Cagrilintide
Long-acting amylin analogue — the satiation arm the incretins leave untouched.
Metabolic · 9 min read · updated 17 Aug 2026
Research use only. The ranges below are what published studies and community protocols report. They are reference material for laboratory research, not medical advice or a recommendation for human or veterinary use.
The compound
Cagrilintide
View- Type
- Amylin Analog / Amylin & Calcitonin Receptor Agonist
- CAS
- 1415456-99-3
- Formula
- C₁₉₄H₃₁₂N₅₄O₅₉S₂
- Mass
- ~4409.0 Da
At a glance
- Class
- Long-acting amylin analogue (amylin + calcitonin receptor agonist)
- Also known as
- AM833
- Length
- 37 amino acids (amylin backbone)
- Molecular weight
- ~4409.0 Da
- CAS
- 1415456-99-3
- Half-life
- ~7–8 days (albumin-bound)
- Cadence studied
- Once weekly
- Development stage
- Investigational — no standalone approval anywhere
- Vial size stocked
- 5 mg (single format)
Cagrilintide is a long-acting analogue of human amylin, the 37-amino-acid peptide co-secreted with insulin by pancreatic β-cells. Amylin is the second β-cell hormone and it has been understood for decades, but it has never been an easy molecule to work with. Native human amylin is cleared within minutes, and it is amyloidogenic — it self-associates into the islet amyloid fibrils that gave the peptide its other name, islet amyloid polypeptide. Any usable analogue has to solve both problems at once.
Pramlintide, the first-generation analogue, solved the aggregation half. Proline substitutions borrowed from a non-fibrillating rodent sequence stopped it forming fibrils, but it did nothing for clearance — pramlintide's half-life is under an hour, so it had to be given before every meal. Cagrilintide solves both. Substitutions across the aggregation-prone region keep it in solution, and a C20 eicosanedioic diacid attached at the N-terminus through a γ-glutamic acid linker gives reversible albumin binding — the same albumin-binding strategy Novo Nordisk used on semaglutide, though semaglutide hangs its diacid off the Lys26 side chain rather than off the peptide N-terminus. The result is a peptide with a terminal half-life around seven to eight days and a once-weekly cadence.
Its receptor profile is worth being precise about, because it is where cagrilintide and the newer amylin compounds diverge. There is no standalone "amylin receptor" gene. Amylin receptors are heteromers: the calcitonin receptor in complex with one of three receptor activity-modifying proteins, giving AMY1, AMY2 and AMY3. Cagrilintide is non-selective across that family and also activates the bare calcitonin receptor, which is why the literature often describes it as a dual amylin and calcitonin receptor agonist rather than a pure amylin agonist.
The investigational thesis behind the molecule is not that it beats a GLP-1 agonist. It is that it works through a different receptor family entirely, so its effect adds to an incretin rather than duplicating it. Almost all of the late-stage work on cagrilintide has been on that pairing rather than on the compound alone.
It is an investigational compound. Cagrilintide has no standalone approval in any jurisdiction; the fixed-dose combination with semaglutide is the formulation that has been through phase 3, and its regulatory status has been moving — verify it currently rather than trusting a dated article.
Mechanism in detail
Amylin receptors are class B G-protein-coupled receptors in the same structural family as the GLP-1 receptor, but they are different genes with different tissue distributions, and there is no cross-activation between the two. The downstream signal is again Gs-coupled and cAMP-driven; what differs is where the receptors sit.
- Area postrema: the primary central target. The area postrema is a circumventricular organ without a complete blood–brain barrier, so a circulating amylin analogue reaches it directly rather than having to cross into the parenchyma. Activation there terminates the meal in progress — the measurable effect is on meal size, not on how often a meal is initiated.
- Stomach: gastric emptying slows, as it does with GLP-1 agonism, though the afferent route differs. This contributes to post-prandial glucose flattening and is part of the early nausea signal.
- Pancreatic α-cell: post-prandial glucagon secretion is suppressed. This is the effect the first-generation analogue was approved on, and it is glucose-context dependent rather than absolute.
