Half of Teens Drop Below Obesity Cutoff With Semaglutide

Becky McCall

May 18, 2023

DUBLIN — Nearly half (45%) of adolescents assigned to semaglutide (Wegovy), a once-weekly glucagon-like peptide-1 (GLP-1) agonist, managed to lose enough weight to drop below the clinical threshold for obesity, according to a secondary analysis of the STEP TEENS (Semaglutide Treatment Effect in People With Obesity) trial.

By comparison, only 12.1% of adolescents with obesity taking placebo in the trial dropped below the obesity threshold.

The study also found that 74% of participants shifted down by at least one body mass index (BMI) category after receiving the GLP-1 agonist, compared with 19% of those taking placebo.

"In a practical sense, we see that semaglutide reduced weight to a level below what is defined as clinical obesity in nearly 50% of the teens in our trial, which is historically unprecedented with treatments other than bariatric surgery," remarked Aaron Kelly, MD, co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis, who presented the latest data at this year's European Congress on Obesity (ECO).

"There was a 22.7-higher odds of dropping below the obesity threshold if assigned to semaglutide versus odds on placebo [P < .0001], and a 23.5-fold higher odds of dropping BMI by one category if on semaglutide [P < .0001]," he reported.

This analysis follows the 2022 publication of the main results of STEP TEENS published in the New England Journal of Medicine, as reported by Medscape Medical News, which showed semaglutide helped adolescents lose weight. The drug was subsequently approved by the US Food and Drug Administration for the treatment of obesity in those aged 12 and over in January of this year.   

The new analysis was presented at ECO and simultaneously published in Obesity. 

Grace O'Malley, PhD, Child & Adolescent Obesity Service, Children's Health Ireland, Dublin, commented on the findings, noting that adolescents' access to comprehensive healthcare is essential for the proper treatment of obesity. 

"Treatment requires a long-term, multidisciplinary chronic-care approach, and usually, when treatment stops, the biological mechanisms driving the obesity begin again to drive the build-up of adipose tissue," she said. This means that "long-term treatment including nutrition therapy, exercise...behavioral support, and sleep therapy needs to be available to families in combination with pharmacotherapy and surgical intervention where required."

"The results of the STEP TEENS study represent a promising development for the treatment of adolescent obesity and for associated complications related to liver function," she added. "The observed improvements in obesity category and [liver enzyme] alanine transaminase, will help clinicians plan more tailored care for adolescents with obesity," she noted.

Semaglutide Shifts BMI Category

In this new secondary analysis of STEP TEENS, the authors examined the effect of subcutaneous semaglutide 2.4 mg on moving adolescents from one BMI category to another, including dropping below the obesity threshold into the overweight or normal weight categories.

The study also looked at the effect of semaglutide on glucose metabolism and cardiovascular risk factors, as well as safety and tolerability. However, this particular analysis only examined adolescents with obesity (only one person had overweight, and so they were excluded), who were divided into three further subclasses: obesity class I (BMI ≥ 95th to < 20% above the 95th percentile); obesity class II (BMI ≥ 20% to < 40% above 95th percentile); and obesity class III (BMI ≥ 40% above the 95th percentile).

After a 12-week run-in period of lifestyle intervention only, a total of 200 adolescents (12-18 years) with obesity (in the top 5% of BMI) were randomized (2:1) to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, after a 16-week titration period. All participants continued to receive counseling about healthy nutrition and were set a goal of 60 minutes per day of moderate- to high-intensity physical activity.

Kelly and colleagues determined levels of improvement in BMI category and attainment of normal weight, or overweight, BMI category by week 68.

At baseline, the percentage of participants in obesity class I, II, or III, in those taking placebo was 39.7%, 41.4%, and 19.0%, or taking semaglutide was 31.4%, 31.4%, and 37.3%, respectively.

"After 68 weeks not a lot happened [in placebo participants], however, 12.1% of placebo participants did drop below the obesity threshold into overweight or normal-weight categories," reported Kelly.

Referring to participants taking semaglutide, he added that "a total of 45% of patients on semaglutide dropped below the clinical BMI cut point for obesity, such that 19.5% dropped into the overweight category and 25.4% reduced their BMI into the normal-weight category."

Turning to obesity class, Kelly reported that of those initially with obesity class III taking placebo, 91% remained in that class and 9.1% dropped to obesity class II at week 68. For those adolescents with obesity class III taking semaglutide, 36.4% dropped to obesity class II, 18.2% dropped to obesity class I, 11% dropped below the obesity threshold, and 34.1% remained in obesity class III, he added.

For obesity class II specifically, 71% of placebo participants stayed in that category, while 12% moved up a category. "On semaglutide, over 50% [51.2%] reduced their BMI below the obesity cut point," noted Kelly.  

In obesity class I, 26% of patients taking placebo reduced their BMI below the obesity cut point. "On semaglutide, nearly 80% reduced their BMI below the obesity threshold, with 57% dropping their BMI into the normal category," he said.

"When we looked at baseline factors that might predict the response to semaglutide or placebo, we did not find any factors that were...significant due to small sample sizes," he said. However, he pointed out that "females tended to respond better to semaglutide, likewise younger adolescents, and middle body weights tended to respond better to the drug, and there was a similar pattern with obesity classes."

Commenting on the study, Jesse Bittman, MD, University of British Columbia, Vancouver, Canada, said: "Good to see more data on different populations that some semaglutide is used in and the variability in response to it. The focus on BMI was interesting because in obesity medicine we spend a lot of time telling our patients not to focus on BMIs and 'normals' because there are more important tools, and we see that when these become the focus of research outcomes they can become problematic."

Asked by Medscape Medical News whether rapid weight loss in adolescents might be problematic in some respects, Bittman pointed out that "one concern with these medications is whether people are going to have loss of muscle mass or malnutrition, or whether they develop eating disorders and other disturbed eating behaviors," he added. 

Kelly has reported engaging in unpaid consulting and educational activities for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Vivus, and receiving donated drug/placebo from Novo Nordisk and Vivus for National Institutes of Health-funded clinical trials. O'Malley has declared having received grants in the past 3 years from the Health Research Board, Department of Health, Ireland, European Association for the Study of Obesity (via a Novo Nordisk educational grant), Healthy Ireland fund, and the Royal College of Surgeons in Ireland Strategic Academic Recruitment (StAR) Programme. Bittman has reported receiving funding from Novo Nordisk, Bayer, and Bausch Health.

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