Selecting and Using a GLP-1 Agonist in T2D

Variables that affect clinicians’ selection of and prescribing patterns with GLP-1 agonists in type 2 diabetes.

Troy Trygstad, PharmD, MBA, PhD: Let’s go back to the scenario in which I’m a patient who just walked into your clinic. I’ve got a history of cardiovascular complications. You’ve now considered GLP-1 [glucagon-like peptide-1], except I have a stop that says, “I can’t.” What are the stops?

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Sure. There are a few. As we talked about earlier, in terms of an adverse-event profile, it’s pretty tolerable. The biggest one is the GI [gastrointestinal adverse] effects, and again, that can be minimized through some of the things that we talked about. Pancreatitis—so prior history of that would be a hard stop, when you wouldn’t want to put that patient on it. There are very rare forms of cancer. You’ll see some warnings regarding thyroid cancer, specifically medullary thyroid carcinoma and multiple endocrine neoplasia type 2. But again, they’re very rare. Most of them have been seen in both genders of rats and mice. It hasn’t translated to human expression, but those are the ones where you wouldn’t want to roll the dice there.

Troy Trygstad, PharmD, MBA, PhD: So GI distress, thyroid, pancreas, and some rare forms of cancer. History of those. Not necessarily a hard stop on the GI, but it’s a hard stop on the others. But definitely counseling on GI is warranted. If they have irritable bowel syndrome or something like that, is that also a stop?

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: I’ll take a step back and kind of explain why those are my hard stops, and I’m curious to see what other folks are doing. The pancreatitis is one, and then the thyroid cancer is one. Now, if you have thyroid disease, because we get that question a lot, if a patient is being managed… I’m practicing under a scope at our institution. I have a supervising physician who gives me blanket powers to prescribe any medication that I deem necessary. So I wouldn’t want to take unnecessary risk on their license, so to speak. And so I have other endocrinologists whom I will kick the case to, and they’re like, “Oh, well, this person had a bout of pancreatitis, but it was for X, Y, and Z reasons. I’m willing to roll the dice and have this patient on it.” So those are my hard stops, because of the format that we’re prescribing and practicing in. But yeah, those are probably the 2 main ones that come to my mind.

Troy Trygstad, PharmD, MBA, PhD: So really what you’re saying is that there’s the conventional case, and you’re feeling good about that. When there’s an unconventional case, it may or may not be a hard stop, but you’re kicking it to the endocrinologist at that point.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: I’m just trying to say, “There’s really nothing else I could do for this patient. I’m thinking of rechallenging it. Are you comfortable with me doing this?” And that’s when I would kind of just quickly curbside them.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: I would agree with that. And I think in terms of irritable bowel, that wouldn’t be a hard stop for me. Gastroparesis would be. And so if you have a patient with gastroparesis, that’s where, again—if you think about the mechanism of action—the fact that we’re slowing down the GI tract, well, that’s what gastroparesis is. And that’s the reason why we see the hypoglycemias, which, again, we talked about as very serious. So we want to avoid that at all costs. So in this particular case, if there was gastroparesis involved, that would be a hard stop for me.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Absolutely.

Jessica L. Kerr, PharmD, CDE: And I think I probably extend medullary thyroid cancers out to family—primary relatives on that one. Pancreatitis—I’m really just looking at the patient, themselves. When I do look at the pancreatitis risk, I also look at where their triglycerides are. A lot of our patients may consume alcohol, which could be a risk factor for pancreatitis or just their triglycerides in general. A level already puts them at increased risk for pancreatitis. We know patients with diabetes are at higher risk for pancreatitis, and then we just weigh in that the radical mechanism of the GLP-1s could increase with the proliferation of the cells and those types of things.

Troy Trygstad, PharmD, MBA, PhD: With the GLP-1 agonists, we have some considerations, clearly, but back to the benefits, then, we’ve got lower A1C [glycated hemoglobin].

Jessica L. Kerr, PharmD, CDE: Lower A1C.

Troy Trygstad, PharmD, MBA, PhD: Maybe better time in range. I love that term.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Cardiovascular data.

Troy Trygstad, PharmD, MBA, PhD: Maybe some weight loss, maybe some cardiovascular benefit. Anything else?

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Some early renal data. They’re looking at them now from a renal standpoint. Similar to the benefit they are getting from an ACE [angiotensin-converting enzyme inhibitor] or an ARB [angiotensin receptor blocker], you’re seeing them. They weren’t done in a dedicated trial, but some of the ongoing ones are looking at some renal end points.

Troy Trygstad, PharmD, MBA, PhD: Anything else around the corner?

Susan Cornell, PharmD, CDE, FAPhA, FAADE: Low-risk hypoglycemia.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: That’s a big one.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: Again, I think that’s the biggest thing. Because again, that is what’s causing most of the problems, especially the cardiovascular risk. When you’re dropping low, you’re putting your body into shock, and of course, that’s where we often see death—from the hypoglycemia. So that low-hypoglycemic risk with weight loss, cardiovascular safety, potential renal safety, and better time in range makes it a good class.

Troy Trygstad, PharmD, MBA, PhD: So better time in range. A little bit like the way we think about sun and skin cancer now is that a burn is a burn. You are too far out of range, and that’s going to have some effect over time. But if you’re relatively within range, and you are putting on sunscreen regularly, then you’re probably in a much better position. Out of range.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: Yeah, and it leads to prevention. You brought up prevention because, again, now we know sunscreen will prevent this. So we’ve created a culture to prevent. We need to do the same with diabetes. We need to create a culture to prevent. I know we talked about guidelines, and most folks who know me know that I’m a big fan of GLP-1s, and even SGLT2 [sodium-glucose cotransporter 2] inhibitors. But why is metformin still a first-line treatment option? Where metformin fixes 1 broken organ, GLP-1s fix 6. From a preventive nature, which really has the better data? And so, again, if we can prevent it, which if we look at prediabetes, GLP-1s are 1 of the recommended treatment options. So is metformin, but again, it’s a recommended treatment option. So again, why are we waiting until there’s a problem and then trying to put a bandage on a hemorrhage? Let’s just prevent it from happening.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Because if given the option, if money was no object, you could pick. And this happened for my dad, who has type 2 diabetes. I had him on metformin, an SGLT2 inhibitor, and now he’s on a GLP. I said to take one off, and most would probably not think about taking the metformin off. But knowing what the data are, it’s the weakest out of those 3 classes that we talked about. But I don’t think it’s going to change from a guideline standpoint, because when you think about it from a population health standpoint, it’s a $4 drug.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: Or less.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Or less. In some cases, they give it to you for free. It’s tolerable, with very minimal adverse effects. So I think it’s a great first-line agent, but if you put it to the same rigor that these drugs went through, from a cardiovascular safety standpoint, I don’t know that it would pan out. But overall, just from a population health standpoint, I don’t think either guideline is going to make that change anytime soon.