Corinn Cross, MD (Host): Welcome to PedsCast, A podcast brought to you by Children's House. School of Alabama in Birmingham. I'm your host, Dr. Cory Cross. Thank you for joining us today. We are joined by Dr. Giovanna Bamp and Dr. Al Resnick from the endocrinology department at Children's of Alabama And the University of Alabama at Birmingham.

We are gonna have an interesting discussion on glucagon-like peptide one receptor agonists, which is quite a mouthful, better known as GLP one receptor agonist. Dr. Amp and Dr. Resnick will be assessing GLP one receptor agonist potential effectiveness for patient's with type one diabetes. Thank you for joining us.

Ortal Resnick, MD: Thank you for own us.

Giovanna Beauchamp, MD: Thank you very much for having us. We appreciate it.

Corinn Cross, MD (Host): Of course. So in discussing type one diabetes, maintaining glycemic control is obviously paramount to good care. How challenging is it for patient's with type one diabetes to maintain glycemic control with the currently available treatments?

Giovanna Beauchamp, MD: unfortunately it is, pretty difficult to achieve, good diabetes control with current treatments. We do wanna say, thankfully for the last a hundred years, we've had insulin, insulin is the gold standard. It's the mainstay, therapy for, type one diabetes. And we've also had, of course, so many advances in terms of technology with insulin pumps, with continuous glucose monitors, with automated insulin delivery systems.

Yet despite all of this. We are still achieving good control per all of the standards in about 20% of our patient's. So that still means that about 80% of our patient's are actually not achieving good glycemic control with current standards, and This is why it's time to add something else.

Corinn Cross, MD (Host): That's a large percentage. Now, in addition to glycemic control, which is a challenge, weight and obesity can also be a challenge for some patient's with, type one diabetes. Can you explain those issues and how much of a concern weight gain is in these patient's?

Ortal Resnick, MD: So actually weight gain is a big issue with type one diabetes. It's like, was. Thought that Type one diabetes are lean and tend to lose weight. But actually we know now that obesity is a big issue. In about 60% of the population with Type one are suffering from overweight and obesity, And we know that insulin by itself is an anabolic hormone that causes weight gain and on average.

Patient that start on insulin treatment gained five kilograms in the first five years of treatment. So we know that the treatment by itself cause weight gain. In addition to that treating and preventing hypoglycemia, mean that you need to, every time that you have low, you need to eat carbs and, you need to eat.

Very organized. It a lot of times calls you to consume more carbs And then you need more insulin it's like this vicious cycle that you keep gaining more weight. And as we gain weight, we have more insulin resistance, so we need more insulin. And again, we know now we understand that type one diabetes going, correlation with obesity.

And we also understand that obesity by itself increase the inflammation, increase the beta cell destruction. That beta cell needs to deal with more, And so they ended up to have more severe diabetes earlier in their course.

Corinn Cross, MD (Host): So obesity is something obviously that we want to avoid. it's basically one of those things that isn't just a problem's. A problem down the line. 'cause it causes the disease to progress faster.

Giovanna Beauchamp, MD: And it also makes it difficult or harder to treat. Absolutely.

Corinn Cross, MD (Host): it. Right, because you end up chasing your tail with needing more and more insulin. So can you explain the role of GLP one receptor agonists in patient's with type one diabetes and or obesity?

Ortal Resnick, MD: So GLP one is a hormone secreted in our body, helping us, control our insulin sensitivity and help us feel more full, after we eat. And so by giving it as a treatment is a receptor agonist, it's helping us to, increase this effect. And so we know it's very efficient with obesity and with type two diabetes because again, it helps our.

Gly semi control and it helps also to lose weight. And this factor is exactly what we want in type one diabetes. We want that as well, that the insulin that we give will work better. And also, as we just discussed, we want the weight loss because, You know, obesity by itself is, crucial in the management And the prognosis of type one diabetes.

these treatment we think are going to be very helpful in managing type one diabetes.

Corinn Cross, MD (Host): Now, can I ask you just a question about GLP ones in general? So they work by both what you said, making the insulin more. Effective, but they also work by curbing your appetite. How in type one diabetes, because as you discussed before, they need to eat on a regular basis to maintain that glycemic index.

How do you sort of reconcile those two things?

Giovanna Beauchamp, MD: when GLP ones are used in type one diabetes, they still help her appetite, right? Which is again, from central mechanisms in your brain. And the good thing is you end up. Eating less fewer calories, which then leads to weight loss. As you lose weight, your insulin requirements then are also lower right As you eat more.

And you gain weight, then you have more adiposity. This increases insulin resistance, which then makes you gain more weight, which then makes you need more insulin, which then increases more insulin resistance, which is going back to that feedback loop that Dr. Resnick was talking about. And so in type one diabetes, if we can.

Hit it centrally, open your brain with curving that appetite. Then we end up eating less and eating less insulin, which then we know has good benefits in our hearts And in our kidneys, And so on And so forth.

