What were the trial's primary endpoints?

Two — percentage change in body weight and change in WOMAC pain score. Moving both is a harder test than either alone.

A patient-reported instrument covering pain, stiffness and physical function in osteoarthritis. It measures symptoms rather than joint structure.

Does it show the joint disease was slowed?

No. Symptomatic improvement is not structural evidence, which would require imaging endpoints and much longer follow-up.

Research & Regulatory News

A Trial That Had to Move Two Things at Once

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

Bliddal and colleagues published once-weekly semaglutide in persons with obesity and knee osteoarthritis in the New England Journal of Medicine in October 2024. The trial, NCT05064735, enrolled 407 participants with co-primary endpoints of percentage change in body weight and change in WOMAC pain score.

Key facts

Registration: NCT05064735
Registered acronym: None
Phase: 3
Enrolment: 407
Status: Completed
Primary completion: 24 July 2023
Co-primary 1: Percentage change in body weight
Co-primary 2: Change in WOMAC pain score
Published: NEJM, 31 October 2024 (PMID 39476339)

Why two co-primary endpoints is the notable design choice

The registry lists both percentage change in body weight and change in WOMAC pain score as primary outcomes. Requiring a trial to move two endpoints is a harder test than either alone, and it reflects the specific claim being made — not that the drug reduces weight, which was established, but that doing so changes what the joint disease does to people.

What WOMAC measures

The Western Ontario and McMaster Universities Osteoarthritis Index is a patient-reported instrument covering pain, stiffness and physical function. It asks people what they experience rather than measuring cartilage on a scan, which makes it a symptomatic endpoint — and symptoms are what bring people with osteoarthritis to clinicians.

Research material referenced

Retatrutide 10mg — third-party HPLC tested

View — £59.99

Why the mechanical argument is strong here

The knee bears load, and the force it experiences during walking is several times body weight because muscle contraction across the joint adds to gravitational load. Reducing body mass therefore reduces joint force by a multiple of the mass lost. Unlike most indications for this class, the primary mechanism requires nothing beyond the weight change itself.

What it does not establish

Structural change. A symptomatic improvement is not evidence that cartilage was preserved or that disease progression slowed. Those are separate endpoints requiring imaging and much longer follow-up, and osteoarthritis has a long history of symptomatic effects that did not translate into structural ones.

The naming point, for the third time

NCT05064735 carries no registered acronym. This site has now found three widely discussed trials in the same position — the CagriSema head-to-head and the tirzepatide adolescent Phase 3 being the others. Searching a programme name on ClinicalTrials.gov can return nothing while the trial exists under its number.

How this fits the indication pattern

Cardiovascular events, kidney events, liver histology, heart failure, walking capacity in peripheral artery disease and now joint symptoms. The pattern is a metabolic agent being assessed organ system by organ system, with osteoarthritis unusual in that the proposed mechanism is mechanical rather than metabolic.

The boundary

Semaglutide is a licensed medicine and this was a registered trial conducted under clinical supervision. Nothing supplied on this site is semaglutide, is related to it, or is an alternative to any treatment for osteoarthritis.

Extended research context

The Research & Regulatory News deep dive

Deep dive: why 2026 was the year the incretin field split in two

For a decade every meaningful GLP-1 medicine was a peptide, and every one of them was injected. 2026 broke that pattern in both directions at once. In August the MHRA authorised orforglipron, a small molecule with no peptide bonds that works as an ordinary daily tablet. Three months earlier, retatrutide's TRIUMPH-1 reported a 28.3% mean weight reduction — the largest figure yet from a single molecule, and achievable only with a peptide capable of engaging three receptors at once. The field is not converging on one answer; it is separating into a convenience track and a magnitude track, and those tracks have different chemistry.

Deep dive: what a marketing authorisation actually means

An authorisation is granted to a specific product, in a specific formulation, for a specific indication, by a specific regulator. It is not a statement about a compound class and it does not transfer. Orforglipron being licensed in the UK tells you nothing about the legal or regulatory status of any other incretin, and nothing at all about compounds that remain investigational. Authorisation is also separate from funding: a licensed medicine is not automatically available on the NHS, which requires a further NICE appraisal.

Deep dive: reading trial results without being misled

Headline percentages are the least transferable part of a trial. A figure is only meaningful alongside its population, its duration, its comparator and its dropout rate. TRIUMPH-1's 28.3% came from an 80-week study in a relatively uncomplicated obesity population; TRIUMPH-3's 22.6% came from adults with severe obesity and established cardiovascular disease, and the gap between those two numbers is mostly population, not potency. Discontinuation rates deserve the same attention as efficacy: 11.3% of the TRIUMPH-1 12 mg arm stopped due to adverse events against 4.9% on placebo, and that figure is routinely dropped from summaries.

Research applications

▸Tracking regulatory status of investigational incretin compounds
▸Understanding the difference between authorisation, NICE appraisal and NHS availability
▸Comparing peptide and non-peptide receptor agonist pharmacology
▸Interpreting Phase 3 topline releases before peer-reviewed publication
▸Verifying trial identity against ClinicalTrials.gov registrations

Handling checklist

✓Check the compound named in a trial registration matches the compound being discussed
✓Confirm the NCT identifier resolves to the acronym being cited
✓Read topline press releases as preliminary until peer-reviewed publication
✓Separate the trial population from the headline percentage before comparing studies
✓Treat authorisation in one jurisdiction as saying nothing about status in another

Common research-handling mistakes

Learnt from thousands of researcher orders across our UK labs.

✗ Treating a positive Phase 3 as approval

Fix: Filing begins a review that commonly takes a year or more and can end in a request for more data.

✗ Comparing weight-reduction percentages across different trials

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

✗ Assuming one incretin's approval legitimises another compound

Fix: Authorisations are product-specific and do not transfer between compounds.

✗ Citing a TRIUMPH number without checking the NCT identifier

Fix: Verify against ClinicalTrials.gov — the numbering has been widely misreported.

✗ Reading research material as an alternative to a licensed medicine

Fix: Research material is supplied for laboratory use only and is not a substitute for anything prescribed.

Continue researching

Peer-reviewed guides, comparators and matched reference materials.

Frequently asked questions

What were the trial's primary endpoints?: Two — percentage change in body weight and change in WOMAC pain score. Moving both is a harder test than either alone.
What is WOMAC?: A patient-reported instrument covering pain, stiffness and physical function in osteoarthritis. It measures symptoms rather than joint structure.
Does it show the joint disease was slowed?: No. Symptomatic improvement is not structural evidence, which would require imaging endpoints and much longer follow-up.

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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