Why are two different weight-loss figures quoted for CagriSema?

They are different estimands. 22.7% describes participants who adhered to treatment; 20.4% describes everyone randomised regardless of adherence. Both are legitimate and they answer different questions.

Is cagrilintide a GLP-1 drug?

No. It is an amylin analogue. Amylin is a separate hormone with its own receptor and its own satiety pathway, which is why combining the two adds effect.

Is CagriSema available in the UK?

No. It is not authorised by the MHRA.

GLP-1 & Incretin Science

What Is CagriSema? Cagrilintide Plus Semaglutide

JMWritten & reviewed by Jack Muncaster · Founder, UK PeptidesLast reviewed 2026-08-232 cited sources

CagriSema is a once-weekly fixed-dose combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a GLP-1 receptor agonist, both at 2.4 mg. In the REDEFINE 1 trial it produced 22.7% mean weight reduction at 68 weeks among participants who adhered to treatment, and 20.4% across all participants regardless of adherence.

Key facts

Components: Cagrilintide 2.4 mg + semaglutide 2.4 mg
Developer: Novo Nordisk
Administration: Once weekly, subcutaneous
Trial: REDEFINE 1, 68 weeks
Efficacy estimand: 22.7% mean reduction
Treatment-policy estimand: 20.4% mean reduction
Placebo: 2.3% and 3.0% respectively

What amylin adds

Amylin is a 37-residue hormone co-secreted with insulin by pancreatic beta cells. It slows gastric emptying and signals satiety through pathways distinct from GLP-1, principally in the area postrema. Cagrilintide is a long-acting amylin analogue engineered for weekly dosing. Combining it with semaglutide targets two separate satiety mechanisms rather than pushing harder on one, which is the design rationale behind the whole amylin-combination strategy.

What REDEFINE 1 reported

REDEFINE 1 ran 68 weeks and compared CagriSema against cagrilintide alone, semaglutide alone and placebo, all once weekly. Mean weight reduction was 22.7% among participants who adhered to treatment against 2.3% on placebo, and 20.4% across all randomised participants against 3.0%. Both figures are correct; they answer different questions, and which one gets quoted changes the apparent result by more than two percentage points.

The threshold results

Proportions reaching each level of reduction at 68 weeks were reported as follows. A supportive analysis also found that 50.7% of participants with obesity reached a BMI below 30 by end of treatment, from a mean baseline BMI of 38, against 10.2% on placebo.

≥5% reduction — 97.6% of participants
≥20% reduction — 60.2%
≥25% reduction — 40.4%
≥30% reduction — 23.1%
Reached BMI below 30 — 50.7% (vs 10.2% placebo)

How it compares with retatrutide

Retatrutide's TRIUMPH-1 reported 28.3% at 80 weeks against CagriSema's 22.7% at 68 weeks. The comparison is indirect and the durations differ, so the gap should not be read as precise. What is clear is that both approaches — adding amylin, and adding GIP plus glucagon — produce substantially more reduction than GLP-1 alone.

Status

CagriSema results were presented at the American Diabetes Association's 85th Scientific Sessions and published simultaneously in the New England Journal of Medicine. It is under regulatory review rather than authorised, and is not available in the UK.

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 are two different weight-loss figures quoted for CagriSema?: They are different estimands. 22.7% describes participants who adhered to treatment; 20.4% describes everyone randomised regardless of adherence. Both are legitimate and they answer different questions.
Is cagrilintide a GLP-1 drug?: No. It is an amylin analogue. Amylin is a separate hormone with its own receptor and its own satiety pathway, which is why combining the two adds effect.
Is CagriSema available in the UK?: No. It is not authorised by the MHRA.

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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