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STEP TEENS: what the adolescent trial actually measured

A 16.1 per cent BMI reduction over 68 weeks, and 73 per cent reaching five per cent weight loss. The endpoint is BMI, not weight, and five participants developed gallstones.

Ruth Alvarez5 min read
Mean BMI change at 68 weeksSemaglutide 2.4 mg−16.1%Placebo+0.6%Reaching 5% weight loss:73% on drug · 18% on placebo

Adolescent prescribing is where this drug class gets least comfortable and least studied, and STEP TEENS is the trial people are arguing about. It randomized 201 participants aged 12 to under 18 with obesity, two to one, to semaglutide 2.4 mg or placebo for 68 weeks, both arms receiving lifestyle intervention [1]. Ninety per cent completed treatment. The effect is the largest in the literature for this age group, and the way it is measured is worth reading closely before it reaches a purchasing decision.

What the trial measured

The primary endpoint was the percentage change in BMI, not in body weight. Mean BMI fell 16.1 per cent on semaglutide and rose 0.6 per cent on placebo, an estimated difference of 16.7 percentage points (95% CI −20.3 to −13.2, P < 0.001). In a population still growing in height, BMI change and weight change are different quantities, and the trial chose the one that accounts for growth.

The confirmatory secondary endpoint was weight loss of at least 5 per cent: 95 of 131 participants on semaglutide reached it, against 11 of 62 on placebo — 73 per cent against 18 per cent, an odds ratio of 14.0 (95% CI 6.3 to 31.0). Waist circumference, glycated hemoglobin, lipids other than HDL, and alanine aminotransferase all improved more on the drug.

What it cost

Gastrointestinal adverse events occurred in 62 per cent on semaglutide against 42 per cent on placebo. Serious adverse events were reported in 15 of 133 on the drug and 6 of 67 on placebo, 11 per cent against 9. Five participants on semaglutide developed gallstones and none on placebo did.

Five of 133 is a small number and it points the same way as the much larger gallbladder meta-analysis, whose weight-loss subgroup carried nearly double the pooled risk. In adolescents that finding has a longer horizon attached to it than it does in adults.

What this does not settle

Sixty-eight weeks is not adolescence. The trial says nothing about what happens over the years a 14-year-old has ahead of them, nothing about stopping, and nothing about bone accrual during growth — a question the post-surgical body-composition data raises in adults with far less at stake.

One practical note for anyone reading this as a parent. Adolescent prescribing is a specialist decision, and almost none of the telehealth sellers tracked here publish anything about age criteria, pediatric oversight or who reviews a case — the gap counted in the disclosure census. That absence is the relevant fact here, more than any figure in the trial.

Frequently asked

How much weight did adolescents lose?
The primary endpoint was BMI, which fell 16.1 per cent against a 0.6 per cent rise on placebo. On the weight endpoint, 73 per cent reached at least 5 per cent loss against 18 per cent on placebo.
Why measure BMI rather than weight?
Because adolescents are still growing in height, so BMI change accounts for growth in a way weight change does not. The two are different quantities in this population.
What were the harms?
Gastrointestinal events in 62 per cent against 42 on placebo, serious adverse events in 11 per cent against 9, and gallstones in five of 133 participants on the drug against none on placebo.

Sources

  1. [1] Weghuber D, et al. (2022). Once-Weekly Semaglutide in Adolescents with Obesity New England Journal of Medicine. PMID 36322838

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