Overview
CagriSema is the coadministration of cagrilintide, a long-acting amylin analogue, with semaglutide, a GLP-1 receptor agonist, at 2.4 mg of each once weekly. It is the one combination in this catalogue with genuine phase 3 randomised controlled trial evidence, and the numbers are worth stating exactly because they are widely misquoted.
REDEFINE 1 enrolled 3,417 adults without diabetes who had a BMI of 30 or higher, or 27 or higher with an obesity-related complication, randomised 21:3:3:7 to cagrilintide-semaglutide, semaglutide alone, cagrilintide alone, or placebo, over 68 weeks. Mean body weight change was
−20.4% with CagriSema versus −3.0% with placebo — an estimated difference of −17.3 percentage points (95% CI −18.1 to −16.6, P<0.001). Gastrointestinal adverse events affected 79.6% of the CagriSema group versus 39.9% on placebo, mainly transient and mild to moderate.
REDEFINE 2 studied 1,206 adults with type 2 diabetes and BMI 27 or higher over the same 68 weeks. Weight change was
−13.7% versus −3.4% on placebo , and 73.5% of the treatment group reached HbA1c of 6.5% or below, against 15.9% on placebo. As is typical, weight loss was smaller in the diabetes population than in the non-diabetes population.
A note on accuracy: figures around 22.7% circulate widely for CagriSema. The published NEJM phase 3 result in REDEFINE 1 is −20.4%. We cite the trial rather than the secondary sources.
Both trials were funded by Novo Nordisk (NCT05567796 and NCT05394519).
What the evidence shows
Separated by study type- HumanClinical trials and human studies
- Two phase 3a randomised, double-blind, placebo-controlled trials. REDEFINE 1 (n=3,417, without diabetes): −20.4% vs −3.0% placebo at 68 weeks. REDEFINE 2 (n=1,206, with type 2 diabetes): −13.7% vs −3.4% placebo, with 73.5% reaching HbA1c ≤6.5% versus 15.9% on placebo.
- AnimalRodent and other animal models
- Not the primary evidence base; this combination has human phase 3 data.
- In vitroCell and tissue studies
- Receptor pharmacology of both components is well characterised.
Key studies & findings
2 studies- 1
REDEFINE 1: in 3,417 adults with overweight or obesity and without diabetes, cagrilintide-semaglutide produced a mean body weight change of −20.4% versus −3.0% with placebo at 68 weeks (difference −17.3 percentage points, 95% CI −18.1 to −16.6, P<0.001). Gastrointestinal adverse events affected 79.6% versus 39.9% on placebo.
- 2
REDEFINE 2: in 1,206 adults with type 2 diabetes, body weight change was −13.7% versus −3.4% with placebo at 68 weeks, and 73.5% of the treatment group reached HbA1c ≤6.5% versus 15.9% on placebo.
Benefits & effects
3 documented−20.4% mean body weight at 68 weeks versus −3.0% placebo (REDEFINE 1)
−13.7% weight and 73.5% reaching HbA1c ≤6.5% in type 2 diabetes (REDEFINE 2)
Dual satiety pathway targeting via separate receptor systems
Side effects & safety
3 reportedSafety noteInvestigational combination not approved by any regulator. Both components are potent metabolic drugs; gastrointestinal adverse events affected roughly 80% of participants in the phase 3 obesity trial.
Gastrointestinal adverse events in 79.6% (obesity trial) and 72.5% (diabetes trial)
Nausea, vomiting, diarrhoea, constipation and abdominal pain
Not approved as a combination product by any regulator
Limitations & open questions
Not approved by any regulator as a combination product. Gastrointestinal adverse events were very common — 79.6% in the obesity trial and 72.5% in the diabetes trial — though mostly transient and mild to moderate. Both trials were funded by the manufacturer. Weight loss was substantially smaller in the type 2 diabetes population (−13.7%) than in the non-diabetes population (−20.4%), which matters for anyone generalising the headline figure. Compounded 'CagriSema' sold outside the trial setting is not the studied product: the trials used specific 2.4 mg doses of each component under supervision.
Pharmacology
A coadministered combination rather than a single chemical entity, dosed at 2.4 mg of each component once weekly in the phase 3 programme. Both components are long-acting acylated peptides engineered for weekly administration. See the individual cagrilintide and semaglutide entries for component chemistry.
Frequently asked questions
How much weight did CagriSema actually produce in trials?
−20.4% mean body weight change at 68 weeks versus −3.0% on placebo in REDEFINE 1 (adults with overweight or obesity, no diabetes), and −13.7% versus −3.4% in REDEFINE 2 (type 2 diabetes). Figures near 22.7% circulate widely but do not match the published NEJM phase 3 results.
Why combine an amylin analogue with a GLP-1 agonist?
They signal satiety through different receptor systems. Amylin is co-secreted with insulin and acts on its own pathway, while GLP-1 acts on incretin signalling, gastric emptying and central appetite pathways. Targeting both produced greater weight reduction than either alone.
How common were side effects?
Gastrointestinal adverse events — nausea, vomiting, diarrhoea, constipation, abdominal pain — affected 79.6% of the CagriSema group in REDEFINE 1 versus 39.9% on placebo. They were mainly transient and mild to moderate, but the incidence is high.
Is compounded CagriSema the same as the trial drug?
No. The trials used defined 2.4 mg doses of each component under clinical supervision, with monitoring. A compounded mixture from a research supplier is not that product and inherits none of its quality assurance.
Citations
2 sources- 1
- 2