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GLP-1 Agonists for the Treatment of Type 2 Diabetes - Episode 11

Novel Strategies for T2D and Comorbid Conditions

Vanita Aroda, MD: What are some of the exciting areas in GLP-1 [glucagon-like peptide-1]? First of all, we have now seen the completion of a phase 3 program of an oral GLP-1, and that’s the first oral peptide in type 2 diabetes. This is oral semaglutide.

In addition, the phase 3 program for an implantable GLP-1 has been completed—that’s ITCA 650, an osmotic pump with exenatide. So that’s an implantable device with continuous delivery of the GLP-1.

We’re also starting to see some phase 2 data of twincretins. We are looking at the combination GLP-1 with GIP [glucose-dependent insulinotropic polypeptide]. And so there’s a lot of excitement to see what GLP-1 can do with other hormones in combination.

What I’d be interested in seeing are studies that look at earlier incorporation of GLP-1, compared with even earlier therapies, to see whether we can affect long-term outcomes—not just in those with established cardiovascular disease but in the overall population that we see on a day-to-day basis.

John B. Buse, MD, PhD: It been an exciting time in diabetes management, and the GLP-1 receptor agonists have provided a lot of benefits, as we’ve discussed—not only reducing cardiovascular risk but promoting weight loss. That said, there’s more to come. So there’s a product called ITCA 650, which is exenatide. It’s the same drug as the original GLP-1 receptor agonist, but instead of being a twice-a-day injection, it’s packed into what’s called a mini osmotic pump. It’s a titanium rod that has a very special membrane and a plunger that swells over time as tissue juice gets into the plunger. As the plunger swells, it squirts out exenatide at a constant rate. The long-term aim is to have this as a 6-month or even a 1-year implant, which I think would be a great thing for adherence. People would not have to remember to take a drug twice a day, or once a day, or once a week, but literally would be going to the doctor and having this rod put in through a very minor surgical procedure once every 6 months. That would be a game changer for many patients.

And then the other real excitement is there’s an oral formulation of the same drug, semaglutide, that’s available today and is being tested. It’s coformulated with something called SNAC. The capsule is swallowed with a small glass of water first thing in the morning. Probably the best thing is for people just to swallow the capsule with a swallow of water and go back to bed, or be still, because that SNAC enhances the absorption of the semaglutide, which is a protein, across the stomach lining. The early clinical trial reports, largely through press releases today, are incredibly promising. So this looks to be as effective an approach to glucose lowering and weight-loss promotion as the injected semaglutide once-a-week as a once-a-day capsule. And for the small proportion of patients who just can’t get over the idea of taking an injection, I think this will bring semaglutide to that additional segment of the population.

So I think those are the major near-term developments. There are a number of other GLP-1 receptor agonists that are being developed, and I’m sure there will be other approaches, including nasal delivery and other formulations that will come in the future.

I think the biggest challenge is getting patients with clinical cardiovascular disease on these drugs. Nearly a third of the population has clinical cardiovascular disease in the setting of type 2 diabetes, and the best evidence is that no more than 5% to 10% of them are using these very effective drugs.

John Anderson, MD: It’s never fun having type 2 diabetes. Let me just be clear about that. But in this day and age, we have so many tools at our disposal. We have so many better medications. We have several classes. We are now finding cardiovascular benefits in a diabetes medicine. If you had told experts that 25 years ago, they’d look at you like you were crazy. So we have these medications. We have to start using them routinely. We have to be advocates for our patients. And if that’s an injectable, then so be it. It’s an injectable. Let’s find the best agents for our patients. Let’s not shrink away with cost as the only defense when, in fact, a lot of these agents are affordable for a vast majority of our patients.

Transcript edited for clarity.