Cagrilintide — Long-Acting Amylin Analogue (Research Evidence Summary)

Discovery and characterisation

Cagrilintide (development code AM833 / NNC0174-0833) is a synthetic analogue of the pancreatic hormone amylin, engineered by Novo Nordisk with a lipid side chain that binds albumin in circulation and extends the plasma half-life from amylin's native minutes to roughly a week. It acts as a dual agonist at the amylin receptor (AMY1R/AMY3R heterodimers of the calcitonin receptor with RAMP subunits) and the calcitonin receptor itself.

Native human amylin is co-secreted with insulin from pancreatic β-cells and contributes to satiety and slowing of gastric emptying. Its pharmacological potential has been recognised since the 1980s, but native amylin's aggregation propensity and short half-life have historically limited it as a therapy. Pramlintide, an amylin analogue, is licensed as an adjunct to insulin in the US but not the UK. Cagrilintide's contribution is the once-weekly dosing profile that makes fixed-ratio combination with a once-weekly GLP-1 (semaglutide) clinically practical — the combination is what is being developed as CagriSema.

Evidence base

The published human evidence for cagrilintide as a monotherapy is limited to early-phase safety and PK studies. Its evidence base is dominated by combination studies with semaglutide.

Phase 1b (Enebo 2021, Lancet). Multiple ascending doses of cagrilintide plus semaglutide 2.4 mg were tolerated over 20 weeks in adults with overweight or obesity. The trial established that the combination did not produce unexpected PK interactions and set the basis for the fixed-ratio combination programme.

Phase 3 REDEFINE 1 (Garvey 2025, NEJM). In adults with overweight or obesity without type 2 diabetes, once-weekly CagriSema reduced body weight substantially compared with placebo over the trial period. The full data are in the primary publication.

Phase 3 REDEFINE 2 (Davies 2025, NEJM). In adults with overweight or obesity plus type 2 diabetes, CagriSema produced weight reduction alongside glycaemic improvement.

REDEFINE 1 blood-pressure sub-analysis (Verma 2026, Hypertension). A pre-specified analysis of the REDEFINE 1 population reporting the systolic and diastolic blood-pressure changes on CagriSema relative to placebo.

Phase 3 REIMAGINE 1-3 (Aroda / Buse / Rosenstock 2026, Lancet family). Extension of the CagriSema evidence base into type-2 diabetes populations: monotherapy-inadequate, versus components, and as an add-on to basal insulin.

Mechanism differentiation from GLP-1 monotherapy

The rationale for adding amylin agonism to GLP-1 agonism is that the two pathways converge on satiety and gastric emptying through partially independent central and peripheral routes. Amylin's satiety signal is mediated in part via area postrema and hindbrain circuits; GLP-1's includes vagal afferents and hypothalamic action. Combining a long-acting agonist for each is expected to produce additive rather than merely overlapping effects — a hypothesis the REDEFINE 1 outcomes appear to support numerically over head-to-head semaglutide-only comparators.

Whether the combination is meaningfully additive on hard endpoints beyond weight — cardiovascular outcomes, hepatic outcomes, renal outcomes — will require the corresponding outcome trials, which are not yet reported.

Regulatory and clinical status

UK status: Cagrilintide is not licensed by the MHRA as a standalone medicine. It has no product-authorisation route to prescription. As a component of CagriSema it is in phase 3 development; no marketing authorisation has been issued at the time of writing.

US and EU status: No FDA or EMA approval as of 2026-07. Investigational only.

Advertising implications in the UK: because cagrilintide is being investigated for weight-loss, and because it is not licensed, any UK-facing promotion that presents it as a weight-loss product would fall foul of the MHRA's rules on advertising unlicensed medicines. See our page on prescription-only medicine advertising and the GLP-1 advertising caution — the same framework applies.

Translational limitations

• Fixed-ratio combination. Cagrilintide's evidence base is inseparable from semaglutide's. Assertions about "cagrilintide alone" have essentially no phase-3 support.
• Duration. Even the phase-3 REDEFINE / REIMAGINE readouts are relatively short (68 weeks and less). Multi-year safety and effectiveness data — including on the durability of weight loss after cessation, muscle-mass changes, and cardiovascular outcomes — remain to be reported.
• Population. Trial populations exclude many groups (pregnancy, active cancer, severe renal or hepatic impairment); real-world generalisability requires post-authorisation study.

Related pages

• Semaglutide monograph — the GLP-1 arm of CagriSema
• Tirzepatide monograph — dual GIP/GLP-1 comparator class
• GLP-1 & Incretin Research Hub

Regulatory and clinical status

UK status: No standalone UK MHRA approval as of 2026-07. Investigational only; used almost exclusively in the CagriSema fixed-ratio combination programme with semaglutide. Not authorised for prescription or supply in the UK. Any weight-loss framing of cagrilintide in advertising falls under the POM-medicine advertising rules the MHRA applies to GLP-1s.

Read more about how UK regulation applies to peptides in our UK regulation hub and our explanation of what “research use only” means in the UK. PeptideStacks does not make editorial sourcing recommendations within research content; any vendor links elsewhere on this page appear in a clearly-labelled sponsor block (see our conflict-of-interest disclosure).

References

Peer-reviewed sources for the claims above. Where an editor has verified study type, sample size, outcome and limitation, the citation is rendered as a card; otherwise as a plain reference. Links open PubMed or the journal DOI.

1. Enebo LB, Berthelsen KK, Kankam M, et al.. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet (London, England). 2021;397(10286) :1736-1748 · PMID: 33894838
2. Garvey WT, Blüher M, et al.. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2025 · PMID: 40544433
3. Davies MJ, Bajaj HS, et al.. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine. 2025 · PMID: 40544432
4. Verma S, Böttcher M, et al.. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension (Dallas, Tex. : 1979). 2026 · PMID: 41328546
5. Aroda VR, Buzzetti R, et al.. Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study. The Lancet. Diabetes & Endocrinology. 2026 · PMID: 42251860
6. Buse JB, Bajaj HS, et al.. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. The Lancet. Diabetes & Endocrinology. 2026 · PMID: 42251859
7. Rosenstock J, Billings LK, et al.. Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet (London, England). 2026 · PMID: 42251856

Published: 2026-07-25Last updated: 2026-07-25Last reviewed: 2026-07-25

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