Overview of GLP-1 Agonists

A highlight of the available agents and the differences among them.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: There are a lot of options that we have, not only within the diabetes medications. There are 12 or 13 different classes of them, but there’s also a variety of different medications within a given class. And a GLP-1 [glucagon-like peptide-1] receptor agonist is 1 good example of that. We have 6 to 7 agents that are in that class, and it’s important to recognize what some of those differences might be. We have medications that are injected twice a day, such as the original exenatide, which is Byetta, and medications that we have on the other end that are once weekly, such as semaglutide or Ozempic.

And so we have about 3 of them that fall into that once-weekly category. So I mentioned Ozempic, which has the generic name semaglutide. We also have Trulicity, which is dulaglutide. We have Bydureon, and that comes as the auto-injector as well as by itself. And those are all of our once weeklies. We used to have, on the market, albiglutide, which is Tanzeum, but that’s no longer the case, and it has been discontinued. Then we have our once daily, which is liraglutide. The brand name on that is Victoza. And then, as I had mentioned earlier, we also have our twice-a-day medications, and then an additional one that we have that’s still a once a day is lixisenatide.

So again, we have the kind of continuum, and they’re not all created equal from an A1C [glycated hemoglobin] reduction standpoint. They’re not all created the same from a weight-loss standpoint, and where they’re also not created equal is from a cardiovascular data standpoint. So of the ones that we’ve just listed, the majority of them are what we call cardiovascular neutral. They don’t increase a patient’s cardiovascular harm, nor do they confer protective benefit. The 2 exceptions to that are liraglutide and semaglutide. And that piece of information is going to continue to change. We know there are some others in the pipeline. We haven’t had the full results. We’re going to get them at this ADA [American Diabetes Association Scientific Sessions] meeting in 2019, but that might change for other GLP-receptor agonists. But those are what I’d say are the major differences among those.

Tripp Logan, PharmD: When GLP-1s first came out, the dosing was pretty often—once a day or twice a day. And injections once a day or twice can be intrusive to a patient that is not used to administering an injection. Over time they became available in formulations that could be given weekly. Sometimes the mechanism and the administration technique was somewhat cumbersome, and we dealt with some of that and helped patients through that process.

Now with most of them being weekly dosing, that’s pretty agreeable to most patients to have a weekly injection and not having to carry a pen or a syringe with them every day. So that’s really positive.

These GLP-1s that are available now also have different risks and benefits, different out-of-pocket costs, different formulary status when you get the individual patients. So our approach is always access first. And so we see what out-of-pocket cost is, and is that a barrier to access? If the patient picks up the prescription for a $50 co-pay for a GLP-1, and they pick it up and smile and say thanks, but what they’re really saying is, “I’m never going to pick this $50 medicine up again,” that does them no good, and it does us no good. So we really work hard to ensure that whatever their out-of-pocket cost is, it’s not a barrier to access.

And then once we do that, then we try to customize what this therapy is for this patient. Most of the time formularies dictate what that is, and out-of-pocket does as well. But some of the GLP-1s now have shown to have some cardiovascular benefit. Well, with patients with cardiovascular disease or a superhigh risk of cardiovascular disease, that’s a consideration that we could take with these products, for sure.

Also, when we’re looking at all these GLP-1s as a whole, there are a couple more that there are trials going on now to see if they have cardiovascular benefits as well. And just knowing how these drugs work, the cardiovascular benefit makes sense, and it’s something that definitely should be considered when prescribing, knowing that once that prescription is prescribed, oftentimes it’s not on formulary and that patient has to have it changed to something else. But cardiovascular benefit is really important. Weight loss is something else that is important, not only to patients but just to get their glycemic control with a patient’s care plan.

When a prescriber initiates somebody on insulin, 1 of the conversations we always have is that there’s a potential that you could have some weight gain with this. That’s another benefit of the GLP-1s, that you don’t have to have that conversation; the conversation is much more appealing. You could potentially have weight loss with this medication as well. So that’s a selling point, so to speak, with patients when we’re onboarding and we’re talking to them about administration and how to get going on this new product today, that they’re getting this new medication. Weight loss is definitely a selling point for that.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: My personal experience with GLP-1 receptor agonists has been excellent. Most patients tolerate it very well. They see some great weight loss with it. In addition, the reasons that we put the patients on these medications is to improve their glycemic control. I always joke around. I usually get my hugs from those who are on the GLP-1 receptor agonists. They have been uncontrolled for a really long time. They might have been used to being on medications that cause weight gain. Now, for the first time, they have a medication that’s helping them lose weight and helping them with their blood sugars, among many other things that they do, to just making sure. There might be some protective kidney benefit that we’re seeing early on from some of these clinical trials. So there’s a variety of different things as to why patients like it, including ease of use. And the biggest one that I didn’t mention earlier is the hypoglycemia piece, and it has a very low hypoglycemia risk profile compared with sulfonylureas, TZDs [thiazolidinediones], or insulin for that matter.