How is an umbrella study different from a platform trial?

The terms overlap and are used loosely. An umbrella study typically evaluates several interventions within one disease under a shared protocol. A platform trial adds the ability to enter and drop arms over time against a shared, often adaptive, control. A basket trial does the opposite of both: one intervention across several diseases. SOLIS-1 is registered as an umbrella study with three fixed cohorts.

Does combining amylin with GLP-1 work?

There is Phase 3 evidence for one such combination - cagrilintide with semaglutide - and Phase 1 and 2 evidence for others. Whether it works for this particular pair is what SOLIS-1 exists to find out. The general principle being established for one pair does not transfer to another pair, because the answer depends on the specific molecules, their exposure profiles and their dose ratios.

What does 872 participants buy in Phase 2b?

Enough to compare several dose levels against placebo with reasonable precision, and to see common adverse events. It is not enough to characterise uncommon safety signals, which is why Phase 3 obesity programmes run into the thousands.

Research & Regulatory News

SOLIS-1: Testing Two Compounds and Their Combination at Once

JMWritten & reviewed by Jack Muncaster · Founder, UK PeptidesLast reviewed 2026-08-234 cited sources

SOLIS-1 (NCT07575932) is a Phase 2b umbrella study enrolling an estimated 872 adults with overweight or obesity. It tests PF-08653945, an amylin analogue, and PF-08653944 (berobenatide), alone or in combination, across three separate cohorts, with a primary completion date of 4 August 2027.

Key facts

Registration: NCT07575932
Registered acronym: SOLIS-1
Design: Phase 2b, randomised, double-blind, placebo-controlled, dose-ranging umbrella study
Enrolment: 872 (estimated)
Compounds: PF-08653945 (amylin analogue) and PF-08653944 (berobenatide)
Cohorts: 3
Status: Recruiting
Primary completion: 4 August 2027
Sponsor: Pfizer

What an umbrella study is, and why this one is

The registered title calls SOLIS-1 an umbrella study, which has a specific meaning. A conventional trial answers one question about one intervention. An umbrella study runs several sub-studies under a shared protocol, infrastructure and often a shared control group, so that multiple interventions are evaluated in one operational machine. The savings are real: one set of sites, one data-monitoring committee, one set of eligibility criteria, and - crucially - participants recruited into a common pool rather than competing trials. The cost is complexity, and the risk is that a shared control group creates comparisons the design was never powered to support.

The three cohorts

Cohort 1 gives PF-08653945 or placebo. Cohort 2 gives PF-08653945 plus PF-08653944, or placebo. Cohort 3 gives PF-08653945 plus PF-08653944, or PF-08653944 alone, or placebo. Read together, that structure lets the sponsor characterise the amylin analogue on its own, the combination, and - in cohort 3 only - the combination against its own GLP-1 component within a randomised comparison. That last point is the one that matters scientifically. A combination that beats placebo tells you very little; a combination that beats its own more established component is the only evidence that adding the second agent did anything.

What PF-08653945 is

PF-08653945, also written PF'3945 and previously MET-233i, is an amylin analogue engineered for monthly dosing. Its Phase 1 data, reported by Metsera in June 2025, came from a randomised, placebo-controlled, double-blind trial in 80 people with overweight or obesity and without type 2 diabetes, using single doses from 0.15 mg to 2.4 mg and multiple doses from 0.15 mg to 1.2 mg given weekly over five weeks. The reported observed half-life was 19 days and mean placebo-subtracted weight loss reached 8.4% at day 36 after five weekly 1.2 mg doses. Gastrointestinal adverse events were described as mild, dose-dependent and mostly confined to the first week.

Why the pharmacokinetics are the point

The stated rationale for combining these two specific molecules is not that amylin and GLP-1 agonism are complementary - that argument applies to cagrilintide with semaglutide and to petrelintide programmes too. It is that the amylin analogue's exposure profile after multiple doses matched that of the GLP-1 agonist. Two drugs can only share a fixed-dose monthly injection if their concentration-time curves are compatible; otherwise one is at trough while the other is at peak, and the ratio the trial tested is not the ratio the patient receives. Combinability here is a pharmacokinetic achievement before it is a pharmacological one, and that is the part most coverage skips.

What SOLIS-1 will and will not settle

It is a dose-ranging Phase 2b study. Its job is to select doses and characterise tolerability well enough to design Phase 3, not to establish efficacy for registration. Primary completion is August 2027. Nothing in it will be pivotal evidence, and neither compound is licensed anywhere. Neither is supplied on this site.

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

How is an umbrella study different from a platform trial?: The terms overlap and are used loosely. An umbrella study typically evaluates several interventions within one disease under a shared protocol. A platform trial adds the ability to enter and drop arms over time against a shared, often adaptive, control. A basket trial does the opposite of both: one intervention across several diseases. SOLIS-1 is registered as an umbrella study with three fixed cohorts.
Does combining amylin with GLP-1 work?: There is Phase 3 evidence for one such combination - cagrilintide with semaglutide - and Phase 1 and 2 evidence for others. Whether it works for this particular pair is what SOLIS-1 exists to find out. The general principle being established for one pair does not transfer to another pair, because the answer depends on the specific molecules, their exposure profiles and their dose ratios.
What does 872 participants buy in Phase 2b?: Enough to compare several dose levels against placebo with reasonable precision, and to see common adverse events. It is not enough to characterise uncommon safety signals, which is why Phase 3 obesity programmes run into the thousands.

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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