 26-week randomized controlled trial where they took 247 patients with type 2 diabetes and an average A1c of 8.1%, and gave them either once-daily glargine or once-weekly icodec. The primary endpoint was change in A1c.

There was no significant difference between the two groups. There was a 1.33% reduction in the icodec group compared with a reduction of 1.15% in the glargine group. In both groups, the patients' A1c levels were less than 7% at the end of the study. These patients did great in both groups, and it just shows you the benefit of having a study coordinator and a clinical trial for getting patients to uptitrate their basal insulin.

There were low rates of hypoglycemia, but — and this is a new concept to me — the insulin icodec was started at a dose of 70 units once a week. To me, that seems like a huge dose. They started the patients on their daily glargine at 10 units per day, so that's 70 units a week. The whole point of this is that it gives you a big dose once a week. They adjusted the doses of the insulin weekly.

The ultimate icodec dose, if you look at it per day, was 33 units per day vs glargine at 41 units per day. This begs the question, of course, of whether this could be mixed with semaglutide, where you give somebody a once-weekly GLP-1 receptor agonist and a once-weekly insulin.

I find this intriguing, but it makes me a little bit nervous because what if I give once-a-week insulin and then I have to change the insulin dose? What if someone's going in for surgery? What if somebody develops hypoglycemia? What if somebody starts exercising? There are so many [instances] I can think of where I might need to adjust an insulin dose more often than once a week.

Clinically, I need to be shown that this is really safe, and I want to see phase 3 trial data. However, I do find these phase 2 trial data intriguing.

Just last week when I was discussing giving once-weekly semaglutide, a patient said to me, "Weren't you the doctor who once worried about a once-weekly GLP-1 receptor agonist? And didn't you tell me that I should be on once-daily liraglutide because it was easier to adjust?"

I thought, Yeah, that was me. I realized that I've changed regarding a once-weekly GLP-1 receptor agonist because I feel safe with it, and I actually see the benefits of a once-weekly drug.

Again, I need to be shown that this is going to be safe and effective in a once-weekly way, but I want my skepticism to be proven wrong because I do think it's easier for patients to do something once a week rather than once a day.

Those are my insulin updates from EASD. This has been Dr Anne Peters for Medscape.

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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