Experts Pen Road Map for Drugs to Treat Adolescent Obesity

Marlene Busko

February 07, 2019

Twelve experts in pediatric obesity medicine have identified an urgent knowledge gap for initiating pharmacotherapy in obese adolescents, and so consequently have developed a "clinical road map" to guide other specialists in this field.

The opinion piece was recently published online in Obesity.

"There is an emerging population of adolescents 'stuck' in between lifestyle modification therapy and bariatric surgery for which obesity pharmacotherapy may be helpful," lead author Gitanjali Srivastava, MD, of Boston Medical Center and Boston University School of Medicine, Massachusetts, said in a statement by her institution.

"We hope this opinion piece on pediatric obesity pharmacotherapy will be followed by more clinical trial data, specialized pediatric obesity medicine training programs, the development of protocols and screening tools, and ultimately formal recommendations on the clinical use of medications to treat pediatric obesity," she emphasized.

Approved and Off-Label Drugs to Treat Obesity in Teens

Currently 18.5% of youth are obese and 9.5% are severely obese, the position paper authors write.

There are now six medications that have been approved by the US Food and Drug Administration (FDA) to treat obesity in adults age 18 years and older: orlistat, phentermine, phentermine/topiramate extended release (ER), lorcaserin, bupropion sustained release (SR)/naltrexone SR, and liraglutide.

However, only orlistat and phentermine are approved to treat obesity in adolescents.

"Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population," the authors write, "we offer practical considerations regarding the responsible use of obesity medications by trained pediatric obesity medicine specialists...taking into account existing evidence (unfortunately, currently limited), legal ramifications, and pertinent prescriber- and prescribing-related concerns."

They classify medications for into four categories: medications approved by the FDA for use in obesity in children; those approved by the FDA (whether for obesity or related indications) that have pediatric data; those with no pediatric data; and those pending FDA approval.

Orlistat is approved to treat patients age 12 and older who are obese, and in one meta-analysis, teens with an average body mass index (BMI) of 37 kg/m2 had weight changes ranging from a gain of 1 pound to a loss of 12 pounds; however, gastric side effects such as abdominal cramps and fecal incontinence were common. Orlistat is also available over the counter, Srivastava and colleagues note.

Phentermine has been approved since 1959 for short-term use (generally interpreted as 12 weeks) in obese patients older than age 16 years. In a small review, there was a 4% reduction in BMI with 15 mg/day phentermine plus lifestyle changes versus lifestyle changes alone; side effects included a higher heart rate.

Drugs that are not FDA-approved for obesity but are being used off-label include metformin, licensed by the FDA for type 2 diabetes in those aged ≥ 10 years.

Although topiramate is licensed for use in children aged 2 years and older for epilepsy and those aged 12 years and older for migraine, there are minimal data on its use for weight loss in children.  

There are also minimal data on use of GLP-1 agonists in children with obesity, such as exenatide (approved for type 2 diabetes in adults) and liraglutide (approved for both type 2 diabetes and obesity in adults). "Older generic analogs such as exenatide are more likely to be covered [by insurance] in some states for adolescents with type 2 diabetes mellitus," they observe.

Meanwhile, they note that lisdexamfetamine is FDA approved for attention deficit hyperactivity disorder (ADHD) in children 6 years and older as well as adults, and binge eating disorder in adults. "It is not FDA indicated for weight-loss treatment in either children or adults."

The authors do not recommend off-label use of lisdexamfetamine at this time, but observe that "it may be a beneficial option in younger children ≥ 6 years of age with ADHD and binge eating disorder."

Drugs that are used to treat obesity in adults but lack any trial results in adolescents include lorcaserin and bupropion/naltrexone, although the authors note that "naltrexone and bupropion monotherapy have been used" for indications other than obesity in children.

Lastly, a new drug, setmelanotide, is pending FDA approval for a rare form of monogenetic obesity in adults and children.

Starting and Stopping Anti-Obesity Drugs in Teens

The authors present several criteria for initiating and discontinuing pharmacotherapy for obesity in adolescents.

They stress that drug treatment for obesity in teens should currently be used "only by well-trained experts in a team interdisciplinary environment with conscious monitoring."

Patients and their parents should be informed about off-label use, potential side effects, and risks and benefits among other things.

"It is understood that healthy behaviors and lifestyle modification be continued in conjunction with pharmacotherapy or [metabolic and bariatric surgery]," the authors note.

To be considered for pharmacotherapy for obesity, adolescents should have a BMI ≥ 95th percentile (or ≥ 30 kg/m2) with at least one obesity-related comorbidity or a BMI ≥ 120% of 95th percentile (or > 35 kg/m2) with/without comorbidity, and there is no upper limit for BMI.

Patients should meet the criteria for undergoing bariatric surgery, although the surgery may not currently be appropriate.

And patients should be closely monitored for treatment adherence and possible adverse events.

If there is ≥ 5% BMI reduction from baseline at 12 weeks on the optimal dose or weight gain is slowed, patients should continue taking the medication.

But medication should be discontinued if there are dangerous side effects or the patient does not tolerate it despite dose adjustment.

Srivastava and colleagues also stress the importance of preventing childhood obesity in the first place. "Though we outline the difficulty in the treatment of pediatric obesity once the diagnosis has been established, preventive measures to combat obesity cannot be understated," they write.  

The study was funded by grants from the National Institutes of Health. Srivastava has served as a consultant for Johnson & Johnson. Apovian has reported receiving grants from Aspire Bariatrics, Myos, Vela Foundation, Dr Robert C. and Veronica Atkins Foundation, Coherence Lab, Energesis, and PCORI; grants and personal fees from Orexigen, GI Dynamics, and Takeda; personal fees from Nutrisystem, Zafgen, Sanofi-Aventis, Novo Nordisk, Scientific Intake, Xeno Biosciences, Rhythm Pharmaceuticals, Eisai, EnteroMedics, and Bariatrix Nutrition; and other support from Science-Smart outside the submitted work. Disclosures for the other authors are listed in the article.

Obesity. Published online January 24, 2019. Article

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