GLP-1 Agonists in T2D: Response to Therapy


Characteristics that affect a patient’s response to therapy with a GLP-1 agonist in type 2 diabetes.

Troy Trygstad, PharmD, MBA, PhD: So this sounds like the conversation from earlier in which guidelines, as we think of guidelines, are starting to bleed over into other conditions. It used to be that we would silo out this condition or that condition and everything was in the vacuum of that condition. Even the trials were for patients who may not have a lot of comorbidities. But the reality is that most of our patients have plenty of comorbidities, and what you choose for diabetes may be impacted more by some of the other things that are going on with the patient, just as much or maybe more than what’s going on with their diabetes.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: And I think we need to take the patient into consideration because the other thing is the delivery, or the administration. Dhiren brought up Tanzeum, or albiglutide. Well, 1 of the challenges was the delivery of the drug. So if we look at the pen device and its user-friendly nature, that is actually what’s taking over the marketplace right now. If I have a medication to give to my patient and the patient can’t figure out how to use it or use it correctly, what good is that drug? So if we look at something as simple, from a clinical standpoint, as liraglutide versus dulaglutide, the needle delivery is very different. And we need to spend the time teaching the patient proper technique, especially if I have to switch between the 2 because, again, what’s in my refrigerator? It makes a big difference.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: And the other point that I’ll add is that in addition to A1C [glycated hemoglobin] as a big factor, the other one is weight. They’re not all created equal, from a weight standpoint. In some of the newer trials that we have, we have head-to-head studies, again with another once-weekly GLP-1 [glucagon-like peptide-1], where you might be seeing twice the weight loss for the same or equivalent A1C reduction, right? And so if you’re going in with the mind-set that this patient needs further weight reduction, I might lean toward 1 over the other, in addition to the glycemic benefit.

Jessica L. Kerr, PharmD: And even hitting on that topic of the weight loss, I think so many people in this society want that magic pill for their weight loss. I think it’s very important for us to educate them and let them know that you may see a 2- to 10-pound weight loss. I will also say that I’ve had patients who have lost 30 pounds. Was it the medicine? No. I think it was Hawthorne effect. They saw the benefit that it was providing, so they started to get their lifestyle a little bit on the ultra-side, to have those results. But there’s also about 30% of patients who don’t lose any weight. So it’s about making sure that you’re not setting them up for disappointment. But the biggest thing is that it is at least neutral compared with older generations or different classes of drugs.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: Yeah, and I would agree. We run our obesity medicine clinic out of our endocrine clinic, and I can tell you that we use GLPs for weight loss quite a bit. And what I would love to be able to figure out are my responders versus nonresponders. I have a preset patient profile that I’m seeing for the most part, and I have some who just do really well. Last week we had 2 patients on higher doses losing 60 pounds over the course of a year. I mean, we’re seeing some really good results with it. But again, at the same time I’m thinking, “All right, I think I have this figured out.” And I put the next person on it, and their case is not the same. So again, these are things to factor in, but a lot of those conversations that I’ve had are like, “I was in a diabetes support group. My friend went on this and lost this amount of weight. I want to go on it.” And I tell them, “Yes, it has a weight-loss profile, but I can’t guarantee that you’re going to lose 20, 30 pounds because your friend lost 20, 30 pounds.” So I think just setting those expectations early on makes a big difference.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: I think the 1 thing we all hear from patients who do start on a GLP-1 is how much better they feel afterward.

Troy Trygstad, PharmD, MBA, PhD: Correct.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: They feel full for the first time in who knows how long, and it goes back to, once again, that mechanism of action and that satiety factor. But I can say, for the most part, every patient who tries a GLP-1—or most, I should say—is very pleased with how they feel afterward, if they can get through the nausea and the vomiting, which, again, is individualized with slow titration or an appropriate titration. But as you put it, Dhiren, these are the patients who come in and hug you afterward because they feel so good.

Troy Trygstad, PharmD, MBA, PhD: But in that context, it almost sounds to me as if what you’re arguing for is that it’s a behavioral modification aid in some ways.

Susan Cornell, PharmD, CDE, FAPhA, FAADE: Exactly.

Troy Trygstad, PharmD, MBA, PhD: And that we have some therapies out there that we’re familiar with that are sort of helping the body realize or are creating a feedback loop that sort of says, “Hey, heads-up, I’m giving you the proper feedback to your brain that should be happening when there’s an absence of that positive or negative feedback loop.” And this might have that affect for slowing down eating, or reducing overeating, and that’s significant because now we’re not just talking about, again, diabetes and cardiovascular. We’re talking about psychology. We’re talking about behavior modification.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: It amplifies that behavior change. And if you think about it, you’re spot on. You think about where we came from before these 2 new classes came. We were always putting those folks on drugs: SUs [sulfonylureas], TZDs [thiazolidinediones]. They’re all going to gain weight. So for the first time, they were being put on a class of medications for which they’re pulling in the right direction for what you’re telling them to do. It’s the first time the diet is clicking, along with the exercise, along with the medication. You have not had that trifecta for a long time.

Troy Trygstad, PharmD, MBA, PhD: So you went from, “Here’s why this is good, but,” to “Here’s why this is good. Oh, by the way, you’re going to lose weight, so you really need to hop on that treadmill.”

Susan Cornell, PharmD, CDE, FAPhA, FAADE: If we think about it, the majority of the drugs that are made to treat diabetes, these newer agents, really simulate a lifestyle modification. And when teaching patients, I always say, “You know, you can’t look at the drug as if it is going to fix this for you. The drug is always an adjunct to lifestyle. You need to make the lifestyle changes. The drug will help you to do that.” But if we look at the medications, metformin is nothing more than eating breakfast. It does the exact same thing as if you eat breakfast. Metformin is the same mechanism of action. GLP-1s are small frequent meals. That’s what it comes down to. So it’s really portion size and control of the food you have. Now, we can’t say that people are choosing healthy choices, but we’re hoping that they do. And maybe that’s the differential, Dhiren, of what you’re seeing—of the responders versus nonresponders. Healthy choices and maybe not so healthy.

Troy Trygstad, PharmD, MBA, PhD: We mentioned the magic word early on in the discussions. It’s a hormonal circumstance. And we use hormones to do what? Messaging, right? So we’re getting into this space in diabetes of messaging versus that direction action type of a way of handling things. And really, what we’re trying to do is get the appropriate messaging in the body so that we have a normal homeostasis, correct?

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: And we’ve shown that at our institution. We’ve actually looked at people and looked at functional MRIs, and their response to GLPs. We’ve done a lot of early-on studies looking…. This one happened to be with both doses of liraglutide. But that feeling of fullness that you described is real. Patients will come in and tell us that, “Normally, I used to eat an entire steak and cheese, but now I can’t get through that. I eat only half of it.” So it’s working on your brain. It’s working on your gut. It’s working on your pancreas. Again, back to that mechanism of action, it’s that multimodal benefit, which you really don’t see with most other classes.

SGLT2s [sodium-glucose cotransporters 2] are great. We’re fans of them. But at the end of the day, they are working on [only] 1 of the organs that we described earlier. Out of the 8, it’s working [only] on the kidneys. So if I had to pick, I’m going to pick something that’s going to hit 5 or 6 of them. But there [are] going to be certain situations [in which] I’m going to obviously lean toward that. But if you had to pick 1, you have 1 that’s going to work on more.

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