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Lifechanging new drug helped half of teens drop below the clinical cut-off for obesity

[May 24, 2023: Chanel Carrington, The Obesity Society]

Researchers have developed a small-molecule drug that prevents weight gain and adverse liver changes. (CREDIT: Getty Images)

A new secondary analysis of the STEP TEENS trial published in the journal Obesity shows that almost half (45%) of the adolescents assigned to semaglutide in the trial managed to lose enough weight to drop below the clinical cutoff for obesity.

The study, led by Aaron S. Kelly, PhD, co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis, and colleagues, also showed almost three quarters (74%) moved down by at least one weight category.


The full STEP TEENS trial, published in 2022 in the New England Journal of Medicine (NEJM), showed the efficacy of semaglutide in helping adolescents lose weight. In this secondary analysis of the STEP TEENS trial, the authors examined the effect of semaglutide treatment on improvement in body mass index (BMI) categories.

Adolescents aged 12 to under 18 years with BMI in the highest 5% were included in this analysis. Participants were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg (n=134) or placebo (n=67) for 68 weeks; both groups received matching lifestyle counseling. The proportion of participants who achieved an improvement in BMI category from baseline to week 68 was assessed using on-treatment data.


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BMI categories, based on Centers for Disease Control and Prevention BMI charts, were: normal weight (BMI ≥5th to <85th percentile); overweight (BMI ≥85th to <95th percentile); and obesity class I (OCI; BMI ≥95th percentile). Severe obesity class II (OCII) and class III (OCIII) are based on a percentage above the 95th percentile cutoff for obesity – OCII is defined as ≥20% above this cutoff and OCIII is defined as ≥40% above this cutoff.

Of 201 adolescents randomized, 62 (31%), 69 (34%) and 69 (34%) were in OCIII, OCII and OCI, respectively; only one participant (0.5%) had overweight and was excluded from this secondary analysis. At randomization, mean body weight was 107.5 kg and mean BMI was 37.0 kg/m2 (OCII).


At week 68, 74% of participants on semaglutide had an improvement of one or more BMI categories versus 19% on placebo. An improvement of ≥2 BMI categories occurred in 45% of participants treated with semaglutide versus 3% with placebo. Overall, treatment with semaglutide reduced the proportion of participants with the most severe degree of obesity (OCIII) from 37% to 14% after 68 weeks.

By week 68, a total of 45% participants in the semaglutide arm experienced a reduction in BMI below the clinical cutoff point for obesity (i.e., reached normal weight or overweight) versus 12% of participants in the placebo arm.


The authors concluded, “Once-weekly semaglutide was associated with clinically meaningful improvements in BMI categories versus PBO across all BMI classes in adolescents with obesity.”

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. (CREDIT: New England Journal of Medicine)

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


The researchers discovered the drug by first exploring how magnesium impacts metabolism, which is the production and consumption of energy in cells.

Magnesium is the fourth most abundant element in the body after calcium, potassium, and sodium, and plays many key roles in good health, including regulating blood sugar and blood pressure and building bones. However, the researchers found that too much magnesium slows energy production in mitochondria, which are cells’ power plants.

“Lowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress,” said co-lead author Manigandan Venkatesan, PhD, postdoctoral fellow in the Muniswamy lab.


For more science and technology stories check out our New Discoveries section at The Brighter Side of News.


Note: Materials provided above by The Obesity Society. Content may be edited for style and length.


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