- Leptin signalling: amylin agonism restores leptin responsiveness in diet-induced obesity models, which is unusual — most interventions do not. It is the mechanistic basis for describing amylin as acting on the defended body-weight set point rather than only on appetite in the moment.
- Calcitonin receptor: cagrilintide's non-selectivity means this arm is engaged too. Calcitonin receptors are expressed centrally and on osteoclasts. The central contribution plausibly adds to the satiation effect; the skeletal contribution is the part of the profile with the least long-term data behind it.
Why it is paired with a GLP-1 agonist rather than escalated alone
- Non-overlapping receptors. Adding cagrilintide to semaglutide is not the same as raising the semaglutide dose — the second compound engages a receptor family the first does not touch, so the effects are additive rather than a steeper climb up one dose–response curve.
- Different behavioural targets. GLP-1 agonism reduces both meal size and the drive to eat between meals; amylin agonism acts predominantly on meal termination. The two shape intake through different levers.
- Tolerability headroom. Pushing a single incretin higher buys effect at a rising gastrointestinal cost. The combination trials were designed on the premise that splitting the load across two mechanisms reaches further before tolerability becomes the constraint.
- No expenditure arm. Unlike retatrutide's glucagon component, amylin agonism has no documented effect on energy expenditure. Cagrilintide is an intake-side compound, and reading it as a metabolic-rate intervention is a category error.
What the research literature covers
This list is short, and it is short honestly. There is no cagrilintide equivalent of the STEP or SURPASS programmes — the published record is a handful of trials, only one of which is a monotherapy dose-finding study.
- Lau DCW et al., Lancet 2021 — the phase 2 dose-finding trial. Once-weekly cagrilintide at 0.3, 0.6, 1.2, 2.4 and 4.5 mg over 26 weeks, against both placebo and liraglutide 3.0 mg as an active comparator. Essentially every monotherapy dose figure in circulation traces back to this trial.
- Enebo LB et al., Lancet 2021 — the phase 1b co-administration study, cagrilintide escalated alongside semaglutide 2.4 mg over 20 weeks. This is where the combination came from.
- Frías JP et al., Lancet 2023 — phase 2 of the fixed 2.4 mg + 2.4 mg combination in type 2 diabetes.
- The REDEFINE programme — phase 3 of the fixed-dose combination, in obesity and in type 2 diabetes. This is the late-stage evidence base, and it is evidence about the combination, not about cagrilintide alone.
- Kruse T et al., J Med Chem 2021 — the medicinal chemistry: how the analogue was made both non-fibrillating and long-acting.
Reading the dose ladder — and why it is short
Every monotherapy dose worth quoting comes from one trial. Lau et al. randomised subjects to five fixed weekly levels and escalated into them over the opening weeks rather than starting at target, the same tolerability logic the incretin programmes use. 4.5 mg weekly is the highest dose with published 26-week data, and nothing above it has been reported.
The 2.4 mg figure has a different provenance from the rest, and it is routinely misread. It is not a monotherapy optimum — it is the level fixed for the semaglutide pairing, chosen to sit alongside semaglutide 2.4 mg. In the dose-finding trial the response had not flattened by 4.5 mg, so 2.4 mg is best understood as the combination dose rather than as "the" cagrilintide dose.
That leaves a genuinely thin protocol picture, and this article does not thicken it. Community dosing material for cagrilintide is largely reconstructed from those same two numbers rather than from independent reporting, so the table below gives trial arms and trial durations and stops there. A week-by-week ladder of the kind the semaglutide article carries would be partly invented, and it is not offered here.
Cagrilintide and Eloralintide, compared
Both compounds act on the amylin pathway and this catalogue stocks both, so the comparison gets asked. Both now have published phase 2 monotherapy data, so the useful comparison is not one of characterisation but of receptor selectivity and of how far each programme has run.
