US Pharm. 2015;40(5):35-38.
ABSTRACT: The etiology of adolescent obesity relates to both genetic makeup and environmental factors such as increased consumption of high-energy foods and decreased physical activity. Prevention of obesity during childhood is supported by numerous philanthropic efforts in the United States; however, primary preventive measures often are not implemented appropriately, resulting in adolescent obesity. Secondary and tertiary prevention strategies facilitated by a multidisciplinary healthcare team incorporate structured behavioral interventions to prevent adult obesity. Beyond nonpharmacologic therapies, evidence supports the use of pharmacologic agents and surgical procedures for adolescent obesity management in certain populations.
According to the CDC, approximately 12.7 million children and adolescents in the United States are obese, totaling 17% of the population aged 2 to 19 years.1 As with adult obesity, risk factors for childhood obesity include race, age, and social class.2-4 In addition, parental factors such as education level and income have been noted to impact the prevalence of childhood obesity. Complications secondary to adolescent obesity, including hypertension, dyslipidemia, and type 2 diabetes mellitus (T2DM), align with those of adult obesity; however, these complications may yield higher mortality outcomes, owing to the younger age at onset and the limited use of pharmacologic and surgical methods in this population.5 This review article aims to summarize the etiology, diagnosis, prevention, and treatment of adolescent obesity.
The cause of adolescent obesity is regarded as multifaceted, given the numerous components that increase a child’s risk of developing the condition. First, there is a known genetic link, as described in a study of twins with heritability estimates between 0.5 and 0.9.6 Accounting for a much larger proportion of cases is the number of environmental factors in the adolescent’s home. In one report, children aged <3 years being raised by obese parent(s) were more likely to become obese, which reflects an environmental, not genetic, etiology.7 Additionally, variables outside the home—e.g., increased availability of high-energy foods and sugar-filled beverages at school, minimal advertising of healthful foods, lack of required physical activity at school, larger portion sizes, and more time looking at screens—have contributed to the current rates of adolescent obesity in the U.S.8-16 These factors can present challenges for any child regardless of social status, but children of low-income families often face further barriers to achieving a healthy lifestyle, including the lack of safe areas for physical activity and the expense of healthful food choices.14,17
The diagnosis of obesity in the adolescent population is determined by BMI.5 In children aged 2 to 18 years, cutoff BMI points of ≥95th percentile and ≥99th percentile per adolescent age correspond to obesity and severe obesity, respectively. Because measurements of weight and height are easily obtainable, most healthcare providers should feel proficient in assessing for adolescent obesity. Beyond diagnosis, depending upon the severity of the obesity, behavioral, pharmacologic, and surgical interventions may be necessary from numerous supporters, including healthcare providers.
For this review, a systematic search was conducted via PubMed to identify literature reports relating to obesity in the adolescent population. Medical Subject Headings (MeSH) included “obesity,” “adolescent,” “pediatric,” and “child.” Initial results were limited to clinical trials from 2004 to the present that were conducted in human subjects and written in English. Applicable guidelines and further relevant trials were identified from the initial retrieved primary literature search.
Nonpharmacologic Prevention and Treatment
The importance of preventing adolescent obesity through lifestyle modification is well documented and supported by billions of dollars of research in the U.S. Many health-focused philanthropies, such as the Robert Wood Johnson Foundation, develop and maintain programs to slow or reverse progression of overweight or obesity in childhood.18 Behaviors that increase the risk of obesity are often easily identified, but persuading the whole family to change these behaviors remains a challenge, given that the promotion of excess energy consumption is ubiquitous in today’s society.19
The Academy of Nutrition and Dietetics (A.N.D.) classifies pediatric overweight and obesity prevention into primary, secondary, and tertiary strategies. Primary prevention measures are designed to prevent adolescent obesity, and secondary and tertiary prevention measures are designed to prevent progression of adolescent obesity to adult obesity.20 Primary prevention incorporates a lifestyle or system-level approach for all adolescents, regardless of weight. In this strategy, the adolescent’s environment is evaluated for possible attributing risk factors, and programs on general topics such as healthy eating and physical activity are promoted. These interventions are generally widespread and available to the entire population via family-, school-, and community-based programs. The Expert Committee recommendations report regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity endorses the application of motivational interviewing or the stages of change theory, which takes into account the individual’s readiness to change.5 This strategy also allows the provider to assess the willingness and understanding of the adolescent and his or her family and to provide incentives.5,21,22 The A.N.D. endorses incorporation of both physical activity and nutritional interventions, since the combination of measures has been proven effective in improving adolescent adiposity, whereas using a single intervention is less beneficial.20
The secondary prevention strategy centers on the overweight or obese adolescent as an individual, and incorporates a structured interventional method of change.20 In the tertiary prevention stage, which is the most intensive strategy, management of overweight or obesity with pharmacologic therapies or bariatric surgical procedures may be considered. A multidisciplinary intervention team, including a provider and a dietitian or clinician who can provide nutritional education, should be implemented in the secondary and tertiary prevention stages. No matter which prevention strategy is indicated, participation of the adolescent and anyone who has an influence on the adolescent’s behavior via multifaceted behavioral modification measures is recommended.
Several pharmacologic agents are FDA-approved for weight management. Orlistat, a lipase inhibitor that directly affects fat absorption, is the only pharmacologic agent approved for the treatment of obesity in the adolescent population.23 Specifically, the 120-mg prescription strength is approved, not the OTC formulation, owing to the need for provider monitoring.
