'Mind Blowing' Results in Teen Weight-Loss Trial

SAN DIEGO -- In addition to lifestyle intervention, taking 2.4-mg semaglutide (Wegovy) once a week led to greater reductions in body mass index (BMI) and body weight for adolescents with obesity, a phase IIIa randomized trial showed.

At 68 weeks, the mean change in BMI from baseline was a 16.1% reduction with the glucagon-like peptide-1 (GLP-1) receptor agonist and a 0.6% increase with placebo (P<0.001), reported Daniel Weghuber, MD, of Paracelsus Medical University in Salzburg, Austria, and colleagues.

Furthermore, 73% of participants in the semaglutide group had weight loss of 5% or more compared with 18% of participants in the placebo group (P<0.001); meanwhile, 62% versus 8% respectively had weight loss of 10% or more, and 37% versus 3% had weight loss of 20% or more.

On average, participants on semaglutide lost 15.3 kg (33.7 lb) while those on placebo gained 2.4 kg (5.3 lb) at 68 weeks, according to findings presented at the Obesity Week annual meeting and published simultaneously in the New England Journal of Medicine.

"The degree of body weight reduction is unprecedented," said Weghuber in an interview with MedPage Today. "After years of frustration, all of a sudden patients were actually losing weight. They'd never seen that before."

The results suggest that semaglutide could outperform liraglutide (Saxenda), orlistat (Xenical, Alli), and phentermine-topiramate (Qsymia), the only weight-loss drugs that are currently FDA-approved for use in adolescents ages 12 and up.

Weghuber noted that the weight loss seen in the study was higher in adolescents than in adults who take semaglutide. It's not clear why this happened, he said, but it may have something to do with the drug's ability to suppress the appetite. Adolescents have a higher food drive than adults, he added. "They're more likely to eat and have even more difficulties than adults in resisting not eating."

During a presentation at the meeting, Claudia Fox, MD, MPH, a pediatrician and weight-loss specialist at the University of Minnesota, called the findings "mind-blowing."

"We're really at the doorstep of a new era in terms of how we are now going to be able to effectively treat our adolescent and pediatric patients with obesity," she said, adding that the high level of weight loss in the study is hardly ever seen in adolescents who take other weight-loss drugs. She also noted that adolescents aren't resistant to injectable medication.

Sarah Armstrong, MD, of Duke University in Durham, North Carolina, who spoke during the presentation after learning about the study findings, highlighted the upcoming pediatric guidelines that will recommend that childhood obesity be treated with "the most intensive level of treatment that a child is eligible to receive."

Going forward, she said, "I think we'll see a lot more people interested in these treatment options."

Several other measures improved significantly in the semaglutide group compared with the placebo group, including total cholesterol (-8.3 vs -1.3), VLDL triglycerides (-28.4 vs 2.6), and alanine transaminase levels (-18.3 vs -4.9).

Weghuber pointed out that there were also improvements in weight-related quality of life with semaglutide, which the authors wrote "was not observed in previous trials of phentermine-topiramate or liraglutide in adolescents with obesity."

Fox also highlighted the "dramatic" improvements in quality of life: "That's really what I think kids care about."

The participants who took semaglutide were more likely to have gastrointestinal side effects compared with the placebo group (62% vs 42%), as well as cholelithiasis (4% vs 0%), and serious adverse events (11% vs 9%). Gastrointestinal and gallbladder side effects are common among adults who take semaglutide.

Novo Nordisk, the manufacturer of semaglutide and funder of this trial, is still struggling to provide the drug to patients as a prolonged shortage continues. Many insurers including Medicare refuse to cover the drug for obesity, which costs more than $1,300 a month.

For this multinational double-blind trial, 201 participants ages 12 to 17 with obesity were included and randomized in a 2:1 ratio to semaglutide or placebo. Mean age was 15.4 years, 62% were girls, and more than three-fourths were white. Mean BMI at baseline was 37, and the average body weight was 107.5 kg (235.9 lbs). In addition, 13% had hypertension and 4% had type 2 diabetes.

All participants took part in a lifestyle intervention that included meetings with dietitians, and 134 were assigned to a weekly 2.4-mg subcutaneous dose of semaglutide, while 67 were assigned to placebo.

As for study limitations, Weghuber and colleagues pointed to the high number of female participants, the low proportions of ethnic minorities, and the small number of participants with type 2 diabetes.

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