Pharmacology: Pediatric Obesity 2017

Of 12-year-olds with BMI at 99th percentile, all will grow up to have BMIs greater than 30, 88% will have BMIs greater than 35, and 2/3 will have class 3 obesity, according to the Bogalusa Heart Study.

Severe obesity is defined as BMI greater than 1.2 times the 95th percentile.

Only 2% of teenagers with severe obesity demonstrated clinically significant BMI reduction with lifestyle modification therapy.

In a study comparing inpatient (6 months) versus outpatient lifestyle modification therapy followed for 2 years, there was no statistically significant difference in outcomes at 2 years despite better response during inpatient treatment.

Mutations in the melanocortin 4 receptor (MC4R) account for the most common single gene mutation causing early onset severe obesity in pediatrics.

Bupropion-naltrexone combination works by bupropion stimulating POMC cells to secrete alpha-MSH (which stimulates MC4 receptors to decrease hunger), while naltrexone blocks the auto-inhibitory feedback from beta-endorphin, allowing relatively more alpha-MSH activity.

When people lose weight, they experience increased hunger, decreased satiety, increased preference for highly palatable foods, and increased metabolic efficiency—all promoting weight regain.

Bariatric surgery is currently the most effective and durable treatment for severe obesity in adolescents.

Orlistat is a lipase inhibitor that blocks absorption of about 30% of fat, is FDA approved for children 12 and older, and in the largest RCT of about 500 patients showed placebo-subtracted BMI difference of about 0.8 units at one year.

Phentermine is FDA approved for age 16 and older (from 1950s approval), but there have been no RCTs in adolescents longer than 1 month duration.

Among adults, phentermine produces mean weight loss of about 3.5 kg.

In studies of adults on phentermine, there have been no withdrawal symptoms upon abruptly stopping and no reports of increased blood pressure, probably because patients are losing weight.

In a chart review of 25 patients on phentermine only for 6 months plus lifestyle modification, compared to 274 receiving only lifestyle modification, there was about a 4% decrease in BMI favoring the phentermine group.

After many studies of metformin, we can expect about a one unit decrease in BMI.

Liraglutide, a GLP-1 agonist, has recently been FDA approved for obesity in adults.

In a pilot study of exenatide (GLP-1 agonist) with about 25 patients, during the first 3 months double-blinded portion, there was a placebo-subtracted effect of about 3% in BMI favoring the exenatide group.

In a chart review of patients taking topiramate only (no other medications) with lifestyle modification therapy, there was about a 6% decrease in BMI at 6 months.

In an RCT of topiramate 75mg/day after meal replacement induction phase, there was no statistically significant effect between topiramate and placebo groups by study end.

Topiramate is FDA approved down to age 2 for seizures and has been used in pediatrics for decades.

Topiramate at 75mg/day was safe in adolescents, with extensive neurocognitive testing showing no signal of cognitive deficits.

Early success in weight management predicts long-term weight loss success, according to adult literature.

Obesity is a chronic disease requiring indefinite medication treatment; stopping the medication results in weight regain, similar to stopping antihypertensive medication causing blood pressure to rise.

Recently FDA-approved medications for adult obesity (age 18+) include topiramate-phentermine combination, liraglutide, naltrexone-bupropion combination, and lorcaserin, approved for BMI >30 or >27 with weight-related comorbidities.

Bariatric surgery is seen as more acceptable than pharmacotherapy for pediatric obesity, despite being arguably riskier and irreversible.