What did STEP TEENS find?

Mean BMI change at 68 weeks of −16.1% with semaglutide against +0.6% with placebo among 201 randomised adolescents.

Were there safety findings?

Gastrointestinal adverse events in 62% versus 42%, and cholelithiasis in 5 participants (4%) on semaglutide with none on placebo.

Is there long-term data?

No. The trial ran 68 weeks, and long-term adolescent data does not exist for any compound in this class.

GLP-1 & Incretin Science

STEP TEENS and What It Reported

JMWritten & reviewed by Jack Muncaster · Founder, UK PeptidesLast reviewed 2026-08-233 cited sources

Weghuber and colleagues published STEP TEENS in the New England Journal of Medicine in December 2022. Among 201 randomised adolescents, mean BMI change at week 68 was −16.1% with semaglutide against +0.6% with placebo — an estimated difference of −16.7 percentage points.

Key facts

Published: NEJM, 15 December 2022 (PMID 36322838)
Randomised: 201
Completed treatment: 180 (90%)
Duration: 68 weeks
Mean BMI change: −16.1% vs +0.6% placebo
Estimated difference: −16.7 points (95% CI −20.3 to −13.2)
≥5% weight loss: 73% vs 18% (OR 14.0)
GI adverse events: 62% vs 42%

What the trial established

That a GLP-1 receptor agonist produces substantial BMI reduction in adolescents with obesity over 68 weeks. The primary result — −16.1% against +0.6% — is a large separation, and the confidence interval on the difference runs from −20.3 to −13.2 percentage points, which is a precise as well as a large effect.

The completion rate is part of the result

180 of 201 participants, 90%, completed treatment. That is high for a 68-week trial in any population and unusually so in adolescents, who are generally harder to retain. A high completion rate narrows the gap between what the efficacy and treatment-policy estimands would show, which makes the headline figure more robust than it would otherwise be.

Research material referenced

Retatrutide 10mg — third-party HPLC tested

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The secondary endpoint that gets quoted most

73% of participants on semaglutide, 95 of 131, achieved weight loss of 5% or more, against 18% on placebo — 11 of 62. The odds ratio is 14.0 with a confidence interval from 6.3 to 31.0. That is the figure most often repeated, and it is a secondary endpoint measured in weight rather than the BMI primary.

The safety finding that rarely gets repeated

Cholelithiasis — gallstones — occurred in 5 participants, 4%, in the semaglutide group and in none on placebo. Rapid weight reduction is an established risk factor for gallstone formation, so this is mechanistically expected rather than surprising, and it belongs beside the efficacy numbers rather than in a footnote.

The rest of the safety picture

Gastrointestinal adverse events occurred in 62% on semaglutide against 42% on placebo — a substantial excess, and consistent with the drug class throughout. Serious adverse events were reported in 11% of the semaglutide group and 9% of placebo, which is a much smaller difference than the gastrointestinal figures suggest.

What the trial does not settle

What happens after 68 weeks, in a population who may be treated for decades. Long-term data in adolescents does not exist for any compound in this class, and the questions about growth, puberty and duration of exposure are open because the trials that would answer them have not been run.

The necessary boundary

Semaglutide is a licensed medicine, and STEP TEENS was a registered trial conducted under clinical supervision with ethics approval and specialist paediatric oversight. Nothing supplied on this site is semaglutide, is related to it, or is appropriate for any person, least of all a child.

Extended research context

The GLP-1 & Incretin Science deep dive

Deep dive: the two routes to a bigger effect

Every compound trying to beat GLP-1 alone has taken one of two routes. The first adds more receptors from the same hormone family — GIP in tirzepatide, GIP and glucagon in retatrutide. The second adds a non-incretin satiety hormone, which in practice means amylin: CagriSema combines cagrilintide with semaglutide, and amycretin engages both receptors from one molecule. Both routes work, because they recruit signalling pathways that do not fully overlap. Neither has escaped the constraint that binds all of them, which is that gastrointestinal tolerability worsens as effect size grows.

Deep dive: why a percentage is not a result

The most-quoted numbers in this field are the least comparable. REDEFINE 1 reported 22.7% and 20.4% for the same compound in the same trial — the first among participants who adhered to treatment, the second across everyone randomised. TRIUMPH-1 reported 28.3% in an uncomplicated obesity population while TRIUMPH-3 reported up to 22.6% in adults with established cardiovascular disease, using the same compound. Before any two figures can be compared they have to match on estimand, population, duration, comparator and whether the number is placebo-adjusted. Most published comparisons match on none of them.

Deep dive: what happens after the trial stops

Every headline figure describes weight while treatment continues. The STEP-1 extension found that a year after semaglutide was stopped, participants had given back roughly two-thirds of what they lost, moving from 17.3% mean reduction to a net 5.6% — though average weight remained below baseline and nearly half stayed at least 5% down. Meta-analysis puts regain at around 0.8 kg per month. This is why maintenance studies such as TRIUMPH-6 matter more to the field's future than another two points of peak reduction.

Research applications

▸Comparing incretin and amylin compounds on a like-for-like basis
▸Interpreting estimands, thresholds and placebo-adjusted figures in trial reports
▸Tracking the obesity pipeline across sponsors and jurisdictions
▸Understanding receptor pharmacology behind GLP-1, GIP, glucagon and amylin
▸Distinguishing licensed medicines from investigational compounds

Handling checklist

✓Identify which estimand a quoted percentage comes from before citing it
✓Check the trial population and baseline BMI against the comparison you are making
✓Confirm the duration and whether the reduction curve had plateaued
✓Read discontinuation rates alongside efficacy figures
✓Verify every NCT identifier against ClinicalTrials.gov rather than secondary reporting

Common research-handling mistakes

Learnt from thousands of researcher orders across our UK labs.

✗ Comparing headline percentages across different trials

Fix: Population, duration, estimand and comparator all differ; the numbers are not interchangeable.

✗ Quoting the larger of two figures from the same trial

Fix: Name the estimand. Efficacy and treatment-policy answer different questions.

✗ Treating peak reduction as a durable outcome

Fix: Substantial regain follows cessation across the class; peak figures describe a maintained state.

✗ Assuming an oral route means a weaker mechanism

Fix: Route and receptor count are independent. Orforglipron is weaker because it hits one receptor, not because it is a tablet.

✗ Reading investigational compounds as available treatments

Fix: Most of this pipeline holds no authorisation anywhere; mazdutide is approved only in China.

Continue researching

Peer-reviewed guides, comparators and matched reference materials.

Frequently asked questions

What did STEP TEENS find?: Mean BMI change at 68 weeks of −16.1% with semaglutide against +0.6% with placebo among 201 randomised adolescents.
Were there safety findings?: Gastrointestinal adverse events in 62% versus 42%, and cholelithiasis in 5 participants (4%) on semaglutide with none on placebo.
Is there long-term data?: No. The trial ran 68 weeks, and long-term adolescent data does not exist for any compound in this class.

Primary sources & clinical trials

Peer-reviewed research and registered trials from PubMed, ClinicalTrials.gov, PubChem, FDA and NIH. All links open in a new tab and point to the primary source, so every claim can be verified at origin.

Written and reviewed by

Jack Muncaster · Founder, UK Peptides

Jack founded UK Peptides in Manchester after repeatedly receiving research compounds with missing or recycled paperwork. He is responsible for supplier selection, batch release decisions and the content published in this research library. Every article here is sourced to primary literature and every product page to a signed third-party certificate.

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