Guidelines and Patient Factors for GLP-1 Agonists

Provide an overview of the role of GLP-1 agonists in the new treatment guidelines.

Tripp Logan, PharmD: When GLP-1 [glucagon-like peptide-1 agonists] first came out, what we experienced was a little reluctance to jump in with them. As they’ve been out on the market for a longer period of time, and more research has been done on them, guidelines have been changed. And now GLP-1s are really early initiators in diabetes treatment guidelines. Which in my experience has been a very positive thing, and we’ve seen positive results with this addition.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: The 1 major difference that we’re seeing in the newer guidelines, specifically the 2019 ADA [American Diabetes Association] guidelines as well as the 2018 ADA/EASD [European Association for the Study of Diabetes] consensus report is the elevation of the GLP-1 receptor agonists within the treatment algorithms. The AACE [American Association of Clinical Endocrinologists] guidelines have always supported that after metformin that you consider a GLP-1 receptor agonist as a second line or third line in addition to metformin. But a big change we’re seeing from the likes of the ADA—where now after 3 months, folks are being asked if patients have established cardiovascular disease and are considering agents that have proven cardiovascular outcomes data, including GLP-1 receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors. The ADA/EASD consensus report went as far as to say that if you’re going to consider an injectable, let that first injectable be a GLP-1 receptor agonist.

And the reason you keep seeing these medications being elevated within the guidelines is for a variety of reasons, just beyond their ability to lower blood sugars. Yes, they’re going to lower their blood sugars, but they’re helping patients lose weight. It’s having a positive impact on their kidneys. And so going back to those comorbid conditions that we were talking about, especially cardiovascular disease, now you’re taking care of the whole patient and not just the disease, and so that’s why you’re seeing multiple mechanisms of actions of these agents, as well as multiple cardiovascular mechanisms of actions of how they’re producing their benefit.

Tripp Logan, PharmD: When patients present to their prescriber for treatment in diabetes, there are a lot of different options and ways to go. Oral is typically preferred by most patients who we see because injectable medications are—there’s a stigma or they’re intrusive, and it’s often a personal concern and a fear for patients who we see. That doesn’t necessarily mean that the oral is the best option for that patient, but it is a barrier that we have to consider and potentially overcome.

GLP-1s have, when they first came out and they were first in the market, we didn’t see a huge uptake in the utilization from the prescribers that we worked most closely with. And I think that’s for several reasons. One is that there are a lot of unknowns. I don’t think that prescribers fully understood the benefits of the GLP-1s in the beginning.

Prescribers who approached patients with new treatment options like GDP-1s often saw resistance because GLP-1s, being injectables, were seen as insulin. And there was a learning curve with that. Over time what we’ve seen is that prescribers in our area that we work with regularly have become much more comfortable in prescribing these because, 1) they’ve seen the benefits of it; and 2) they’re much easier to prescribe than insulin because the dosing is much more simple. Whether it’s twice a day, once a day, or weekly, it doesn’t require blood glucose checks as insulin does. It is a month’s supply that can be prescribed, and the dosing is very simple.

This has resonated really well with our local prescribers, especially since in the guidelines these are to be used earlier and can be used much earlier. Patients who 5, 10 years ago were very reluctant to use injectables now have really become much more open to this based on prescriber comfort level with talking about these.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: There are factors that should be considered before initiating a GLP-1 receptor agonist, and some of them include a prior history. If a patient has pancreatitis, those would be patients that you would not want to initiate on the medication. There are some specific warnings regarding thyroid cancer, and so specifically we’re looking at MTC [medullary thyroid cancer] or MEN2 [multiple endocrine neoplasia type 2], which are rare. They’ve seen these issues in both genders of rats and mice, but it hasn’t translated into humans. So if there’s a family history of that or the patients themselves have it, those would be patients who you would want to exclude from putting on this drug class. Some precautions are patients with a history of gastroparesis—because the way the medication works, it slows gastric emptying.

So most of them are ones that you can talk to your patient, making sure that you counsel appropriately and there are not going to be limitations of being able to start that patient on a drug. The biggest adverse effect to kind of look out for are GI [gastrointestinal]-related adverse effects, so nausea and vomiting. With all the medications, you want to slowly titrate the medications, and so that kind of minimizes some of that stomach upset. But again, it’s important to kind of put that bug in that patient’s ear and say this is going to happen. I need you to work with me for a couple of days a week, and it’s going to get a lot better. So I would say those are probably the main ones to consider when starting a GLP-1 receptor agonist.