Cagrilintide

Overview

Cagrilintide (AM833, NN9838 or NNC0174-0833) is Novo Nordisk's investigational, long-acting amylin analogue. It has been studied as a single agent and as the amylin component of CagriSema, where it is coadministered with semaglutide.

The distinction matters: a cagrilintide monotherapy trial can support claims about cagrilintide, while a CagriSema trial supports claims about the combination. As of 20 August 2026, no cagrilintide single-agent medicine had been identified as approved in the current US or EU sources reviewed.

Verified identity and the acetate boundary

FDA GSRS records the cagrilintide active moiety as UNII AO43BIF1U8, CAS 1415456-99-3, a 37-residue peptide with sequence KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP, estimated formula C194H312N54O58S2 and calculated molecular weight 4409 Da. The record also describes an intramolecular disulfide bond, N-terminal acylation through a gamma-glutamyl/lysine linker with a C20 diacid, and a C-terminal prolinamide.

PubChem CID 164618153 is explicitly cagrilintide acetate, formula C194H312N54O59S2. The extra oxygen belongs to the acetate-form record. It must not be silently relabelled as the FDA active moiety, and a vendor's salt or formulation value must not replace the regulator's substance identity.

Mechanism and what it does not prove

In vitro and preclinical receptor pharmacology (PMID 33727283) characterises AM833 as an agonist at amylin receptors and the calcitonin receptor. These receptors are part of the calcitonin-family system involved in satiety and food intake. Albumin binding from acylation is intended to prolong exposure.

That mechanism is a biological rationale, not proof of a particular amount of weight reduction, cardiovascular benefit or long-term safety. Combination with the GLP-1 receptor agonist semaglutide is intended to engage complementary pathways, but results from that combination must stay labelled CagriSema.

Current regulatory status

Cagrilintide remains investigational as a single agent. Novo Nordisk submitted a US NDA on 18 December 2025 for CagriSema containing cagrilintide 2.4 mg and semaglutide 2.4 mg; its Q1 2026 presentation expected a US decision in Q4 2026. A filed application is not an approval and does not approve the cagrilintide component separately.

EMA decision P/0307/2023 is a product-specific paediatric waiver for cagrilintide/semaglutide, not a marketing authorisation. A case-insensitive search of the current EU Union Register dataset returned 0 matches for cagrilintide or CagriSema on the review date. These are dated, bounded checks and should be repeated after a regulator decision.

Randomised monotherapy evidence

The 26-week phase 2 trial (PMID 34798060, NCT 03856047) randomised 706 adults with overweight or obesity and without diabetes to once-weekly cagrilintide 0.3–4.5 mg, daily liraglutide 3.0 mg or placebo alongside lifestyle intervention. Under the trial-product estimand, mean weight reduction ranged from 6.0% to 10.8% across cagrilintide groups versus 3.0% with placebo.

At 4.5 mg the reported change was 10.8%, compared with 9.0% for liraglutide; the estimated difference was 1.8 percentage points (p=0.03). This was dose-finding evidence at 26 weeks, not an approved dose, not a direct comparison with current obesity medicines and not proof of durable benefit.

Early combination evidence

The phase 1b combination study (PMID 33894838, NCT 03600480) exposed 95 adults to multiple-dose cagrilintide/semaglutide regimens. Reported elimination half-lives were 159–195 hours for cagrilintide and 145–165 hours for semaglutide. These are component PK values under that protocol—not a universal half-life, approved schedule or one combined-molecule value.

The 32-week phase 2 diabetes trial (PMID 37364590, NCT 04982575) included 92 participants. Mean HbA1c change was -2.2, -1.8 and -0.9 percentage points with CagriSema, semaglutide and cagrilintide; CagriSema versus semaglutide had p=0.075. Mean weight change was -15.6%, -5.1% and -8.1%, respectively. The small trial supports further study, not an approved regimen.

