Experts Discuss Benefits, Limitations of Pediatric Obesity Interventions

During a session at the at the 18th annual World Congress Insulin Resistance, Diabetes & Cardiovascular Disease presented by the Metabolic Institute of America, experts outlined the benefits and limitations of pharmacological, surgical, and lifestyle interventions for pediatric patients with obesity.

In the United States, obesity affects 1 in 5 children and adolescents, and the risk of developing type 2 diabetes (T2D) is 4 times greater for obese children compared with those at normal weight. Diabetes is currently the seventh leading cause of death in the United States, but the disease also significantly increases the likelihood of developing severe coronavirus disease 2019 (COVID-19) complications.

In young individuals in particular, obesity—independent of racial, ethnic, or socioeconomic disparities—increases the risk of COVID-19 mortality.

During a session at the at the 18th annual World Congress Insulin Resistance, Diabetes & Cardiovascular Disease presented by the Metabolic Institute of America, experts outlined the benefits and limitations of pharmacological, surgical, and lifestyle interventions for pediatric patients with obesity.

Both pharmacological and surgical interventions yield the best results in these populations when implemented alongside lifestyle interventions, experts explained. Lifestyle therapy, including diet, physical activity, and behavioral strategies, “needs to serve as the backbone of any sort of treatment that we would deploy in the pediatric population in terms of obesity,” said Aaron Kelly, PhD, a professor of pediatrics at the University of Minnesota.

However, limitations in access to bariatric surgeries and adherence to lifestyle interventions open a window for the potential use of pharmacotherapies in children. When it comes to accessibility of bariatric surgeries, “only a small fraction of adolescents with severe obesity who are medically eligible for surgery actually end up getting it,” Kelly said.

Additional data from 2017 found that 52 hours was the minimum threshold of lifestyle therapy (over the course of 1 year) that demonstrated significant weight loss such that it resulted in mean improvements in select cardiovascular and metabolic risk factors. Kelly argued that although there were clinically relevant reductions in body mass index (BMI) after 52 weeks, “this is a whole heck of a lot of hours, a lot of time and resources…The dose of [lifestyle therapy] needed is probably impractical for most families.”

Factors such as attrition and referral rates contribute to low adherence to weight management services among pediatric populations. According to Kelly, analyses found that fewer than 50% of pediatric patients referred by their medical provider to these services end up enrolling in treatment. Access barriers to these programs and limitations on family time and resources may impede enrollment rates. In addition, the dropout rates in many of these clinical programs exceed 50%, Kelly explained.

“Most of the youth that seek specialty weight management care fall into the category of severe obesity; they have very high levels of BMI. And really, we need to set our bar higher and we need to be achieving reductions in BMI and significant reductions at that,” Kelly said.

Outlining the biological aspects of obesity and the body’s response to weight loss, Kelly explained that “humans face an uphill battle, including young humans, adolescents and children, to fight against their underlying biology that is really set up to achieve a high body weight and maintain that body weight almost at all costs.”

Pharmacotherapy and antiobesity medication can help address some of the hormonal changes and drives in the body that urge individuals to put weight back on, Kelly said. Currently in the United States, metformin (a T2D drug) and orlistat are sometimes used separately to treat obesity in children and adults. However, studies showed these 2 medications yielded small reductions in excess weight and the clinical significance is unclear. Significant adverse effects of orlistat have led to low uptake among adults and children and the medication is not commonly used.

However, a 1-year-long adolescent trial studying patients taking 3 mg liraglutide found significant reductions in BMI and the returning of BMI to baseline rates after withdrawing of liraglutide. The trial was conducted to submit data to the FDA and European Medicines Association, which are currently reviewing results to determine approval. A similar ongoing trial of semaglutide is expected to release results in 2022. Liraglutide and semaglutide are both glucagon-like peptide-1 receptor agonists. “I do think that in the next 2 to 3 years, there are going to be many more options available to pediatricians who are interested in adding new tools to their armamentarium of treating obesity,” Kelly concluded.

Although rates of surgical intervention for children with obesity are relatively low, Thomas Inge, MD, chief of pediatric surgery at the Children’s Hospital of Colorado, highlighted promising 5-year outcomes of gastric bypass surgery in adolescents compared with adults.

Of the surgical procedures available to obese individuals, “vertical sleeve gastrectomy has really become the dominant operation even as far back as 2014,” Inge said. “And certainly today, I would say that sleeve gastrectomy is the dominant operation in both teens and adults with well over 90% of all procedures being sleeve gastrectomy worldwide for weight loss surgery.” Additional procedures include the Roux-en-Y gastric bypass (gastric bypass) and laparoscopic adjustable gastric banding.

Results from the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) show that sleeve gastrectomy results in a 26% weight loss over 3 years, compared with a 28% weight loss during the same time period in patients who underwent gastric bypass. Inge compared the results of Teen-LABS with results from the Adult-LABS trial, which assessed bariatric surgery outcomes in adults. Both trials were multicenter prospective observational studies.

A total of 161 participants enrolled in Teen-LABS (19 years or younger) underwent gastric bypass compared with 396 LABS participants (aged 25 to 60 years). Overall, the adolescent group exhibited a 26% median weight loss compared with 29% in the adult population.

However, when it comes to remission of comorbidities over time, researchers found:

  • Adults had a remission of diabetes in the 70% range, whereas the teenagers had remission of more than 80% at 1 year.
  • Teenagers maintained this high level of remission of diabetes (86%) at 5 years.
  • By year 5, 53% of adults were still in remission, representing a statistically significant difference.
  • Irrespective of medication use, teenagers had glycemic control 85% of the time compared with 77% for the adults.
  • Although 88% of teens were taking diabetes medication at baseline, 0% were taking medication at 5 years, compared with 26% of adults still taking medication after 5 years,
  • 20% of teens used insulin at baseline compared with 0% at 5 years, whereas 22% of adults used insulin at baseline compared with 4% in 5 years.
  • After 5 years, only 11% of teens took medications for hypertension compared with 33% of adults.

Adverse events reported in the studies included intraabdominal operations within 5 years.

“While the health benefits should be weighed against the risks of adolescent bariatric surgery, I believe that the long-term advantages appear to outweigh the disadvantages when you look at the magnitude of the improvements in health that can be hopefully experienced for a lifetime by reversing these terrible conditions like T2D and high blood pressure in youth,” Inge concluded. Future long-term studies ought to be carried out to better assess durability and other potential late effects of surgery, including nutritional effects.