Chanoine and colleagues conducted the largest study detailing the benefit and tolerability of orlistat in an adolescent population also receiving dietary and exercise counseling.24 The adolescents, with a mean age of 13 years and a BMI of 35.4 kg/m2, were randomized to receive orlistat 120 mg three times daily with meals or placebo for 52 weeks. Significant improvements in body weight (BW), waist circumference, BMI, and diastolic blood pressure were seen in adolescents taking orlistat versus those given placebo. Additionally, significantly more adolescents taking orlistat achieved at least 5% and 10% total BW reduction—which coincides with T2DM risk reduction occurrence in an adult population—compared with placebo (19% and 11%, respectively, P = .03; 9.5% and 3.3%, respectively, P = .01).25 Adverse effects (AEs) associated with orlistat therapy, mostly gastrointestinal (GI), were consistent with phase III studies conducted in adults; however, these AEs occurred more often in adolescents than in subjects in manufacturer reports. The greater risk of GI AEs in adolescents compared with adults could be related to greater receptiveness and adherence to recommended dietary modifications on the part of adults. Discontinuation of therapy because of an AE was greater in the placebo group than in the orlistat group. To date, there is no literature regarding use of orlistat beyond 1 year in adolescents; however, data in adults demonstrate safety with long-term use.
Five glucagon-like peptide-1 (GLP-1) agonists are FDA-approved for management of T2DM in adults; one of these, liraglutide, is also approved for weight management.23 Based on their efficacy and relative tolerability, GLP-1 agonists have been proposed as a viable pharmacologic agent for weight management in adolescents. The longest trial evaluating the use of GLP-1 agonist therapy in obese adolescents, a crossover pilot study conducted by Kelly and colleagues, investigated the safety and efficacy of exenatide titrated to 10 mcg twice daily over 6 months in 11 adolescents (mean age 12 years and BMI 36.7 kg/m2).26 BMI, BW, insulin, and beta-cell function were significantly improved in the exenatide group versus controls (–0.9 vs. 0.84 kg/m2, P = .01; –0.99 vs. 2.97 kg, P = .017; –1.62 vs. 6 mU/L, P = .017; 14.5 vs. –1.16, P = .034, respectively). All AEs were considered mild, and the AE most commonly reported was nausea, followed by vomiting and headache. Further research is needed prior to approval of GLP-1 agonists to manage adolescent obesity; however, there is currently no evidence to suggest that the tolerability, pharmacology, and pharmacokinetics of exenatide in adolescents differ from those in adults.
There is little primary literature evaluating the use of other weight-management medications approved by the FDA for use in adults, such as phentermine, phentermine plus topiramate, bupropion plus naltrexone, and lorcaserin. A study of the use of topiramate for reducing migraine occurrence in adolescents (mean age 14 years) revealed an approximate rate of AEs of 30%, with cognitive decline constituting the majority of AEs.27 Given the AE profile of phentermine-containing products, use is not recommended in adolescents aged <16 years.23 Overall, evidence regarding the pharmacologic weight management of adolescent obesity is limited. Orlistat is the only FDA-approved agent recommended for use in adolescents, and exenatide has shown promise with regard to efficacy; however, more safety data are needed.
For adolescents diagnosed with severe obesity who have failed weight-management interventions despite organized multidisciplinary means or pharmacologic management, bariatric surgery is an option.28,29 The bariatric surgical procedures most commonly performed in obese adolescents are the Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), and vertical sleeve gastrectomy (VSG). RYGB yields the greatest weight loss; however, LAGB is being increasingly performed in adolescents because of its shorter overall hospital stay and operating time.29 Third-party coverage of any type of bariatric surgery in adolescents is rare because the procedures are FDA-approved for use in adults only.30
In 2013, a meta-analysis of 23 trials evaluated the safety and efficacy of RYGB, LABG, VSG, and biliopancreatic diversion in 637 patients with mean ages of 6 to 18 years at enrollment.31 Mean BMI was reduced by 17.2, 10.5, and 14.5 kg/m2 following RYGB, LAGB, and VSG, respectively, 1 year post surgery. Complications were less likely following LAGB compared with RYGB in adolescents; however, LAGB recipients often required additional surgery.
Following publication of the Teen-Longitudinal Assessment of Bariatric Surgery study (the largest trial evaluating the safety of bariatric surgery in adolescents), VSG gained popularity, as it was shown to pose less risk of major postsurgery complications compared with RYGB and LAGB.32
Despite short-term data showing marked weight loss and projected comorbidity improvement with bariatric surgery, the procedures remain a last resort for adolescent obesity management, owing to financial burden, lack of FDA approval, postsurgical AEs, and absence of long-term safety and efficacy data. In addition, behavioral approaches to managing weight have been shown more effective in adolescents compared with adults, which suggests that more invasive procedures, such as bariatric surgery, may not be necessary for the desired weight-loss outcome.7 In summary, the use of bariatric procedures in adolescents with a BMI ≥99th percentile for age has been documented to be relatively safe and effective over the last two decades, and this option may be considered if the adolescent and the family are in agreement.32
Pharmacists in clinical and community practice settings can be instrumental in the management of adolescent obesity. Clinical pharmacists, who frequently are responsible for educating patients about obesity-related comorbidities, such as T2DM and hypertension, should provide nutritional education, as applicable, to both the adolescent and his or her family. Community pharmacists should be prudent when counseling about weight-management medications in order to ensure adherence and thereby maximize benefit achievement, given that the incidence of drug AEs may be greater in adolescents compared with adults. All healthcare providers can be influential in the prevention and management of adolescent obesity. This responsibility extends beyond the pharmacist, and a multidisciplinary team of providers should be involved in order to improve outcomes, mainly the prevention of adult obesity and comorbidity.
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