Expert Discusses GLP-1 Receptor Agonists for Treatment of Diabetes

Andrew Bzowyckyi, PharmD, BCPS, CDCES, associate professor at Pacific University Oregon and clinic pharmacist at Legacy Medical Group discusses the differences in GLP-1 receptor agonists and insulin for the management of diabetes.

Q: What are the characteristics of different GLP-1 receptor agonists for diabetes?

Yeah, so there's a lot of things to think about when you've got the GLP-1 receptor agonists. A couple of the ones that I think of are dosing frequency. So we've got some that are daily, some that are weekly titration schedules, some, you can step up kind of, again, weekly, some monthly, we've got fixed dose pens, and we've got titratable pens, we've got single use pens, and so you kind of use it and throw it away, you've got multi use pens, so you use the same pen multiple times, you know, some patients prefer 1 over the other.

You've got, obviously, most of them are injectable. We've got an oral GLP-1 receptor agonist now, and so we're getting different dosage forms and needle considerations. So, some are co-packaged with needles, some aren't, some have like a thicker needle size, and so lots of different things to think about.

And then obviously, cost formulary status is going to be huge, and then weight loss impact, some are more effective at weight loss, some are less effective. And so taking that into consideration is always going to be important as well.

Q: What insulin treatments are currently available? Are there any new treatments in the pipeline?

Yeah, so insulin has been something that's been around for what seems like forever. For the longest time, there weren't a whole lot of developments. And then you know, all of a sudden everything hit. Some of the most recent developments are probably on the extremes of our durations of action.

So, we're having a lot of growth in the ultra-rapids. The almost immediate acting insulins, and then on the other end, we're having more, obviously, ultra-long-acting. So those are probably the 2 biggest developments recently. We're seeing a lot more biosimilars, specifically Glargine. So long-acting insulin, another biosimilar agent was just recently approved. And then we've still have the rest of our armamentarium.

So, the rapid insulin, short insulin, intermediate, and then some long-acting insulins as well. And then don't forget those premixes they're kind of making a comeback with insulin affordability issues and flexibility of dosing, trying to kind of reduce those overall doses. We have our premixes, including I always forget about the basal GLP-1 combos. So, we still have to have those as well, in terms of new insulin treatments.

Q: What are the differences between insulin and GLP-1 receptor agonists?

A couple things. So, there's a few once weekly basal insulins that are in development one's in phase three, and then there's at least 1 in phase two trials. So, this would be really interesting to see how this plays out. And kind of what the patient reception is to a once weekly basal insulin.

It's a huge game changer in this space, and then there's also an oral insulin. That's currently in phase three trials. So, lots to come in this area trying to get insulin, that I don't know that just have different characteristics, because again, the more options we have the better for patients.

So, the difference between the 2 is really the way I describe it to patients, because I have this conversation all the time, you know, when you're thinking between the 2, presenting them both to the patient, insulin really helps supplement the body's needs.

So it just goes straight to the source. It's more direct, and basically replaces what your body may be missing or may not have enough of. And then GLP-1RA is, on the other hand, they're targeting the increasing system. They help promote endogenous insulin production, but they're not insulin themselves, and that's an important concept to emphasize to patients who may be nervous about starting insulin. Not that that's a bad thing, but some people thinking that you know you're promoting your endogenous insulin is a little bit more palatable sometimes for a patient to process.

And then on top of that, they offer other beneficial effects from that increasing system. So delayed gastric emptying, promoting satiety, suppressing gluconeogenesis. You kind of get the multi-factors there, versus insulin just goes, you know, straight to the source. It's very direct, and both have pros, and both have cons.

Q: When should a pharmacists consider initiating a GLP-1 receptor agonist instead of insulin?

If you look at the American Diabetes Association (ADA) standards of care, that are recently published, but even the last couple offerings, really the GLP-1 should be strongly considered in patients as that first injectable. Prior to adding basil, it should really be considered. And then again, prior to adding bolus, so if you haven't added it yet, you know, thinking about it.

Then the GLP-1 RAs, they really kind of provide that overall package deal benefits, so benefits on weight, benefits on cardiovascular risk, certain agents, but kind of as a class as well. There's a low hypoglycemia risk, so lots of different benefits there.

However, obviously, contraindications exist. There can be barriers to access and then there will always be intolerances. And so GLP-1s aren't for everyone, but it's certainly considered kind of first line prior to, not first line necessarily, but prior to starting either basil or bolus insulin, because it kind of provides a whole package deal.

Q: Why might patients want to prioritize GLP-1RA or insulin over the alternatives?

Yeah, and so this speaks a little bit to what I was kind of describing previously where there's, there's pros and cons to both. For insulin, really the priority there is for patients who are experiencing glucose toxicity, or if you suspect a severe insulin deficient state. So, significantly elevated glucose standards recommend over 300, you know, agency over 10, signs and symptoms of catabolism. The frequent thirst, the frequent urination, where even if you think the patient might have type 1 diabetes, or lot of latent autoimmune diabetes, in adults, any type of situation like that, kind of your first jump should be towards insulin.

And then if it is a true glucose toxicity, and initial glucose is clear, the patient may not need to be on insulin indefinitely, it could be something that you can rearrange the treatment later. On the other hand, so for the GLP-1s, thinking overweight, patients who are obese, looking to lose some weight, if you suspect overeating, snacking, or portion sizes might be a concern. This is another area to kind of help so rather than kind of giving insulin to treat the overeating and the snacking, we can give a GLP-1 to help kind of prevent the overeating and then established atherosclerotic cardiovascular disease.

So again, some of the GLP-1 receptor agonist have specific indications in either establish a cardiovascular disease, or you know, if there's indicators of high risk, another time to consider these over insulin. So really kind of looking between the 2. There's, again, pros and cons to both and so really looking at that specific patient to see what their needs are and then getting them an agent that can help meet those needs.

Q: Any closing thoughts?

Yeah, the 1 other thing I just really want to emphasize is the GLP-1 in the basal insulins, even though the mealtime insulins are really a few of the different agents that we have. And that was just the very specific focus of my talk, but do not in any way mean to disregard any of the other agents that we have, in terms of SDLT-2 inhibitors, Metformin, TZD, every medication class that we have considered valuable purpose, and so I think that's important to mention.

My talk was very focused, but it is important to kind of think about all of the different options we have when we're treating patients.