Pharmacotherapy for the Treatment of Overweight and Obesity in Children, Adolescents, and Young Adults in a Large Health System in the US

Abstract

Lifestyle modifications focused on diet, physical activity, and behavior have a modest impact on weight reduction in children, adolescents, and young adults (YA) with overweight and obesity. Several anti-obesity medications (AOMs) have been approved by the Food and Drug Administration (FDA) for use among adult patients with a body mass index (BMI) ≥27 kg/m 2 and at least one obesity-related illness. However, only two FDA-approved AOMs are available for use in children and adolescents, which leads to the frequent off-label use of adult AOMs among this population. We sought to investigate current prescribing patterns of AOMs from school age through to young adulthood in a large unified health system. Using a centralized clinical data registry containing the health data of ∼6.5 million patients, individuals aged 5-25 years old with overweight and obesity who were taking one of eight commonly prescribed AOMs from 2009 to 2018 were extracted. A total of 1,720 patients were identified, representing 2,210 medication prescribing instances. The cohort was further stratified as children (5-12 years old), adolescents (13-18 years old), and YA (19-25 years old). The mean BMI at the time of medication initiation was 34.0, 39.1, and 39.6 kg/m 2 , respectively, which corresponded to a BMI z-score (BMIz) of 2.4 and 2.3 for children and adolescents, respectively. Metformin was the most commonly prescribed medication across all ages, including off-label use for weight-loss among children and adolescents. The most commonly off-label prescribed AOM among YA was topiramate. Multivariable analyses demonstrated phentermine was the most effective AOM, with a 1.54% total body weight among YA (p = 0.05) and a 0.12 decrease in BMIz among adolescents (p = 0.003) greater final weight loss when compared to the respective overall frequency-weighted means. Our study demonstrates a statistically significant weight loss among adolescents and young adults on select pharmacotherapy. The small magnitude of this effect should Czepiel et al. Pharmacotherapy for Weight Reduction in Pediatrics be interpreted carefully, as it is likely an underestimate in the absence of a true control group. Pharmacotherapy should therefore be considered in conjunction with other multimodal therapies such as lifestyle modification and metabolic and bariatric surgery when treating overweight and obesity.

Gastric Sensory and Motor Functions and Energy Intake in Health and Obesity—Therapeutic Implications

“…There are five FDA-approved medications for long-term obesity care: orlistat, phentermine/topiramate, bupropion/naltrexone, and liraglutide for adults, orlistat and liraglutide for patients ≥12 years of age; and phentermine for adolescents ≥16 years [ 172 , 173 , 174 ]. Table 3 summarizes the effects of anti-obesity medications on gastric emptying in adults.…”

Metformin May Contribute to Inter-individual Variability for Glycemic Responses to Exercise

“…But the effect of prescribing metformin with exercise in children and adolescents have on the rate of gain in these fitness outcomes is largely unknown in boys and girls. With emerging literature suggesting that off label or prophylactic use of metformin may be effective for weight management and obesity prevention in adolescents (54,71,127) more children may be provided metformin and recommended to exercise. This raises potential concern toward altered maturation growth rates and cardiometabolic risk during youth as well as then for later in life health risk compared with youth advised to exercise only with proper nutrition (54,71).…”

Topiramate for Posttraumatic Symptoms in an Obese Adolescent Girl

“…Studies have found significant improvement when topiramate is used as adjunctive therapy for refractory bipolar disorder (Mula et al 2006). A small study found that adjunctive topiramate therapy for bipolar disorder type I/II in the pediatric population led to a 62% improvement (DelBello et al 2002).…”

“…This combination medication has been shown to be safe and effective in adolescents (Hsia et al 2020). Appetite suppression caused by topiramate may be due to activation of the GABA-A receptor as well as antagonism of the kainite/AMPA glutamate receptors that stimulate appetite in the lateral hypothalamus (Arnone 2005;Czepiel et al 2020). Topiramate has also been shown to inhibit fat deposition by modulation of lipoprotein lipase (Richard et al 2000).…”