Corinn Cross, MD (Host): Childhood obesity is a growing problem and puts children at risk for poor health in the future. The CDC estimates that between 2017 and 2020, 14.7 million children were considered obese in the United States.

This is Pediatric Insights, Advances in Innovation with Children's Health, where we explore the latest in pediatric care and research. I'm your host, Dr. Cori Cross. Today we have with us Dr. Sowmya Krishnan, Pediatric Endocrinologist at Children's Health and Professor at UT Southwestern, and she's here to discuss weight loss medications and treatments for children. Welcome Dr. Krishnan. Thank you so much for being here with us today.

Sowmya Krishnan, MD: Thank you for having me.

Host: Let's jump right in. So I'm sure everyone has heard of the weight loss drug, Ozempic. It's all over the television. So weight loss drugs like Ozempic have been trending and it's a topic in the news for all adults, but children also struggle with obesity and childhood obesity isn't always caused by overeating or poor diet.

We know that sometimes there are social determinants of health, genetics, certain medications, or even preexisting health conditions that play a role. Can you share how prevalent is childhood obesity and what are some common misconceptions?

Sowmya Krishnan, MD: According to recent data, approximately 14.4 million children and adolescents have obesity. And thus, this is the most common chronic disease affecting children in this country. One of the most common misconception of childhood obesity is to think of it as solely the result of unhealthy personal choices without understanding the complex interplay of behavioral, environmental, genetic, and metabolic factors that could contribute to this.

So increasingly we are understanding the role of all of these factors that lead to childhood obesity. I would say this is one of the most common misconceptions.

Host: Yeah, no, I would agree with you. So let's dive into specific weight loss treatments and drugs for children. There are several FDA approved drugs being used as treatments for obesity in adolescents, age 12 and older. Could you tell us what they are?

Sowmya Krishnan, MD: At this time, FDA has approved four drugs for treatment of childhood obesity for children age 12 or older. These are 1. Orlistat. Orlistat acts by blocking dietary fat absorption. This was first approved by FDA in 2003 for children age 12 years and older, making it the first drug to be approved for use in children.

At a dose of 120 milligram, three times a day, taken before or up to one hour before each meal, orlistat can block up to 30 percent of fat absorption. But it has significant side effects, including steatorrhea, flatulence, stool urgency, and thus is poorly tolerated, especially in children and adolescents, as you can understand. Malabsorption of nutrients, including fat soluble vitamins, and its effect on growing children is another concern. The other two drugs approved for children or that come under the class of GLP one receptor agonist or the glucagon-like peptide receptor agonist. They are one as liraglutide or Saxendas. This was approved in 2020 for treatment of children age 12 years or older with a BMI for age and sex in the 95th percentile, or greater for age. GLP 1 is one of the several peptide hormones encoded by the proglocagon gene and its primary mechanism of action is through stimulation of insulin release from the beta cells in the pancreas. It also delays gastric emptying and also decreases appetite due to its effect on the hypothalamus and hindbrain.

Liraglutide is given as a daily subcutaneous injection. A dose is started at usually at a lower dose and slowly titrated up to a target dose of 3 mg daily. The second drug that is used in this same class of drugs as semaglutide. And that is given as once a week injection, semaglutide or Wegovy. And this was approved recently this year for treatment of children aged 12 years or older.

The approval was based on a clinical trial that showed 73 percent of children in the semaglutide group had a weight loss of 5 percent or more compared to 18 percent of the placebo group. Side effects of these medications are mainly gastrointestinal side effects including nausea, vomiting, and these are contraindicated in children who have a family history of multiple endocrine neoplasia.

The last group of drug that has been approved by FDA is a drug called Qsymia, which is a combination of phenteramine and Topiramate. And this was approved in June 2022 by the FDA for use in children 12 years or older who fall under the obese category. Phenteramine is a sympathomimetic amine and acts in the hypothalamus and decreases appetite, and Topiramate is also supposed to do the same thing. And in combination, both of them actually are given in lower doses and can lead to weight loss.

Host: Now how does Children's Health determine which of their patients actually should be getting one of these medications or what treatment they should give for a patient who comes in who is obese?

Sowmya Krishnan, MD: That's a very good question, Dr. Cross . So, Children's Health offers all these drugs for children who qualify and the choice of these drugs is really based on patient and family preferences and goals and we use a team based approach including incorporating lifestyle changes to manage weight loss. Tailored approach for the treatment of obesity and its related comorbid morbidities is the most successful to achieve what we want to do. So, any child above the age of 12 years who have been unsuccessful with modifying their weight with just lifestyle modification can be offered this drug.

Host: And I'm assuming as a pediatrician myself, that some of the things that weigh into what is the best choice for each particular patient isn't just their weight or their BMI, but rather their blood pressure, their blood sugar, their cholesterol, any sort of metabolic things that are going on, their family history, correct?

