Cagrilintide

Cagrilintide (Novo Nordisk code NNC0174-0833) is a synthetic, long-acting analogue of human amylin, the 37-residue peptide co-secreted with insulin by pancreatic beta cells. Native amylin has a half-life of minutes and a strong tendency to aggregate into amyloid fibrils. Cagrilintide retains the amylin backbone with several substitutions that suppress fibrillation, and adds a C20 fatty-diacid side chain that binds albumin, extending exposure to the once-weekly range [4]. It is a dual amylin and calcitonin receptor agonist (a DACRA): it activates the calcitonin receptor and the amylin receptors formed when the calcitonin receptor partners with receptor activity-modifying proteins (RAMPs) [4][7]. It is supplied here as a lyophilised research peptide for in-vitro study of amylin-receptor pharmacology.

Mechanism

Amylin signals largely through the area postrema and nucleus of the solitary tract in the hindbrain, regions with a permeable blood–brain barrier, and its physiological actions in published work include slowing of gastric emptying, suppression of post-prandial glucagon and reduction of meal size [7]. Because these effects are mechanistically distinct from GLP-1 receptor signalling, amylin analogues have been examined as partners for GLP-1 agonists in the hope of additive effects on intake without overlapping receptor desensitisation [2].

The receptor biology is unusual. Amylin has no receptor of its own: the calcitonin receptor (CTR) becomes an amylin receptor (AMY1, AMY2 or AMY3) when it heterodimerises with RAMP1, RAMP2 or RAMP3, and the RAMP partner changes ligand selectivity and trafficking [7]. Cagrilintide was developed by lipidating a fibrillation-resistant amylin backbone and screening analogues for balanced CTR and AMY-receptor potency together with low aggregation propensity and slow albumin off-rate; the medicinal-chemistry paper reports the resulting once-weekly pharmacokinetic profile in rats, dogs and humans [4].

What the published trials report

• Phase 2 monotherapy (n = 706; 26 weeks): once-weekly cagrilintide 4.5 mg produced a mean body-weight change of −10.8% versus −3.0% with placebo and −9.0% with once-daily liraglutide 3.0 mg; gastrointestinal events were most common [1].
• Phase 1b with semaglutide (n = 95; 20 weeks): cagrilintide 2.4 mg co-administered with semaglutide 2.4 mg produced a mean change of −17.1% versus −9.8% with semaglutide plus placebo, with acceptable tolerability in this small sample [2].
• Phase 2 in type 2 diabetes (n = 92; 32 weeks): the combination (branded CagriSema in the trial literature) reported −15.6% body weight versus −5.1% with semaglutide alone and −8.1% with cagrilintide alone, with HbA1c reductions of 2.2 percentage points [3].
• REDEFINE 1 (n = 3,417; 68 weeks, phase 3): coadministered cagrilintide–semaglutide 2.4 mg/2.4 mg produced a mean change of −20.4% versus −3.0% with placebo under the treatment-policy estimand, with −22.7% on the trial-product estimand. Adverse events were predominantly gastrointestinal and led to discontinuation in 6.0% of the combination group [5].
• REDEFINE 2 (n = 1,206 with type 2 diabetes; 68 weeks): −13.7% versus −3.4% with placebo [6].

Why it is used as a research tool

Cagrilintide is a reference compound for experiments distinguishing amylin-receptor from calcitonin-receptor signalling, for RAMP-dependence assays in cells co-expressing CTR with RAMP1–3, for fibrillation and thioflavin-T studies where a non-aggregating amylin analogue is needed as a control, and for rodent work on hindbrain satiety circuits [4][7]. Its long albumin-mediated half-life makes it a useful comparator in protein-binding and formulation studies.

What the research does not establish

All clinical outcomes above were produced with GMP-manufactured drug under medical supervision in structured trials, and cagrilintide itself remains an investigational compound not approved as a stand-alone medicine anywhere at the time of writing. The trials were of fixed duration and do not describe what happens after treatment stops, nor outcomes in populations they excluded. The research-grade peptide sold here has not been evaluated by the FDA, is not manufactured for administration to people or animals, and nothing on this page describes a benefit in a person.

Format. Lyophilised white powder in a sealed glass vial. Net peptide content is stated on the certificate of analysis.

Reconstitution. Add bacteriostatic water or sterile water for injection-grade solvent slowly against the vial wall and swirl gently; amylin analogues are sensitive to shear and should never be shaken or vortexed. Use the reconstitution calculator to derive concentration from vial mass and diluent volume.

Storage. Lyophilised: −20°C long-term, protected from light and moisture. Reconstituted: 2–8°C, do not freeze, use within the laboratory’s validated period.

Handling. Gloves and eye protection; treat as a bioactive peptide. Minimise headspace and avoid repeated freeze–thaw. For in-vitro laboratory research only — not for human or veterinary use.