Corinn Cross, MD (Host): You're able to switch their path from one where there it's obesity driven. To one where you're actually able to control their appetite, decrease the obesity, and therefore get the disease in better control, which will have less effects down the line of kidneys, eyes, all the other issues that we have with diabetes.

Giovanna Beauchamp, MD: Right.

Ortal Resnick, MD: On top of that, that. we don't need to eat regularly to control the diabetes. We just need to make our sugar stable. It is important, and it's a good note to mention that when we are decreasing the appetite, we need to make sure that our nutrition will be balanced and will be good because it.

Very easily you can become mal malnourished if you decrease your appetite and you eat only non nutritional food. So it's a great point and it's a good point for everyone. Everyone who's on GLP one treatment, we always need to make sure that they're eating balanced meals and they have older nutrition values and.

Type one diabetes. Not exceptional to that. It doesn't mean that when you have type one, you have to eat in a schedule routine. We do ask our patient to do it just because it makes the insulin injection be easier to monitor because you need bowls before you eat. So it's better when you have a routine, so you're able to control it, but it's not necessary that you have to eat more food to control your diabetes.

Corinn Cross, MD (Host): That makes sense. And that's a great segue into what I'd like to talk about next, which is the safety And the side effect profile, which is what you're touching on the fact that you need to continue to have a. Well planned and well balanced diet because you're eating less.

That applies to everybody whether you have type one diabetes or not. The fact that GLP ones are naturally occurring hormones in our body means that we're putting something in that our body is actually already used to. So that all being said, what do you see as the most typical side effects of patient's who are using this?

Are there any adverse effects that anyone should be concerned about? Could you discuss that a little bit?

Ortal Resnick, MD: The most. Side effect that we see with, GLP one use in all the groups is nausea and vomiting. and That is because the GLP one slow down are gastric empty, um, people that are used to it, big portions. With the slow gastric emptying will cause them nausea and vomiting.

So the best way to manage it is to eat smaller portions and to decrease the fat in them, And that helps with this side effect. Another thing is to increase the dose of the GLP one gradually and slower. Really help to fight to against this side effect. And another thing That is been reported in research as side effect is decreased appetite, but That is actually our goal.

So I don't see it as side effect as much. That is part of what we are. Want to get from the treatment. when we are thinking about type one diabetes, the reason that we are more questioning the treatment is because there was a concern about hyperglycemia and about hyperglycemia because we are decreasing the insulin.

how will it affect glucose balance, so about hyperglycemia. the literature shows that it's not increasing. It actually has less hyperglycemia and less DK, a diabetic ketosis event. So in that sense, I feel pretty comfortable with my patient for the hyperglycemia because the insulin works better And we are losing weight And we need less insulin.

We are prone for hyperglycemia. So the way to manage it, and again, we just need to be aware of that, that it can cause hypo lyin And we need to treat with less insulin. And to find this fine balance of how much insulin do we need. And not to cause hyperglycemia.

This is something that, This is why we are seeing our endocrinologist when we are doing it, and This is why we are monitoring and This is why we are checking, And we will decrease the insulin initially and decrease it as needed to prevent this hyperglycemia.

Corinn Cross, MD (Host): Now, these are medications that people are on basically most of the time for the rest of their lives. Now, patient's with diabetes are used to that already because they're going to have to be taking insulin for the rest of their lives. So This is just a lifestyle situation that they have to deal with because the beta cells in their pancreas aren't working correctly.

So we have to give them things to fix this. That being said. I've read that there are concerns or there are theoretical concerns with being on like a GLP one for the rest of your life. Does that play a role at all in type one diabetes And the treatment?

Giovanna Beauchamp, MD: I don't know that we have all the long-term data yet to necessarily be able to comment on that. it is very likely that these are gonna be lifelong treatments just because we will see that the benefit in. obesity And in decreasing complications more so than the benefits in A1C And in time and brain, We will see all of the benefits, but whether our patient's are gonna have to be on medicine lifelong or not, I think it, it may be too early to comment on that.

Dr. Resnick may have another comment.

Ortal Resnick, MD: Just to add to that, we are using GLP one for type two diabetes for about 20 years now. to know about long-term, like lifelong information. We just don't have this data. Like there is not enough time, to see for what we know from the last 20 years is that it's pretty safe.

There is also dose change. There is the dose that you use to lose weight, And then there is like the maintenance dose that a lot of times we are decreasing the dose to keep the same weight because we don't want to lose more weight. And so This is also a lot of question that we need more time to know.

Giovanna Beauchamp, MD: We need more time. Time, And we need more research, right? Because we are now extrapolating data and it's, difficult to compare these studies And we should not, right? Because we are comparing different populations, different study sizes, we are not necessarily comparing things that are. Easier Correct. To compare, but we can only extrapolate from what we have in type two studies and obesity studies And in type one studies with, small sample sizes.

And so we are extrapolating all of the safety that we can from that.

Corinn Cross, MD (Host): Right. And that segues into really what, you have been doing. So you wrote a mini review about GLP one, receptor agonists in patient's with type one diabetes. Um. But again, the n is small because there isn't a lot of research, That is, being done and, you really had to extrapolate data.

