Early Pharmacotherapy a Consideration for Severe Pediatric Obesity

Pediatric obesity is increasing in prevalence, with severe childhood obesity being seen more and more frequently.

Aaron Kelly, associate professor of pediatrics and medicine at the University of Minnesota Medical School, focused on the dire sequelae of severe obesity in adolescents, and made the case for early medication intervention during a talk at Obesity Week in Boston, MA on November 5, 2014.

Kelly pointed out that adults who had childhood obesity—but who are no longer obese -- are as healthy as adults who never had obesity. This fact, he said, should encourage clinicians to intervene vigorously to help children achieve a healthy body weight. Further, children with severe obesity who are not able to achieve a healthy weight face a host of comorbidities and an uncertain health future.

For example, children with severe obesity are 3-times more likely to have metabolic syndrome than their healthy-weight counterparts, and one in 4 children with severe obesity who seek medical treatment already have glucose intolerance; many will also exhibit some insulin resistance.

When severe obesity is seen in youth, musculoskeletal problems and obstructive sleep apnea are more common, as are psychosocial problems such as depression and an overall lower quality of life. Nonalcoholic fatty liver disease may even occur.

As these children move into adulthood the problems continue. For youth with severe obesity tracked in the Bogalusa heart study, 100% had an adult body mass index (BMI) of at least 30 kg/m2, and 65% had an adult BMI of at least 40 kg/m2. Abnormal kidney function, asthma, diabetes, obstructive sleep apnea, hypertension, lower extremity edema, and severe limitation in ability to walk are all among the midlife comorbidities that are associated with having severe obesity at 18 years of age.

Against this backdrop, Kelly advocated for an intensive and multifaceted approach to achieve effective and durable results in what is really a chronic health issue.

Arguing for consideration of early pharmacotherapy, Kelly cited a large Swedish study showing that lifestyle interventions in an adolescent (14-16 year old) population with overweight or obesity were largely ineffective. In contrast to younger children, for whom these interventions were moderately beneficial, only 2% of the teens were able to achieve a meaningful weight loss.

Bariatric surgery in teenagers can be controversial, but is often effective, producing an overall 30-40% reduction in body mass index (BMI). This effect is seen as long as 2 years after surgery; long term follow-up data collection efforts are ongoing.

Though orlistat is among the agents currently available to treat obesity in youth, Kelly noted that the “mortifying” side effects -- which can include stool leakage — should probably preclude its use in an adolescent population. Metformin, though not FDA-approved for weight loss, can result in a modest BMI reduction of about 3% after one year of use, and may be considered in youth with type 2 diabetes mellitus (T2DM), or even prediabetes. Exenatide, a daily injectable medication to improve glycemic control in T2DM, can also yield a modest reduction in BMI.

There are several newer medications to treat obesity which are not currently approved for use in children or adolescents. Among these, lorcaserin, a novel selective serotonin 2C receptor agonist that can produce a 3-4% weight loss over a year in adults, is expected to be in adolescent safety and efficacy trials by the end of 2015.

The combination of phentermine and topiramate can yield a one-year weight loss of 7-9% in adults, but is not scheduled for adolescent safety and efficacy trials until 2017. The combination of naltrexone and bupropion is on a similar approval schedule for adolescents and can result in a weight loss of 3-4% over one year in adults. Finally, liraglutide, another injectable medication currently used for T2DM that can produce a 5-6% one year weight loss, is expected to be approved soon for adults with obesity. The approval schedule for adolescents is unknown.

Kelly urged clinicians and researchers to continue to advocate for accelerated clinical trial schedules for these medications. Most children and adolescents with obesity will require chronic treatment; currently, predictors of response for particular patients is lacking. Ideally, he added, medications would have beneficial effects on other comorbidities or risk factors as well.