CagriSema phase 3 evidence

REDEFINE 1: adults without type 2 diabetes

REDEFINE 1 (PMID 40544433, NCT 05567796) randomised 3,417 adults for 68 weeks. The treatment-policy estimand—regardless of adherence or treatment changes—reported mean weight change of -20.4% versus -3.0% with placebo. The trial-product estimand, modelling continued treatment, reported -22.7% versus -2.3%.

The estimands answer different questions and are not interchangeable. The 22.7% headline is CagriSema combination evidence, not cagrilintide-alone evidence and not a guaranteed individual result.

REDEFINE 2 and other combination populations

REDEFINE 2 (PMID 40544432, NCT 05394519) randomised 1,206 adults with type 2 diabetes. At 68 weeks, mean weight change was -13.7% versus -3.4% with placebo; gastrointestinal events occurred in 72.5% versus 34.4%. Differences in population, comparators and estimands prevent treating these figures as one expected effect for every patient.

Comparative and regional evidence

In the open-label, 84-week REDEFINE 4 comparison of CagriSema with tirzepatide 15 mg in 809 adults, Novo Nordisk reported about 23% mean weight loss with CagriSema. However, the trial failed its primary non-inferiority endpoint versus tirzepatide. This was a company-reported result at review; the large within-group change does not reverse the failed comparative endpoint.

Peer-reviewed REDEFINE 5 (PMID 42009015) studied 331 East Asian adults. Mean weight change at 68 weeks was -18.4% with CagriSema and -11.9% with semaglutide. It contributes regional combination evidence; it does not establish identical effects in all populations or cagrilintide monotherapy efficacy.

Safety and pharmacokinetic boundaries

In the cagrilintide monotherapy phase 2 trial, gastrointestinal adverse events occurred in 41–63% of cagrilintide groups versus 32% with placebo; nausea occurred in 20–47% versus 18%. Permanent discontinuation was 10% across all groups, with adverse events accounting for about 4%.

In the phase 1b combination study, 37% of 566 recorded adverse events were gastrointestinal and most events were mild or moderate. Phase 3 combination data also show frequent gastrointestinal effects. These profiles cannot prove rare-event safety, long-term outcomes or the quality of products outside trials.

Current clinical-development programme

An exact ClinicalTrials.gov intervention query for cagrilintide, checked on 20 August 2026, returned 43 records: 21 completed, 10 recruiting, 8 active, not recruiting, 2 withdrawn and 2 not yet recruiting. The query includes monotherapy and CagriSema/component-linked studies; it is not a count of positive trials.

NCT 07220642 is a phase 3 cagrilintide monotherapy study in overweight or obesity, active but not recruiting at review, with an actual start on 5 November 2025 and estimated completion on 29 June 2027. Registry status shows that a study exists; it is not an efficacy result or regulatory approval.

Russian literature and research

Two Russian-origin 2025 reviews—Berkovskaya et al. and Shestakova/Bashlykova— discuss obesity pharmacotherapy and incretin-era development. They are useful for terminology and regional scholarly context, but they are secondary sources. Naming and product-conflation errors in the Shestakova review were not used for molecular identity or regulatory claims.

A 2026 systematic review/meta-analysis (PMID 41759565) included an author affiliated with Mordovia State University, Russia. It pooled four randomised trials (n=4,419), reported high heterogeneity (I²=94.8%) and a higher gastrointestinal-event risk (RR 1.32). This is Russia-affiliated secondary synthesis, not a Russian primary trial. No Russian-origin primary human cagrilintide trial or Russian marketing authorisation was located in the accessible indexed sources reviewed.

WADA boundary and conclusion

An exact-name review of WADA's official 2026 Prohibited List resource found no named match for cagrilintide, CagriSema, GLP-1 or amylin. No S0 or other WADA class is inferred, and absence of a named match is not permission. Rules and product status can change, and athletes remain responsible for current anti-doping requirements.

Cagrilintide has meaningful human research, but it remains investigational. The most reliable reading separates active moiety from acetate, monotherapy from CagriSema, protocol PK from a regimen, and current evidence from approval.