Compound Profile
Inside CagriSema: What Cagrilintide Contributes
Published: August 25, 2026
TL;DR
Cagrilintide contributes a second receptor system to CagriSema. It is a stable, lipidated, long-acting amylin analogue with dual activity at the amylin receptor AMY1R and calcitonin receptor CTR through Gs signalling, not GLP-1 receptor agonism. In CagriSema, that amylin/calcitonin activity sits beside semaglutide's GLP-1 receptor activity.
Curo lists this material as Cagrilintide 10 mg in the research peptide catalogue. Lot documents are searchable through the COA library, and catalogue materials are supplied for research use only.
Cagrilintide supplies the amylin pathway
CagriSema is a two-part receptor pairing. Semaglutide carries the GLP-1 receptor half. Cagrilintide carries the amylin and calcitonin half. The combination is not a second incretin stacked on the first; it puts two different signalling systems into one programme, and cagrilintide is the part that makes it different from everything else in the class.
That split is also why the numbers need labels. A monotherapy arm shows what cagrilintide did on its own. A CagriSema arm measures the pair, and none of that result can be assigned to either half. Both figures are useful. They belong to different interventions, durations, comparators, and populations.
Some of the mechanism has been picked apart in animals. In rats, CagriSema produced 12 percent weight loss and a 39 percent reduction in food intake, and the authors attributed roughly a third of the weight-loss effect to preserved energy expenditure relative to pair-fed controls rather than to reduced intake alone. That is a rodent finding about the combination, not about either component by itself.
The long-acting label has human PK behind it
Long-acting is a measurement here, not a marketing word. The randomized phase 1b combination study put cagrilintide's half-life at 159 to 195 hours, with a median tmax of 24 to 72 hours and dose-proportional exposure across the 0.16 to 4.5 mg range administered. A half-life near a week is what makes once-weekly administration the design everywhere else in the programme.
The same study reported that cagrilintide did not alter semaglutide exposure or elimination, which matters for a fixed combination. That finding is specific to semaglutide under those conditions, and the wider interaction picture is still thin. Gastrointestinal disorders accounted for 207 of the 566 adverse events recorded, most of them mild to moderate.
Monotherapy established the standalone range
Before the combination reports, cagrilintide had its own dose-finding trial. The randomized phase 2 study enrolled 706 participants and administered once-weekly cagrilintide at 0.3, 0.6, 1.2, 2.4 or 4.5 mg for 26 weeks. Mean body-weight reductions ran from 6.0 to 10.8 percent across those groups against 3.0 percent with placebo. The 4.5 mg group reached 10.8 percent, against 9.0 percent for liraglutide 3.0 mg in an active comparator arm. Those amounts describe the study design and nothing else.
The tolerability figures sit right beside them. Gastrointestinal adverse events occurred in 41 to 63 percent of the cagrilintide groups against 32 percent on placebo, and nausea in 20 to 47 percent against 18 percent. Nausea, constipation, diarrhoea and administration-site reactions were the most frequent events reported.
This remains the cleanest standalone picture in the published record: 26 weeks, five dose groups, a placebo control and an active comparator.
REDEFINE measured the two-part combination
REDEFINE 1 studied CagriSema in adults with overweight or obesity and without diabetes. It randomized 3,417 participants and reported an estimated mean body-weight change at week 68 of -20.4 percent on cagrilintide 2.4 mg plus semaglutide 2.4 mg, against -3.0 percent with placebo. Gastrointestinal adverse events occurred in 79.6 percent of the combination group and 39.9 percent of the placebo group, described as mainly transient and mild to moderate.
REDEFINE 2 ran the same 2.4 mg/2.4 mg combination in adults with overweight or obesity and type 2 diabetes. It randomized 1,206 participants and reported -13.7 percent at week 68 against -3.4 percent with placebo, with gastrointestinal adverse events in 72.5 percent and 34.4 percent respectively, most of them transient and mild or moderate.
The two trials share an intervention and a 68-week endpoint and differ in population, which is most of the gap between 20.4 and 13.7 percent. Neither figure is a cagrilintide result. Both are combination results, and so are the gastrointestinal rates that come with them.
A broad programme, with an application still pending
The registered programme extends well beyond the headline trials. Across ClinicalTrials.gov searches for NNC0174-0833, cagrilintide, and CagriSema, the combined set contained 53 studies on August 25, 2026. Most completed records had no posted results. Registration shows the scale and subjects of the programme, while published outcomes remain concentrated in a smaller group of studies. A completed status alone supplies no body-weight estimate, adverse-event rate, or full account of the findings.
The regulatory position is precise. Novo Nordisk announced on December 18, 2025 that it had submitted a US new drug application for CagriSema 2.4 mg/2.4 mg, and said in the same announcement that CagriSema was not approved. No approval decision is on the record as of August 25, 2026. In Europe, cagrilintide and semaglutide appear as active substances in paediatric investigation plan EMEA-003059-PIP02-23, decision P/0307/2023 of 4 August 2023, which granted a product-specific waiver. A PIP decision is a paediatric-development matter, not a marketing authorisation.
Two adjacent FDA records get attached to cagrilintide by association, and neither one names it. The Federal Register notice for the July 2026 Pharmacy Compounding Advisory Committee meeting lists BPC-157, KPV, TB-500, MOTS-c, emideltide, Semax and Epitalon. The May 2026 notice on the section 503B bulk substances list addresses semaglutide, tirzepatide and liraglutide. Cagrilintide is in neither document.
For material identity, FDA's substance record files cagrilintide under UNII AO43BIF1U8 as a peptide amylin analogue, with a 37-residue sequence and a disulfide bridge between positions 1 and 7. PubChem carries CAS 1415456-99-3 and molecular weight around 4,409 Da. The development codes AM833 and NNC0174-0833 both appear across the registered trial records, so a search under one name alone will miss studies filed under the other.
For readers tracking how another large programme in the same therapeutic area is progressing on a different timetable, the 2026 retatrutide phase 3 programme update provides a useful parallel at a different stage.
Common questions
Is cagrilintide a GLP-1 drug?
No. It activates the amylin receptor AMY1R and the calcitonin receptor CTR, which is a separate system from the incretin receptors. How those incretin targets differ from one another is set out in the semaglutide, tirzepatide and retatrutide class comparison.
Can monotherapy and CagriSema percentages be compared as one result?
No. First identify whether the intervention was cagrilintide alone or the cagrilintide-semaglutide combination. Then compare study duration, population, comparator, and adverse-event rates before placing the percentages side by side.
Is CagriSema FDA approved?
No approval decision is on the record as of August 25, 2026. The December 2025 announcement records an NDA submission and explicitly says CagriSema was not approved.
Where does Curo explain handling and stability for research materials?
The storage and stability guide covers handling for research materials, and the guide to verifying a certificate against its lot covers the documentation check.