GLP-1 Receptor Agonist Treatment Options for T2D



Davida Kruger, MSN, APN-BC, BC-ADM: I want to focus back on GLP-1 [glucagon-like peptide-1] receptor agonists. First of all, I always think of them as a little bit geeky because they work when blood glucoses are elevated, and they turn themselves off when blood sugar is normalized. They are glucose dependent. They delay gastric emptying, as we’ve already mentioned, because patients who have diabetes have rapid gastric emptying. Patients are often saying that they’re hungry, so they overeat because they don’t have a sense of fullness or a sense of satiety. It gives them all of that back, plus it has the cardiovascular benefit and the glucose benefit. Let’s talk a little bit more too about it. In and of itself, it doesn’t cause hypoglycemia. Why doesn’t it cause hypoglycemia? That’s because it’s glucose dependent.

Now, if the patient is on a sulfonylurea, those are pretty nasty. I know they’re cheap, but they’re nasty. If we can get rid of them, because all they do is cause hypoglycemia and weight gain, and the patient benefits more if we can get rid of them. If the patient is already on insulin when we go to give them a GLP-1 receptor agonist, these medications can be lowered. Personally, for the sulfonylurea, I try to get rid of them. With insulin, it depends on the dose. If someone said that they didn’t realize that they could use a GLP-1 receptor agonist before insulin, and the patient is only on 30 or 40 units of insulin, there’s a good chance that patient may not need a basal insulin. If it’s my practice [at the Henry Ford Health System], I would cut them back 20% or 30% depending on where their A1C [glycated hemoglobin] was. As I then titrate the GLP-1, I can look at the blood glucose, look at CGM [continuous glucose monitoring], and I’ll continue glucose monitoring to see if I can get rid of the insulin.

Now if I can’t, then I can’t. But it’s the insulin and the sulfonylurea on board that are going to cause hypoglycemia. Of course, the 2 things the patients hate most are hypoglycemia and weight gain. If I can provide something like a GLP-1 receptor agonist that does not give either to the patient, then that’s a win-win, and I’ll have a happy patient, and they’re more apt to stay with it. We know that there is weight reduction associated with the GLP-1 receptor agonists. We’re probably talking, some patients can get 5 or 10 pounds off with an A1C between 1% and 1.8%, depending on the use of whichever medication. Is that what you typically see in clinical practice?

Lucia Novak, MSN, ANP-BC, BC-ADM, CDTC: Yes. In fact, before GLP-1 receptor agonists and the SGLT2 [sodium-glucose cotransporter-2] inhibitors, I always had to warn patients that, as we get these blood glucoses down, your weight is going to go up. Unless we also put in place the therapies that are required as far as nutritional plans, physical activity, and diabetes education with a certified diabetes care and education specialist, they will gain that weight. That’s the beauty of these medications: we see glucoses go down. We see A1C levels improve. We don’t have a hunger drive due to overinsulinization. We don’t have a hunger drive due to hypoglycemia, so they tend to lose weight as well as get better blood glucose control.

The glucose-dependent way that the GLP-1 receptor agonists work isn’t just on that first day’s insulin. Of course they’re not going to secrete insulin if their blood sugars are down, but that also applies to the alpha cell and glucagon. That is also glucose dependent, so as their blood glucoses come down, they have that ability to respond naturally and normally to a falling blood glucose, like we all do, and secrete glucagon. That’s a problem when they are on a sulfonylurea or insulin because that overrides that safety mechanism, and I’m 100% on board with you there, Davida. I’m taking them off those sulfonylureas. Typically, a lot of patients, especially our patients with type 2 diabetes, may not even take that insulin every day. I’m finding that even a 50% reduction is quite safe to do when you’re adding a GLP-1 receptor agonist or even the SGLT2 inhibitor to that regimen.

Davida Kruger, MSN, APN-BC, BC-ADM: Typically what I say is we’re going to go low, go slow. I’m going to take the patient off more of their insulin than I think they need to prevent low blood sugar, and I can always put it back.

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Transcript Edited for Clarity

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