Semaglutide ‘gives hope’ to obese adolescents
Participants at ObesityWeek® 2022. listened with great excitement to the results of the STEP TEENS phase 3 once-weekly SC trial semaglutide 2.4 mg (Wegovy) in adolescents aged 12 to < 18 years with obesity.
When a panelist at the session said that clinical trials of weight-loss drugs for adolescent obesity should henceforth stop using placebo controls — implying that a comparison with a once-weekly injection of semaglutide would be more informative — the audience applauded.
The results were also simultaneously published in New England Journal of Medicine to coincide with the presentation.
The research “gives hope” to obese adolescents, their parents and their doctors, said the trial’s principal investigator, Daniel Weghuber, Ph.D. Medscape Medical News.
“Many of them struggle for so long – both the parents and the children themselves,” said Weghuber, from the Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
“The problem is not a lack of willpower,” he stressed. “It’s a big misunderstanding.”
“This drug [semaglutide] appears to allow people living with obesity to adhere to recommendations that they may have followed for years and years but [still] they are unable to achieve their goal,” he said. It “allows people to achieve their goals.”
Asked about any potential negative impact on normal growth, Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old at 107 kg who has lost 10%, 15%, 20%” of his weight, he said. There was no indication of problems with normal growth or development in the study.
The research showed that “there is a combination of lifestyle plus future anti-obesity drugs that will open a new chapter” for the treatment of adolescent obesity, he summarized.
Senior author of the study, Silva Arslanian, Ph.D. MD, who holds the Chair of Pediatrics at the University of Pittsburgh School of Medicine, agreed with Richard L. Day. “The results are amazing,” Arslanian said in a University of Pittsburgh press release. “For a person who is 5 feet 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to a loss of about 40 pounds.”
“Amazing, great“ The results
Session at ObesityWeek® 2022 was chaired by Dr. Aaron S. Kelly, professor of pediatrics and co-director of the Center for Pediatric obesity Medicine at the University of Minnesota in Minneapolis.
Kelly led SCALE TEENS clinical trials of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 to < 18 years with obesity, which assigned 125 participants to a daily liraglutide injection group and 126 to a placebo group. SCALE TEENS was introduced and released in May 2020, leading to approval liraglutide for obesity in this age group, in December 2020.
Kelly invited two experts who were not involved in the research to provide their comments, starting with Claudia K. Fox, MD, MPH.
“These results are astounding,” said Fox, associate professor of pediatrics and co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School.
“We’re getting closer bariatric surgery results” in these adolescent obesity patients, added Fox, who is a diplomate of the American Board of Obesity Medicine. For 40% of patients to reach normal weight, “that’s huge” and “life-changing,” she said. And quality improvement “I’m great excited,” she commented.
Next, Kelly called Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Living Program, Duke University, Durham, North Carolina.
Armstrong is a member of the American Academy of Pediatrics Obesity Section Executive Committee and a co-author of upcoming clinical practice guidelines that are being published and will also be discussed at ObesityWeek® in 2022
A look at more than 16,000 meeting abstracts shows that “watchful waiting is not effective,” Armstrong said.
200 teenagers with obesity, only 1 overweight
Obesity affects almost one in five children and adolescents worldwide. Chronic disease is associated with shortened life expectancy and a higher risk of developing serious health problems, such as type 2 diabetesheart disease, non-alcohol fatty liver diseases, sleep apnea and certain cancers. Teenagers with obesity are also more likely depressionanxiety, poor self-esteem and other psychological problems.
STEP-TEEN enrolled 201 adolescents aged 12 to < 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.
Only one recruited patient fit the latter category; the rest had obesity.
The majority of patients (62%) were women. They had a mean age of 15.4 years, a mean BMI of 37 kg/m2and an average waist circumference of 110 cm (43 inches).
Patients were randomized 2:1 to receive a once-weekly 2.4 mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus a lifestyle intervention.
Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.
The primary endpoint, mean change in BMI from baseline to week 68, was -16.1% with semaglutide and +0.6% with placebo (estimated difference, -16.7 percentage points; P < .001).
The second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).
The impact of weight on quality of life – total score of the questionnaire for children (IWQOL-Kids), as well as scores for body esteem, family relationships, physical comfort and social life were better in the semaglutide group.
However, the incidence of gastrointestinal side effects was higher with semaglutide than with placebo (62% vs. 42%).
Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).
Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
“Big change“ It comes in the Guidelines for Teenage Obesity
Commenting on the upcoming new recommendations for adolescents, Armstrong noted that “there will be a strong recommendation” for therapy in the new pediatric obesity guidelines. “It’s a big change,” she said.
In the lively question-and-answer session that followed, one clinician wanted to know what explained the study’s very high completion rate during the COVID-19 pandemic (when STEP-TEEN was conducted). “What can we learn?” asked.
“The bottom line is the relationship” and “close communication” between study investigators and patients, Weghuber replied.
“The fast track will probably lead to adolescent approval,” remarked another audience member. He wanted to know if the company planned to test semaglutide in younger children.
They are, Weghuber replied, and one with liraglutide is already underway.
The SCALE KIDS clinical trials liraglutide randomized 78 participants aged 6 to < 12 years to 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary treatment end date of July 7, 2023.
The last words went to Fox. Current results “are really great,” she said, but “thousands of doctors are hesitant” to prescribe drugs to obese adolescents.
The trial was funded by Novo Nordisk. Weghuber reported being a consultant for Novo Nordisk and a member of the Global Expert Panel on Pediatric Obesity for the company. Disclosures for other authors are listed with the article. Kelly reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).
N Engl J Med. Posted on November 2, 2022. Abstract
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