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Half of obese teens on Wegovy return to normal weight – STEP TEENS trial

In what researchers describe as unprecedented, the drug Wegovy (semaglutide) reduced the weight of nearly 50% of teenagers “to a level below what is defined as clinical obesity …historically unprecedented with treatments other than bariatric surgery”.

Far more teens with obesity treated with 2.4 mg semaglutide returned to normal weight or dropped below the obesity threshold compared with placebo-treated patients, the secondary analysis of the phase IIIa STEP TEENS trial found.

MedPage Today reports that during the 68-week trial, 44.9% of teens with obesity returned to either normal weight or went down to the overweight category while on treatment, compared with only 12.1% of those on placebo (OR 22.7, 95% CI 7.6-67.9), according to Aaron Kelly, PhD, of the University of Minnesota Medical School in Minneapolis, and colleagues.

And by the end of the trial, about 25% versus 2%, respectively, dropped to normal weight status, according to findings presented at last week’s annual European Congress on Obesity in Dublin and simultaneously published in Obesity.

“These results underscore the high degree of clinical effectiveness of semaglutide in adolescents with obesity,” said Kelly.

“If an adolescent has medical indications for an anti-obesity medication, I believe healthcare providers should offer that as part of the comprehensive treatment approach. But it's not just one thing…. It’s lifestyle therapy, which was included in this trial, it’s the use of anti-obesity medications if indicated, and even for some, metabolic and bariatric surgery.”

At the start of the trial, teens on the glucagon-like peptide-1 (GLP-1) receptor agonist were generally split between the three obesity classes: class I (n=69; 31.6% of participants), class II (n=69; 33.1%), class III (n=62; 35.3%).

By the end of the trial:

• 25.4% of semaglutide-treated participants were normal weight
• 19.5% were overweight
• 22% had class I obesity
• 19.5% had class II obesity
• 13.6% had class III obesity

On the other hand, the proportion of those falling into class III increased for those on placebo (19% to 22.4%), but dropped for obesity classes I (39.7% to 32.8%) and II (41.4% to 32.8%). Only 10.3% of those on placebo achieved overweight and 1.7% achieved normal weight.

Obesity classes were defined by the CDC body mass index (BMI) growth charts:

• Class I: BMI in the ≥95th to <120% of the 95th percentile
• Class II: BMI ≥120% to <140% of the 95th percentile
• Class III: BMI ≥140% of the 95th percentile

There were also 23.5-higher odds of teens improving at least one BMI category with semaglutide versus placebo (OR 23.5, 95% CI 9.9-55.5, P<0.0001), seen in 73.7% of treated patients versus 19% of placebo patients. A total of 44.9% of teens on semaglutide improved two or more BMI categories versus only 3.4% of those on placebo.

These findings build on the pivotal findings of the STEP Teens trial, presented at the 2022 Obesity Week annual meeting and published in the New England Journal of Medicine.

Here, the mean change in BMI from baseline was a 16.1% reduction with semaglutide compared with a 0.6% increase with placebo (P<0.001) at week 68. On average, participants on semaglutide lost 15.3 kg (33.7 lb), while those on placebo gained 2.4 kg (5.3 lb).

“The degree of body weight reduction is unprecedented,” lead study author Dr Daniel Weghuber of Paracelsus Medical University in Salzburg, Austria, told MedPage Today.

“After years of frustration, all of a sudden patients were actually losing weight. They’d never seen that before.”

Although the study wasn’t designed to test sex differences, the BMI treatment differences were numerically – but not statistically – greater in females than males. The same was true for patients aged 12 to 15 compared with those 15 to 18. Only patients with obesity were included in this post-hoc analysis.

The average age was 15.5, more than 60% of participants were female, and most were at Tanner stage five. More than 80% had normoglycaemia. Semaglutide was added to lifestyle intervention, comprising healthy nutrition counselling and a goal of 60 minutes of moderate- to high-intensity physical activity daily.

Said Kelly: “This is not going to solve the obesity problem, but it’s an important piece to the puzzle in helping to solve it, especially for those who already have obesity.”

Study details

Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg

Aaron Kelly, Silva Arslanian, Dan Hesse, Aske Thorn Iversen, Antje Körner, Signe Schmidt, Rasmus Sørrig, Daniel Weghuber, Ania Jastreboff

Published in Obesity on 17 May 2023.


To examine how improvement in body mass index (BMI) with the glucagon-like peptide-1 receptor agonist, semaglutide, translated to changes in BMI category in a post-hoc analysis of the double-blind, phase 3a randomised controlled STEP TEENS trial (NCT04102189).

Adolescents with obesity received once-weekly subcutaneous semaglutide 2.4 mg or placebo, plus lifestyle intervention which comprised counseling in healthy nutrition and a goal of 60 minutes of moderate- to high-intensity physical activity per day. Achievement of an improvement in BMI category and attainment of normal weight or overweight BMI category by week 68 were analysed using logistic regression models.

In the overall population, 44.9% of participants receiving semaglutide achieved normal weight or overweight BMI category versus 12.1% receiving placebo at week 68 (odds ratio: 22.7; 95% confidence interval [CI]: 7.6–67.9). The proportion of semaglutide-treated participants in obesity class III decreased from 37.3% to 13.6%, but increased with placebo. The odds ratio for achieving an improvement of ≥1 BMI category was significantly greater with semaglutide versus placebo (23.5; 95% CI: 9.9–55.5); an improvement of ≥1 BMI category was seen in 73.7% of participants receiving semaglutide compared with 19.0% with placebo. Conclusions Semaglutide was highly effective in reducing BMI category. While on treatment, most trial participants' BMI improved by ≥1 category and > 40% reached a category below the obesity threshold.

Study 2 details

Once-weekly semaglutide in adolescents with obesity

Daniel Weghuber, Timothy Barrett, Inge Gies, Aaron Kelly, et al for the STEP TEENS Investigators*

Published in New England Journal of Medicine on 15 December 2022


A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking.

In this double-blind, parallel-group, randomised, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68.

A total of 201 participants underwent randomisation, and 180 (90%) completed treatment. All but one of the participants had obesity. The 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; 95% confidence interval [CI], −20.3 to −13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group.

Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone.


Obesity article – Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg (Open access)


NEJM article – Once-weekly semaglutide in adolescents with obesity (Open access)


MedPage Today article – Quarter of Wegovy-treated teens with obesity return to normal weight (Open access)


See more from MedicalBrief archives:


WHO warning about weight-loss drugs as obesity guidelines amended


Concern as social media fuels global weight loss drug fad


Maintenance semaglutide injections led to continued weight loss — STEP 4


STEP 2 trial: Semaglutide hope for patients with type 2 diabetes







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