麻豆传媒

The U.S. Preventive Services Task Force (USPSTF) recommended that children and adolescents with a high body mass index (BMI) be referred to intensive behavioral interventions -- and not weight-loss drugs -- in a final recommendation statement.

Solidifying its previous draft statement, the USPSTF recommended "with moderate certainty" that providing or referring children and adolescents ages 6 years and older with a BMI at or over the 95th percentile for age and sex to comprehensive intensive behavioral interventions "has a moderate net benefit" (grade B recommendation).

"Comprehensive, intensive behavioral interventions with at least 26 contact hours or more that include supervised physical activity sessions for up to 1 year result in weight loss in children and adolescents," the task force wrote in .

Since the draft statement's release in December, the task force has expanded on the harms associated with a high BMI among kids and teens, as well as the use of BMI for screening. While it acknowledged BMI is "an imperfect measure of adiposity," most children at the 95th percentile or higher have high adiposity and therefore should follow the recommended interventions. The focused on screening for childhood obesity, rather than interventions.

The USPSTF kept pharmacotherapy out of the final recommendations at this time -- neither recommending for nor against weight-loss drugs, citing the small number of studies, lack of long-term maintenance data, and potential for side effects. Currently, there are four weight-management drugs approved for adolescents ages 12 and older: semaglutide (Wegovy), liraglutide (Saxenda), phentermine/topiramate (Qsymia), and orlistat (Xenical, Alli).

"If medications need to be used long-term to maintain weight loss, the USPSTF states that long-term studies of both efficacy and harms are essential," wrote Amy S. Shah, MD, of Cincinnati Children's Hospital Medical Center, and colleagues in an accompanying editorial. "This sentiment is undoubtedly shared by the medical community, i.e., the need for additional data to characterize long-term safety, with a focus on outcomes in the years of prime development."

Notably, the American Academy of Pediatrics (AAP) does not share this view, based on its first clinical practice guideline for children and adolescents with overweight and obesity, which included recommendations for weight-loss pharmacotherapy and metabolic surgery in addition to intensive behavioral treatment.

"The differences in between USPSTF and AAP recommendations can be attributed to underlying methodology," Shah and team noted. "The AAP bases recommendations on evidence-based literature and includes expert opinion, clinical guidelines, and position statements from professional societies when necessary. The USPSTF purely uses the evidence-based literature, although USPSTF acknowledges that clinical decisions involve more considerations than evidence alone."

While kids with obesity should start with intensive lifestyle therapy as per the USPSTF recommendations, Shah's group advocated for an individualized approach.

"For many patients, [intensive lifestyle therapy] alone may not be enough to prevent serious outcomes," they wrote. "In these instances, pharmacotherapy and/or bariatric surgery may need to be considered to improve health outcomes in youth with obesity."

While authors of a agreed that there's still "many unanswered questions" about children using weight-loss drugs, they praised the AAP's guidance for considering "the well-documented harms of untreated obesity, the poor access and reimbursement for intensive, comprehensive behavioral treatment, and the FDA approved indications in formulating this recommendation."

"The evidence base related to pharmacotherapy is expected to rapidly grow," noted Thomas N. Robinson, MD, MPH, of Stanford University in Palo Alto, California, and Sarah C. Armstrong, MD, of Duke University in Chapel Hill, North Carolina.

Evidence Report

Underpinning the final USPSTF recommendations was an that included 58 randomized controlled trials with 10,143 participants: 50 trials on behavioral interventions and eight on pharmacotherapy.

All four medications yielded BMI reductions, with the greatest reduction seen with semaglutide (mean difference in BMI -6.0). GLP-1 receptor agonists (semaglutide, liraglutide) and phentermine/topiramate yielded larger weight reductions than behavioral interventions (~8.8 to 39.7 lb), reported Elizabeth A. O'Connor, PhD, of Kaiser Permanente Northwest in Portland, Oregon, and colleagues.

Phentermine/topiramate at the higher dose level was the only medication to demonstrate a clear blood pressure benefit (mean difference in diastolic blood pressure -4.0). Semaglutide improved low-density lipoprotein cholesterol levels (mean difference in percent change -7.1,) and phentermine/topiramate improved high-density lipoprotein cholesterol levels (mean difference in percent change 8.8).

Although serious adverse effects (AEs) were rare for all medications, gastrointestinal AEs were common with GLP-1 receptor agonists and orlistat. In the liraglutide trial, 10.4% discontinued due to AEs.

When evidence was available on weight maintenance after discontinuation, weight rebounded quickly after medication use ended, O'Connor and team concluded. "This suggests that long-term use is required for weight maintenance and underscores the need for evidence about potential harms from long-term use."

Only semaglutide and high-contact behavioral interventions were linked with a boost in quality of life (a 3.7- to 5.3-point increase on mostly 100-point scales), though only a few trials reported on this outcome.

While the AAP guidelines recommended that clinicians refer eligible patients to bariatric surgery, the USPSTF's evidence report did not include any mention of surgery.