Why don't paediatric trials report weight loss?

Because participants are still growing. Measuring weight reduction would penalise normal growth and reward its absence.

What is z-score compression?

The BMI distribution is highly skewed at the top, so above the 95th percentile a large change in real BMI produces only a small change in z-score.

Can I compare a paediatric figure with an adult one?

No. One is percent change in BMI, the other percent change in body weight. They are different measurements.

GLP-1 & Incretin Science

The Endpoint Changes When the Patient Is Still Growing

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

Adult obesity trials report percentage change in body weight. Trials in children and adolescents report percent change in body mass index instead, because a growing participant can gain height and weight simultaneously while their adiposity falls.

Key facts

Adult endpoint: Percent change in body weight
Paediatric endpoint: Percent change in BMI
Reason: Height is still increasing
Registry example: NCT06075667 primary outcome is BMI
Assessment standard: Growth reference percentiles
Known measurement problem: z-scores compress above the 95th percentile

Why body weight is the wrong endpoint in a growing person

An adolescent who grows several centimetres over a 68-week trial should gain some weight. Measuring success as weight reduction would penalise normal growth and reward its absence, which is precisely the wrong incentive. BMI accounts for height, so it can fall while absolute weight holds steady or rises.

How obesity is defined differently in children

Adults are assessed against fixed BMI thresholds. Children are assessed against growth reference charts, because normal BMI varies substantially with age and sex through childhood. A child is classified by where they sit relative to a reference population of the same age and sex — commonly at or above the 95th percentile.

Research material referenced

Retatrutide 10mg — third-party HPLC tested

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The measurement problem that follows

The natural way to express position on a growth chart is a z-score, the number of standard deviations from the reference mean. But the distribution is highly skewed at the upper end, so z-scores compress severely above the 95th percentile — a large change in actual BMI produces a small change in z-score. Wei and colleagues addressed exactly this in the Annals of Human Biology in 2020, publishing a method for calculating z-scores and percentiles above the 95th percentile.

Why that matters for trials specifically

Severe paediatric obesity sits precisely in the compressed region. A trial reporting change in z-score would understate a real effect, and two trials using different handling of the upper tail would not be comparable. Reporting percent change in BMI avoids the compression entirely, which is why registered trials use it — NCT06075667 lists its primary outcome as percent change from baseline in body mass index.

What this means for reading a headline

A paediatric figure and an adult figure are not the same measurement. STEP TEENS reported a 16.1% mean change in BMI; adult semaglutide trials report percentage weight loss. Setting those numbers beside each other as though they described the same thing is a category error, and it happens routinely.

What this site is and is not describing

Registered clinical trials in defined paediatric populations, conducted under clinical supervision with ethics approval and specialist oversight. Nothing supplied here is a licensed medicine, is related to any of these compounds, or has any place in the care of a child.

Quick reference

	Adult trials	Paediatric trials
Primary endpoint	% change in body weight	% change in BMI
Obesity defined by	Fixed BMI thresholds	Growth reference percentile
Complication	—	z-score compression above 95th centile

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

Why don't paediatric trials report weight loss?: Because participants are still growing. Measuring weight reduction would penalise normal growth and reward its absence.
What is z-score compression?: The BMI distribution is highly skewed at the top, so above the 95th percentile a large change in real BMI produces only a small change in z-score.
Can I compare a paediatric figure with an adult one?: No. One is percent change in BMI, the other percent change in body weight. They are different measurements.

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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