High-dose semaglutide triggers weight loss in adolescents with obesity

medwireNews: A weekly injection of a high dose of semaglutide results in substantial weight loss among adolescents with obesity, show the STEP TEENS trial findings.

During 68 weeks of treatment with the glucagon-like peptide (GLP)-1 receptor agonist, the 134 adolescents assigned to receive active treatment reduced their starting BMI by an average of 16.1%.

By contrast, the 67 taking placebo had an average increase of 0.6%, despite all participants receiving lifestyle counselling throughout the trial.

Daniel Weghuber (Paracelsus Medical University, Salzburg, Austria) and co-researchers say that the reduction with semaglutide was “substantially greater” than that achieved with the GLP-1 receptor agonist liraglutide, or with other weight-loss medications in adolescents. It was also notably larger than the placebo-adjusted 12.4 percentage point reduction achieved in adults in the STEP 1 trial.

They say the larger effect in adolescents than adults was also seen when using the trial product estimand, which accounts for factors such as medication discontinuation and consistency of medication-taking.

“The reason for this finding is currently unclear and will require further research”, the team writes in The New England Journal of Medicine.

Seventy-three percent of the adolescents given semaglutide lost at least 5% of their bodyweight, compared with 18% of the placebo group, while 62% versus 8% lost at least 10%, 53% versus 5% lost at least 15%, and 37% versus 3% lost at least 20% of their starting bodyweight.

The trial participants were aged 12 to 17 years and had a BMI in at least the 95th percentile for their age and sex or in the 85th percentile but with at least one weight-related comorbidity. Their average age was 15.4 years and their average baseline bodyweight was 107.5 kg and their BMI standard deviation score was 3.31. They were predominantly female (62%) and White (79%).

Besides their greater weight reduction, adolescents taking semaglutide had marked improvements in lipid levels, with total cholesterol falling an average of 8.3% compared with 1.3% in those taking placebo, and triglyceride levels falling an average of 28.4% versus 2.6%.

“These findings are clinically relevant, given that BMI, triglycerides, and total cholesterol levels have all been established as childhood risk factors associated with subsequent cardiovascular events in adulthood”, say the researchers.

After the 68-week treatment period, the trial participants were monitored until week 75, during which they continued to receive lifestyle counselling. At the end of this period, BMI was on average 13.2% below baseline in the semaglutide group and 1.2% above baseline in the placebo group.

Weghuber and colleagues note that “[a] longer treatment period would have provided insight into the durability of the effect of semaglutide”, observing that, in adults, weight loss was maintained for 2 years of continued treatment in the STEP 5 trial.

By contrast, adults who lost weight in the STEP 1 trial regained about two-thirds of it during the first year after stopping the medication.

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2022; doi:10.1056/NEJMoa2208601
Martin Savage
Programme Director

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medwireNews is an independent clinical news service provided by Springer Healthcare Limited. © 2023 Springer Healthcare is part of the Springer Nature Group