Pharmacotherapy for Adolescent Obesity
Although the obesity rate in American adolescents is over 20% in 12- to 19-year-olds, availability and accessibility of effective treatments remain low. Recent attention has focused on the indications for and use of drug therapy in adolescents. However, only two drugs have received FDA approval for treating adolescent obesity, and bariatric surgery is still not widely used for this age group. Until recently, there has been a lack of data regarding the safety and efficacy of using adult obesity medications in an adolescent population, but this may be changing.
A recent study in the New England Journal of Medicine compared a combination of liraglutide and lifestyle therapy to a combination of a placebo and lifestyle therapy for 56 weeks in a randomized controlled trial of 12- to 17-year-olds. The results were mixed: the treatment group was more likely to experience clinically significant weight loss than the group that received lifestyle therapy alone. Gastrointestinal events occurred significantly more frequently in the liraglutide group, and 13 subjects in the liraglutide group withdrew from the study. As expected, weight regain occurred after the liraglutide was discontinued. Weight losses were similar to those in adult studies. However, in contrast to adult studies, no significant changes occurred in cardiometabolic or quality of life measures compared to the placebo group. One of the greatest concerns was that 3 suicide-related events, including a completed suicide in the liraglutide group, occurred among study participants during the study and the follow-up period. The study authors rightfully emphasized the vulnerability of adolescents with obesity, particularly those with depression.
If liraglutide achieves FDA-approval for obesity treatment in adolescents, it will join orlistat and phentermine as drugs that can be used to treat adolescent obesity. Orlistat, a drug that inhibits the absorption of dietary fat, has been approved for pediatric use in those over the age of 11 years. In a 54 week multicenter randomized clinical trial of orlistat, 12-16 year old adolescents with obesity treated with orlistat in combination with diet, exercise, and behavior modification were compared to adolescents treated with diet, exercise, and behavior modification only. Like liraglutide, this drug led to significant weight loss, but it also caused unpleasant gastrointestinal side effects that could limit its use for this age group.
Phentermine is also an FDA-approved drug for use in adolescents but is limited to those over the age of 16 years. In a small retrospective chart review of phentermine therapy, 25 adolescents with severe obesity treated with phentermine and lifestyle modification for three months were compared to adolescents treated with lifestyle modification only. Forty percent of those taking phentermine lost >5% of their body weight at three months and at six months over 60% had lost >5% of their body weight. These results compare favorably with weight loss associated with liraglutide and indicate that a large and longer placebo controlled randomized trial of phentermine is long overdue. One important caution is that phentermine is chemically related to amphetamines and its use in adolescents must be monitored for abuse or dependence.
One of the most frequent drugs used off-label is metformin. A six month randomized double-blind placebo-controlled trial of metformin studied 6-12 year old children with severe obesity. Both metformin- and placebo-treated children received a weight reduction lifestyle modification program. Investigators found a modest decrease in BMI in the metformin treated group. Gastrointestinal side effects that limited achieving a maximal dose of metformin occurred in 17% of subjects.
An important question raised by these studies is how much weight loss is enough to reduce weight related co-morbidities or reduce the likelihood of persistence into adulthood. A 5% weight loss in adults with obesity reduces many of the co-morbidities associated with adult obesity. As the table below indicates, only phentermine achieved >5% weight loss in more than half of the patients treated. Furthermore, no significant difference was found for any of the biometric or quality of life indictors in the liraglutide-treated group of adolescents, and the longer-term effects on the persistence of obesity have not been studied for any of these drugs. It seems to me that the ideal drug for the treatment of childhood obesity should prevent obesity persisting into adulthood and reduce obesity-associated co-morbidities. These studies emphasize that we have a long way to go.
Although there are a few effective obesity treatment tools for adolescents, these patients deserve a full range of treatment options. Never has successful prevention and treatment of childhood obesity been more pressing than it is now in the midst of a pandemic that includes obesity and obesity-related diseases as risk factors for severe illness. Experts have suggested that lockdowns and school closures across the country may lead to a surge in pediatric obesity and anecdotal evidence from Europe suggests that obesity plays a large role in the hospitalization and clinical course of young people with COVID-19. More than ever it is evident that pediatric obesity is a complex disease that requires well-researched, evidence-based treatments. Failing to address obesity in America’s youth puts the country at risk of higher morbidity and mortality, both from chronic and infectious diseases.