T2D Treatment Guidelines: GLP-1 Agonists

Recommendations for using GLP-1 agonists in the treatment of type 2 diabetes based on more recent ADA and AACE therapeutic guidelines, and expectations for managing patients as additional data emerge in the field.

Troy Trygstad, PharmD, MBA, PhD: So Dhiren mentioned guidelines, Jess. What should we know as of early 2019, which is now? What’s changed in the guidelines? What’s the CliffsNotes version of how the GLP-1 [glucagon-like peptide-1] agonists relate to guidelines?

Jessica L. Kerr, PharmD, CDE: There’s been a major shift in our guidelines when we’re looking at the ADA [American Diabetes Association] guidelines or the AACE [American Association of Clinical Endocrinologists] guidelines. We still have that background therapy with metformin as being that primary first-line agent, unless there’s a contraindication or intolerabilities to metformin. But really, what we’re seeing with the GLP-1s is after the patient is no longer controlled with metformin you can immediately jump in with the GLP-1 options. With that being said, if we have a patient who has cardiovascular concerns, or if we have a patient who has heart failure concerns, or if we’re trying to promote weight loss or limit hypoglycemia, these are all great agents that you could immediately go to after we’ve explored the metformin therapy, when you’re looking specifically at the guidelines.

Troy Trygstad, PharmD, MBA, PhD: So I’m still thinking metformin to start, but if that’s not working or I’ve got these ancillary special conditions or comorbidities, I might be looking straight toward these types of therapies.

Jessica L. Kerr, PharmD, CDE: Yes.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: At the end of last year, the new ADA guidelines came out. And we know from the ADA/EASD [European Association for the Study of Diabetes] consensus report, and I think in the AACE guidelines, that GLPs have been favored for a long time, which we all would agree with. Because some of the agents we’re going to talk about today have what we call cardiovascular outcomes data, and now the ADA, while a bit late but I think better late than never, said after your first-line of metformin, the question that you need to ask yourself as a clinician is, does the patient have established cardiovascular disease? And if so, they want you to use this group of drugs that have this data. And the GLP class happens to be 1 of the 2 classes that has this cardiovascular outcomes data.

Troy Trygstad, PharmD, MBA, PhD: That’s an interesting concept, and we’re seeing that more often now where we have a treatment for diabetes, but it’s the outcomes associated with an ancillary or neighboring disease state that are really affecting where it is in the line. That gets to your 8 systems. And so, are we going to see GI [gastrointestinal] data and other types of systems data, the effects of GLP-1s coming out, in research? So, if we’ve got cardiovascular, what about other organ systems?

Susan Cornell, PharmD, CDE, FAPhA, FAADE: I do think so, but I think probably more what we’re going to see in the future is time in range. One of the things we’re looking at is hypoglycemia as a cardiovascular risk factor. The number of hypoglycemic episodes a patient has really puts them at a risk, and so we want to minimize that. But at the same time, we want to minimize the hyperglycemia episodes as well. So when we look at patients, we’re looking at how much time they are within the normal glucose range. So, rather than the organ system that we’re looking at, I think we’re looking at which medication will keep you within a neutral, normal range for the longest period or the greatest period of time.

Troy Trygstad, PharmD, MBA, PhD: So time in range seems to be a little bit more of an advanced version of proportion of days covered, if we’re thinking about it in terms of how we are doing on a timeline and don’t want to see a lot of variation. So the idea is the exposure time out of range, high or low.

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

Troy Trygstad, PharmD, MBA, PhD: And how we are managing patients so they’re in that magic range, just like the little mountain guy on “The Price Is Right.”

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: One thing I’ll add is that I think the other shift that’s happening now is we’re focusing on treating the whole patient and not just the disease. And to Sue’s point, we’re looking at some of these beyond A1C [glycated hemoglobin] metrics, such as time in range and hypoglycemia. But the other thing that is happening with this class of medications and others is they’re starting to look at diabetes-adjacent diseases. And so you’re looking at this and GLP use and the impact from a renal standpoint, and NASH [nonalcoholic steatohepatitis], and obesity. In obesity, there’s already a medication that’s on the market.

I always use this line when I’m giving a presentation: I ask the audience, “What do you think folks with diabetes die from?” And 8 out of 10 of them are dying from cardiovascular causes. And everyone is like, “Well, you know, you did an entire talk and you’re only talking about cardiovascular data. We haven’t even talked about the glycemic.” But, at the end of the day, that’s what I call the needle mover. If you want to move that needle, you need to start focusing on what the population is actually suffering from. I think that’s why there’s now more of a holistic approach in looking not just at the disease, but at that whole picture.

Troy Trygstad, PharmD, MBA, PhD: Right, and it’s not just the adjacent disease, it’s also the untoward outcomes. When we think of diabetes and poor outcomes, we’re thinking of lower leg amputations, blindness, chronic kidney disease, and other problems associated with diabetes. But they’re problems in and of themselves, and are conditions that have to be treated in and of themselves. So what’s interesting to me are those facts that I frequently go back to when we’re writing for Pharmacy Times^®: 70% of the nation’s health care costs are borne by patients with 2 or more chronic illnesses, and 83.2% of the nation’s prescription fills are for patients with 2 or more chronic illnesses. Do we need to be thinking of therapies not in silos based on condition, but what the whole treatment plan looks like for that whole patient, since so many of our patients have these comorbidities?

Susan Cornell, PharmD, CDE, FAPhA, FAADE: I think we also have to look at the obesity factor. How stupid is it when we say, “Oh, you have diabetes. Here’s a medication that will cause you to gain weight, but we want you to lose weight.” We set the patient up to fail. It’s not that the patient failed, the medication failed the patient. So to Dhiren’s point, we want to set the patient up for success by focusing on the whole patient. And Jess, you mentioned, of course, that we’re not only looking at cardiovascular, but we’re looking at weight loss and low hypoglycemia. So again, something that will address more than just those glycemic markers.

Jessica L. Kerr, PharmD, CDE: I think what’s been nice is now with the ADA being more in tune as almost being prescriptive, those guidelines actually help us, as clinicians. Because, oftentimes, when you’re looking at payers or when you’re looking at making those recommendations to those primary care providers or to those specialty services in endocrine or whatever it is, we have those guidelines to support something we have been doing since the data have been coming out. We have always tended to practice the evidence-based medicine, and then you finally have a guideline that supports and demonstrates that. I think that’s going to allow for us to treat that patient as a whole.