Sowmya Krishnan, MD: Absolutely. Yes. One of that is preference is some two medications, a GLP 1 receptagonist are given as injections, which some children may not want. The Qsymia can cause increased heart rate can be associated with suicidal thoughts and ideation, which may be a contraindication for some patients.

So it's all very individual based approach on what would be the best choice for that patient.

Host: And continuing on that sort of train of thought, are there other, I know you mentioned malabsorption, suicidality; are there other common risks of these drugs that need to be taken into account when you're choosing what to use in a particular patient?

Sowmya Krishnan, MD: Absolutely. Qsymia, for example is contraindicated in pregnancy. And so a pregnancy test is recommended before we start Qsymia. And ideally females of childbearing age should use contraception while they are on this drug.

GLP 1 receptor agonists have a very good is particularly preferred for treatment with type 2 diabetes as it's approved for treatment for both type 2 diabetes and weight loss.

Host: Mm hmm.

Sowmya Krishnan, MD: So, those will be the few things that, that come to my mind when I think of certain things to think about when we choose these drugs. And the GLP 1 receptor agonist drugs are contraindicated if there's a family history of multiple endocrine neoplasia. So, when there is a history such, we don't use those medications.

Host: Now, the GLP 1 receptor agonists, those are the ones that we hear in the news and that are just getting so much attention right now. How much do we have to think about that they seem to work wonderfully while you're on the medication and when you're an older individual and adult, maybe you're not thinking about how long you might have to take this medication. How are we doing with adolescents when they come off this medication? Is it something they can come off or is this something that they are going to be on for life?

Sowmya Krishnan, MD: You know, these medications have been very recently approved for use in children. So I think there is a lot we are going to still learn as we prescribe these medications, but it's, that's why it's so important to emphasize that these medications are not just the end all and cure all. These medications have to be used with lifestyle modification. Meaning change in diet and increase in physical activity. And our hope is that with weight loss with this medicine, then it can be sustained with just lifestyle modification.

Host: I'm so glad to hear you say that because I agree. I think that it's a way to sort of stop the obesity trend from going up while we institute lifestyle modifications, diet modifications, and get other things under control with the hope that we can not have a child on medication for life. Are there other preventative measures aside from well child visits that you recommend providers share with parents?

Sowmya Krishnan, MD: I think certain things that providers recommend which are based on American Academy of Pediatrics guidelines is to decrease the screen time for children, decrease sugary beverage intake, have a good sleep routine and always incorporate changes as a family instead of just prescribing a particular diet or activity to a child and having a family make these lifestyle modifications together would be the few things that I would recommend.

Host: I would agree. Is there one thing that you would want other Endocrinologists to know about childhood obesity since this is your specialty and weight loss treatments for children? Is there something that you wish your colleagues knew?

Sowmya Krishnan, MD: One thing that we're recently seeing is with the approval of these medications, there has been an increase in demand for these drugs and the companies unable to keep up with this demand. So some families and patients are turning to use using compounding pharmacies for getting these medications. As providers, it's very important to know that families are doing that and that compounded medications have actually not been approved by FDA and may have side effects that we are not aware of. So it's important for us to educate the patients of these dangers and to want them to not go that route.

Host: That's a very good point.

Sowmya Krishnan, MD: Thank you, yeah, and also avoid over the counter unapproved medications for weight loss. It would be one thing that I would recommend providers educate families on.

Host: Right, lots of people don't realize that if it's coming in as a vitamin or nutritional supplement, it's not necessarily FDA approved.

Sowmya Krishnan, MD: Uh huh. Exactly.

Host: Well, as we wrap up, is there anything you'd like to share or give us a 30 second sort of take home message?

Sowmya Krishnan, MD: I think it's important to recognize that obesity has been stigmatized so far as it was thought to result from poor personal choices. And we, as practitioners, we have to understand the complex genetic, physiological and socioeconomic and environmental contributors to obesity. Social determinants of health impact obesity and obesity related comorbidities, and it's up to us to recognize that and help these at risk children to prevent obesity related comorbidities.

Host: Thank you so much, Dr. Krishnan, for taking the time to share your expertise with us today. This has been such an educational discussion. Thank you.

Sowmya Krishnan, MD: Thank you for having me.

Host: To learn more about Children's Health, nationally recognized Pediatrics Endocrinology Program, visit childrens.com/endocrinology. Thank you so much for your time today with us and to our audience for listening to Pediatric Insights Advances and Innovations with Children's Health, where we explore the latest in pediatric care and research. You can find more information at childrens.com. And if you found this podcast helpful, please rate and review or share the episode and please follow Children's Health on your social channels.