How did you go about assessing the effectiveness of GLP ones in, receptor agonists in these, patient's? And what did your, mini review sort of show.

Ortal Resnick, MD: We did a literature review looking at both pros, retrospective and randomized clinical trials, And we analyzed our data mostly from the randomized control trials, understanding that when we are comparing it to placebo, we're getting a more reliable information. you are right that there is not a lot of literature And also most of the literature that has been done, was done on an old GLP one, which was a daily GLP one.

We know now that we have a better weekly, stronger medication that works better for type two diabetes, And we are expecting them to work also better for type one diabetes. But we analyze this around 12 articles that have been done, um, on Type one Diabetes. Some of them are small with like just 18.

patient, but some are with 1400. So there are some big research that's been done on Type one diabetes And then we analyzed what are the result, how it affect the A1C, the weight. they also looked a little bit about the eptide, which shows us the beta cell effect. There is assumption that with, early start of the GLP one, we may help with a better cell load and help to preserve some better cell function.

but again, all of That is. Need to be researched And this, you need to catch the patient very early in the disease so that, again, a lot of future direction And we cannot make assumption based on these studies. but definitely, like we mentioned, it, helps a lot with weight loss, improve A1C.

the A1C is improving but it's only in around 0.3%, which. All patient with type one diabetes will tell you This is the, my difference between my different visit. It not necessarily means a lot, but the fact that they're losing weight and their total daily insulin is decreased. This is a big, outcome that we think will affect their long-term complications.

And again, to be able to look at the microvascular there, risk we need to longer research, which we don't have yet.

Corinn Cross, MD (Host): Right. I mean, to your point, What we're really trying to deal with isn't just the change in hypoglycemia or the blood, the glycemic, control. During the day, but also these patient's, because as a pediatrician, I think of what happens to them down the line. We're thinking about their eyes, their kidneys.

these are all organs that we wanna preserve, with their vasculature for as long as possible. So anything you can do to preserve That is huge. Even if you're not seeing the change in the A1C.

Giovanna Beauchamp, MD: Absolutely. And if, I can make a quick comment on that. The best way that we are gonna see improvement in those potential complications is by decreasing the amount of insulin that our patient's will need, right? Because again, in a lot of insulin around increases adiposity, And then This is what directly causes all of these complications.

In our hearts, in our kidneys, And so through this, decrease in our total daily dose of insulin, that's how we're gonna achieve a lot of success.

Corinn Cross, MD (Host): So last question really is these treatments, they seem to, I think you've explained how they'd benefit patient's with type one diabetes going forward. both in the terms of glycemic control and weight management. Despite the studies being small, I am assuming that it's being used off-label or it's being used more than it's being even researched in these patient's because they have the comorbidities of type one diabetes and obesity.

Can you speak to that a little bit?

Giovanna Beauchamp, MD: Absolutely. we are definitely, we are seeing the rise in the use of GLP ones in type one diabetes. and a lot of it as you very well said, is, off-label. think that when we all believe in the benefit of GLP ones in diabetes in general, And in our patient's who have type one diabetes And also live with obesity, we definitely see.

Absolutely the benefits there. We know that there has been an increase in its use from the last five years till now. the rise has been significant among pediatricians and among endocrinologists for sure.

Corinn Cross, MD (Host): In summary, can you give us a 32nd take-home message for our listeners? Dr. Resnick, do you wanna go first?

Ortal Resnick, MD: sure. Thank you. I think my take-home message is Obesity is a big issue in type one diabetes. we need to change our, set of mind that, only type two diabetes correlate with obesity, And we need to find good treatment for weight loss, to better, regulate semi control. as we are doing very good with the treatment we have now, but not good enough.

20% from our population, getting timing range is just not enough.

Corinn Cross, MD (Host): Dr. Boche, is there something you wish that other endocrinologists knew to make them feel more comfortable in using this type of treatment with their patient's?

Giovanna Beauchamp, MD: I wish that, we all felt. A little bit more comfortable using GLP one therapy in type one diabetes because I do think that those of us who have used it off-label or for the use of obesity, we see wonderful benefits in our patient's, and I think they are all very pleased with those results, which then leads to better diabetes control, And then overall better outlook in life And in being able to live a healthy and happy life.

I think that There are very great ways And we don't have algorithms for, you need to follow this specifically for every patient. Of course, we wanna individualize care. but there are very great ways of doing this and doing it safely for patient's without causing, a lot of hypoglycemia or ketosis or any of the other, potential.

Corinn Cross, MD (Host): Well. Are both for joining us today. This has been a very thought provoking discussion. I know I've learned a lot. I'm sure our listeners have too. for more information or to refer your patient's to Children's, Alabama, please visit children's al.org. That's children's al.org. That concludes this episode of Children's of Alabama PedsCast.

If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library For other topics that might be of interest to you. Please remember to subscribe, rate. End review this podcast. Thanks for listening to this episode of PedsCast. I'm your host, Dr. Cory Cross.