Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents 12- to < 18 years old with obesity.
When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls — implying that comparison with the once-weekly injection semaglutide would be more informative — the audience applauded.
The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.
The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, told Medscape Medical News.
“Many of them have been struggling for such a long time — both the parents and the kids themselves,” said Weghuber, from the Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”
“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables 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 with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.
The research showed that “there is the combination of lifestyle plus in the future anti-obesity medications that will open up a new chapter” for treating adolescents with obesity, he summarized.
Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh School of Medicine, agreed. “The results are amazing,” said Arslanian in a press release issued by University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
“Mind-Blowing, Awesome“ Results
The session at ObesityWeek® 2022 was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
Kelly led the SCALE TEENS clinical trial 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 the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.
Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.
“These results are mind-blowing,” said Fox, who is associate professor of pediatrics and co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School.
“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.
Next, Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, North Carolina.
Armstrong is a member of the Executive Committee for the American Academy of Pediatrics Section on Obesity and a co-author of the upcoming clinical practice guidelines that are being published, which will also be discussed at ObesityWeek® 2022.
Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Armstrong said.
200 Teens With Obesity, Only 1 With Overweight
Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.
STEP-TEEN enrolled 201 adolescents ages 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.
Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m2, and a mean 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 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).
A 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).
Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.
The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.
However, the incidence of gastrointestinal adverse events was greater with semaglutide than 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“ Coming in Guidelines for Obesity in Teens
Commenting on the upcoming new recommendations for adolescents, Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.
In the lively question and answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP-TEEN was conducted). “What can we learn?” he asked.
“The bottom line is the relationship” and “close communication” between study investigators and patients, Weghuber replied.
“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.
They are, Weghuber replied, and one with liraglutide is already underway.
The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants ages 6 to < 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.
The last words went to Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.
The trial was funded by Novo Nordisk. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Kelly has 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. Published November 2, 2022. Abstract
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