Andrew Bzowyckyi, PharmD, BCPS, CDCES, associate professor at Pacific University Oregon and clinical pharmacist at Legacy Medical Group discusses the differences between GLP-1 receptor agonists and insulin for diabetes management.
Q: What are the characteristics of different GLP-1 receptor agonists for diabetes?
Yeah, so there’s a lot to think about when you have GLP-1 receptor agonists. A few of the ones I can think of are dosing frequency. So we have some that are daily, some that are weekly titration programs, some you can step up one more time, weekly, some monthly, we have fixed dose pens, and we have titratable pens, we I have single-use pens, so you use it and throw it away, you have multi-use pens, so you use the same pen multiple times, you know, some patients prefer one over the other.
You have, obviously, most of them are injectable. We now have an oral GLP-1 receptor agonist, and so we have different dosage forms and needle considerations. So some are co-packaged with needles, some are not, some have a thicker needle size, and there are so many different things to think about.
And then obviously the status of the cost form is going to be huge and then the impact on weight loss, some are more effective in losing weight, some less effective. And so, taking that into consideration will always be important as well.
Q: What insulin treatments are currently available? Are there new treatments in preparation?
Yeah, so insulin is something that’s been around for what seems like forever. For a very long time, there were not many developments. And then you know, all of a sudden, it all came together. Some of the most recent developments are probably at the extremes of our durations of action.
So we have a lot of growth in ultra-fast. Almost immediate-acting insulins, and then at the other end we have more, obviously, ultra-long-acting ones. So those are probably the 2 biggest recent developments. We are seeing a lot more biosimilars, especially Glargine. For example, long-acting insulin, another biosimilar agent, has just been approved. And then we still have the rest of our arsenal.
So, fast-acting insulin, short-acting insulin, intermediate-acting insulin, and then some long-acting insulins as well. And then don’t forget these premixes that they kind of bring back issues with insulin affordability and dosing flexibility, trying to kind of lower those overall doses. We have our premixes, of which I always forget the basal GLP-1 combos. So we still have to have them as well, in terms of new insulin treatments.
Q: What are the differences between insulin and GLP-1 receptor agonists?
Some things. So there are a few once-a-week basal insulins that are in phase three development, and then there’s at least one in phase two trials. So it would be really interesting to see how that plays out. And a little what the patient’s reception is at a basal insulin once a week.
It’s a huge game changer in this space, and then there’s also oral insulin. It is currently in phase three testing. So there’s a lot to come in this area to try and get insulin, which I don’t know of that just have different characteristics because again the more options we have the better for the patients.
So the difference between the 2 is really how I describe it to patients, because I have this conversation all the time, you know, when you’re thinking between the 2, introducing them both to the patient, insulin really helps to supplement the needs of the body.
So it goes straight to the source. It’s more direct and essentially replaces what your body may be lacking or not getting enough of. And then GLP-1RA is, on the other hand, they target the growing system. They help promote endogenous insulin production, but they are not insulin themselves, and this is an important concept to emphasize for patients who may be nervous about starting insulin. Not that it’s a bad thing, but some people thinking you know you’re promoting your endogenous insulin is sometimes a little more acceptable to a patient.
And then on top of that they offer other beneficial effects of this growing system. So delayed gastric emptying, promoting satiety, suppressing gluconeogenesis. You kind of get the multi-factors there, whereas the insulin just goes, you know, straight to the source. It’s very direct, and both have advantages, and both have disadvantages.
Q: When should a pharmacist consider initiating a GLP-1 receptor agonist instead of insulin?
If you look at the American Diabetes Association (ADA) standards of care, which were recently released, but even the latest offerings, GLP-1 really should be strongly considered in patients as a first injectable. Before adding basil, you really have to think about it. And again, before you add a bolus, so if you haven’t added it yet, you know, think about it.
Then the GLP-1 ARs, they sort of provide overall benefits, so weight benefits, cardiovascular risk benefits, certain agents, but kind of like a class as well. There is a low risk of hypoglycemia, so a lot of different benefits there.
However, of course, there are contraindications. There may be barriers to access and there will always be intolerances. And so GLP-1s aren’t for everyone, but it’s certainly considered kind of a first line before, not necessarily the first line, but before you start basil or bolus insulin, because that provides in sort of a complete set.
Q: Why might patients want to prioritize GLP-1RA or insulin over alternatives?
Yeah, and so that kind of speaks to what I was describing earlier where there are, there are pros and cons for both. For insulin, the priority is really for patients who suffer from glucose toxicity, or if you suspect a serious insulin deficiency state. So significantly elevated glucose standards recommend over 300, you know, over 10 signs and symptoms of catabolism. Frequent thirst, frequent urination, where even though you think the patient might have type 1 diabetes, or a lot of latent autoimmune diabetes, in adults, any kind of situation like that, your first jump should be towards insulin.
And then if it’s true glucose toxicity and the initial glucose is clear the patient may not need to be on insulin indefinitely, that could be something you can rearrange the treatment later. On the other hand, so for GLP-1s, think about overweight, obese patients, looking to lose weight, if you think overeating, snacking, or portion size might be a concern. This is another area of help, so rather than giving insulin to treat overeating and snacking, we can give GLP-1 to help prevent overeating and established atherosclerotic cardiovascular disease.
Again, some of the GLP-1 receptor agonists have specific indications either to establish cardiovascular disease or you know, if there are high risk indicators, another time to consider them versus insulin . So there’s really kind of a research between the 2. There’s, again, pros and cons for both and so really looking at that specific patient to see what their needs are and then finding them an agent that can help meet these needs.
Q: Any final thoughts?
Yeah, the other thing I really want to point out is GLP-1 in basal insulins, although prandial insulins are really some of the different agents that we have. And that was just the very specific focus of my talk, but in no way does it mean ignoring the other agents that we have, in terms of SDLT-2 inhibitors, metformin, TZD, all classes of drugs that we have considered useful purpose, and so I think it is important to mention it.
My speech was very focused, but it’s important to think about all the different options available to us when treating patients.