Cagrilintide is a long-acting amylin analog (~7-day half-life) developed for once-weekly combination dosing with semaglutide — the most clinically advanced amylin compound, with Phase 3 REDEFINE data published.
Product definition
What is Cagrilintide?
Cagrilintide is a long-acting amylin analog (~7-day half-life) developed for once-weekly combination dosing with semaglutide — the most clinically advanced amylin compound, with Phase 3 REDEFINE data published.
Cagrilintide is a synthetic amylin analog developed by Novo Nordisk. Amylin (islet amyloid polypeptide, IAPP) is a 37-amino-acid peptide co-secreted with insulin from pancreatic beta cells, acting on calcitonin receptor/RAMP1, RAMP2, and RAMP3 complexes to modulate satiety, glucagon secretion, and gastric emptying. Cagrilintide's modifications from native amylin include structural stabilizations to prevent the aggregation propensity of native IAPP and a C18 fatty acid conjugate for albumin binding, achieving a ~7-day half-life versus native amylin's minutes-long clearance.
The investigational CagriSema program combines cagrilintide with semaglutide in a fixed-ratio subcutaneous formulation. The REDEFINE Phase 3 program (REDEFINE-1, -2, -3) is the most comprehensive prospective evaluation of an amylin + GLP-1RA combination in the obesity research literature, producing the highest-powered Phase 3 dataset for amylin pharmacology published to date.
Research context
How is Cagrilintide described in the research literature?
Cagrilintide activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and nucleus tractus solitarius, producing satiety signals, glucagon suppression, and gastric motility effects distinct from GLP-1R pathways. C18 fatty acid modification enables ~7-day half-life for weekly dosing. REDEFINE-1 Phase 3 showed 22.7% body weight reduction in combination with semaglutide 2.4 mg.
Compound profile
Key facts about Cagrilintide
- Class
- Long-acting amylin analog
- Target
- Calcitonin receptor + RAMP1/2/3 complexes (amylin receptors)
- Molecular weight
- ~4,030 Da
- Half-life
- ~7 days (albumin-bound in vivo)
- Developer
- Novo Nordisk
- Phase 3 result
- 22.7% body weight reduction in combination with semaglutide (REDEFINE-1)
- Research category
- Amylin pharmacology, satiety neuroscience, combination obesity research
- Storage
- Lyophilized: −20°C. Reconstituted: 2–8°C, use within 30 days
Research areas
What research areas is Cagrilintide associated with?
- ~7-day half-life via C18 fatty acid modification — once-weekly dosing in the REDEFINE clinical program
- Amylin receptor mechanism pharmacologically distinct from GLP-1R — separate receptor system, complementary satiety
- REDEFINE-1 Phase 3: 22.7% mean body weight reduction in combination with semaglutide 2.4 mg at 68 weeks
- Most clinically advanced amylin analog — Phase 3 data distinguishes it from preclinical-only amylin compounds
- Glucagon suppression via amylin receptor adds metabolic benefit beyond GLP-1R activation alone
- Reference compound for amylin receptor pharmacology, neuroendocrine satiety research
Research audience
Who researches Cagrilintide?
Cagrilintide is used by researchers studying amylin receptor pharmacology, neuroendocrine satiety signaling, combination incretin strategies, obesity mechanisms, and beta cell co-secretion biology. It is the reference long-acting amylin compound for investigators requiring Phase 3-validated amylin pharmacology data.
Preclinical research overview
What does the preclinical literature say about Cagrilintide?
The amylin receptor system has been under investigation since the original characterization of IAPP in the 1980s. Pramlintide (Symlin) — a short-acting amylin analog — achieved FDA approval in 2005 for adjunct therapy in T1D and T2D, establishing amylin receptor agonism as a clinically valid pharmacological approach. However, pramlintide's multiple-daily-injection requirement limited its utility.
Cagrilintide represents the technical advance of applying long-acting fatty acid modification technology (previously used in semaglutide and insulin degludec) to the amylin class, enabling weekly dosing and combination with semaglutide in a single injection.
The REDEFINE program was designed with the explicit hypothesis that combining two mechanistically distinct receptor systems (amylin + GLP-1R) would produce additive weight reduction beyond either alone. REDEFINE-1 results confirmed this hypothesis: 22.7% vs semaglutide alone (approx. 15%) in comparable populations, suggesting approximately 7-8 additional percentage points of weight reduction attributable to the amylin receptor component.
Common questions
Frequently asked about Cagrilintide
How is cagrilintide pharmacologically different from GLP-1 agonists like semaglutide?
Cagrilintide and semaglutide engage completely different receptor systems. Semaglutide acts on GLP-1 receptors in pancreatic beta cells, hypothalamic satiety circuits, and the GI tract. Cagrilintide acts on amylin receptors (calcitonin receptor + RAMP complexes) predominantly in brainstem structures (area postrema, NTS) and hypothalamic regions with different anatomical distribution from GLP-1R. The pharmacological independence of the two receptor systems is the basis for the additive weight reduction observed in the REDEFINE program.
What has cagrilintide shown in standalone (monotherapy) research?
Cagrilintide monotherapy has been studied in Phase 2 research, producing approximately 10.8% body weight reduction at 26 weeks (4.5 mg dose). The combination with semaglutide produced approximately double this effect, suggesting meaningful additive benefit from the two pathways. Monotherapy data is useful for researchers wanting to isolate the amylin receptor contribution versus the GLP-1R contribution in their study design.
What is the storage requirement for cagrilintide?
Lyophilized cagrilintide is stable at −20°C. Once reconstituted, store at 2–8°C and use within 30 days. The fatty acid modification makes the peptide prone to aggregation under mechanical stress — reconstitute by swirling gently rather than shaking.
Research Use Only
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