Rationale for GLP-1 Therapy in T2D

Experts review the mechanism of action of GLP-1 agonists in type 2 diabetes and remark on their role in treating appropriate patients.

Troy Trygstad, PharmD, MBA, PhD: Hello and thank you for joining this Pharmacy Times® Peer Exchange titled “The Benefits of GLP-1 Agonists for Type 2 Diabetes.”

Over 29 million people, or the equivalent of 9.3% of the US population, have diabetes. Type 2 diabetes [T2D] mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. While there are a lot of treatment options available to help manage glycemia, we would like to focus this Peer Exchange on the role of GLP-1 [glucagon-like peptide-1] agonists. The GLP-1 hormone is partly responsible for insulin release and for attenuating hyperglycemia during meals, and therefore, GLP-1 agonists have emerged as an attractive treatment option for patients with type 2 diabetes. Let’s review the available agents and benefits they provide in the treatment plan for type 2 diabetes management.

I am Dr. Troy Trygstad, and I am the vice president of Pharmacy and Provider Partnerships at Community Care of North Carolina in Raleigh, North Carolina. I’m also the editor-in-chief of Pharmacy Times^®.

Participating today on our distinguished panel are: Dr. Susan Cornell, associate director of experiential education and an associate professor in the Department of Pharmacy Practice at Midwestern University Chicago College of Pharmacy in Downers Grove, Illinois.

We also have with us Dr. Jessica Kerr, interim associate dean of Professional and Student Affairs and professor in the Department of Pharmacy Practice at Southern Illinois University Edwardsville School of Pharmacy in Edwardsville, Illinois.

And finally, we have Dr. Dhiren Patel, associate professor of pharmacy practice at MCPHS [Massachusetts College of Pharmacy and Health Sciences] University, and clinical pharmacy specialist at the VA Boston Healthcare System, in Boston, Massachusetts.

Thank you so much for joining us. Let’s begin.

Let’s get started with the most simple question, perhaps, or the most straightforward question. What is the mechanism of action of a GLP-1 agonist? Susan?

Susan Cornell, PharmD, CDE, FAPhA, FAADE: I like to always talk to folks as if I’m talking to patients, and I like to explain things in a very simplistic fashion. If we think of GLP-1, what is it? It’s a natural hormone our body makes. And just like insulin, again, a natural hormone. The problem is with hormones, as we know, it’s very difficult to get a synthetic version of it. So in this particular case, of course, what we have is what I call a pharmacological dose of our natural GLP-1. So it’s like our natural GLP-1 on steroids. It’s 10 times more potent than what our bodies are making.

And so, the question then comes along of, what does GLP-1 do? If we look at the ominous octet of diabetes, or the 8 broken organs, shall I say, of diabetes, the nice thing is the GLP-1 agonists actually fix 6 out of 8 broken organs. So not only are they regulating insulin production, they’re also regulating amylin production out of the beta cell. So we’re fixing the beta cell, and then at the same time, we’re fixing the brain because it’s creating satiety by fixing amylin production. It also works on the alpha cell, and by doing that you’re actually regulating glucagon production because we find that many people with type 2 diabetes have an overproduction or hyperglucagonemia. And by regulating glucagon we’re now fixing the liver which, of course, allows the release of glucose from the liver.

Next, of course, we’re fixing insulin resistance. We’re losing weight. By doing that, insulin is being used more appropriately. And then, of course, my personal favorite, is that it fixes the GI [gastrointestinal] tract. Because, if we think of people with type 2 diabetes, they have a very quick digestion of food, which sounds a little weird. But, because of that quick digestion, we’re getting increased postprandial spikes. And so these slow it down, or make it a little bit easier to do. So, basically, simply stated, GLP-1 agonists fix 6 of the 8 broken organs in the defects.

Troy Trygstad, PharmD, MBA, PhD: So this all sounds very sophisticated. When I grew up in pharmacy school it was metformin and insulin. So, Dhiren, how much of an advance are these new types of therapies for the treatment of diabetes?

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: They’re all new within the last 5 to 10 years. I think for everyone on this panel, we’re in the same boat. This class didn’t exist. The DPP-4s [dipeptidyl-peptidase-4s] didn’t exist. The GLP, the SGLT2 [sodium-glucose cotransporter 2] classes didn’t exist, and they’ve been elevated in a lot of the guidelines that we’re going to be talking about later today. And part of the reason is the mechanism of action. They’re working in more than 1 way. If you think about sulfonylureas, basically you’re squeezing your pancreas to push out more insulin. And here you have these medications that are working in a more sophisticated manner in response to glucose, where they’re not just indiscriminately lowering blood sugars. And so, because of that, they’ve started getting a lot more traction.