- Cagrilintide: a 37-amino-acid pramlintide-like backbone, CAS 1415456-99-3, ~4409 Da, and a 26-week phase 2 monotherapy dose-finding trial at 0.3–4.5 mg weekly, followed by a phase 3 programme whose pivotal obesity and type 2 diabetes trials have completed and been published, with the cardiovascular outcomes trial still running — though that phase 3 work tested the fixed-dose combination with semaglutide rather than the compound alone. Non-selective: AMY1–3 plus the bare calcitonin receptor.
- Eloralintide (LY-3841136): a selective amylin receptor agonist from Eli Lilly, CAS 2883634-40-8, ~4526 Da, with the full sequence disclosed in US patent application 2022/0288168 A1. Its phase 2 was a 48-week, multicentre, double-blind, placebo-controlled monotherapy trial (NCT06230523) in 263 adults with obesity or overweight plus at least one weight-related comorbidity and without type 2 diabetes — 1, 3, 6 and 9 mg once weekly, alongside arms escalating stepwise up to 9 mg. Every arm beat placebo, with mean weight reduction running from 9.5% to 20.1% against 0.4% on placebo and rising with dose. Adverse events were mostly mild-to-moderate gastrointestinal symptoms and fatigue, less frequent with slower escalation. Still investigational, with no approval anywhere.
- The question that actually separates them — whether amylin-receptor selectivity is better than dual amylin/calcitonin agonism — is open. Selectivity may avoid calcitonin-arm effects nobody wants; the calcitonin arm may also be contributing to the effect that makes cagrilintide work. No head-to-head trial in humans has been run, so the two records sit side by side in different populations rather than against each other.
- The practical consequence: both dose tables are trial arms rather than community ladders, and they do not convert into one another. Cagrilintide was escalated to 4.5 mg over 26 weeks, eloralintide to 9 mg over 48 weeks, at different potencies against a partly different receptor set — reading a milligram figure across from one compound to the other is guessing.
Storage
- Lyophilised powder: 2–8 °C, or −20 °C if the vial will sit for more than a few months. Protect from light.
- Reconstituted: 2–8 °C, protected from light, used within roughly 28–30 days. Never freeze — beyond the usual shearing damage, a freeze–thaw cycle is the classic trigger for aggregation in this peptide family.
- Malaysian ambient conditions are the practical constraint. The lyophilised powder tolerates a shipping excursion of a day or two; a reconstituted vial left out on a bench does not.
Cautions
- Investigational compound. Cagrilintide has no standalone approval in any jurisdiction, and the long-term safety record that exists for semaglutide does not exist for this molecule.
- Nausea and vomiting dominate the reported adverse-event profile and scale with dose. Gastrointestinal effects were the main dose-limiting finding in the phase 2 monotherapy trial.
- Amylin analogues suppress glucagon and delay gastric emptying. The first-generation analogue, pramlintide, carries a boxed warning for severe hypoglycaemia when co-administered with insulin — the class hazard is insulin co-exposure rather than amylin agonism on its own, and it is the interaction most worth knowing about.
- Delayed gastric emptying alters the absorption kinetics of anything given orally in the same model.
- Cagrilintide also agonises the calcitonin receptor. Calcitonin signalling has skeletal effects, and long-term skeletal data for chronic non-selective amylin/calcitonin agonism do not exist.
References & credit
- 1Lau DCW et al., Lancet 2021 — Phase 2 dose-finding — once-weekly cagrilintide 0.3–4.5 mg over 26 weeks against placebo and liraglutide 3.0 mg. The source of the monotherapy rows above.
- 2Enebo LB et al., Lancet 2021 — Phase 1b — cagrilintide co-administered with semaglutide 2.4 mg, the study the fixed-dose combination grew out of.
- 3Frías JP et al., Lancet 2023 — Phase 2 of the fixed 2.4 mg + 2.4 mg combination in type 2 diabetes.
- 4Kruse T et al., J Med Chem 2021 — Development of cagrilintide — the chemistry behind the non-fibrillating, albumin-binding design described above.
- 5Roth JD et al., PNAS 2008 — Amylin agonism and restored leptin responsiveness in diet-induced obesity — the basis for the set-point framing above.
- 6REDEFINE programme, Novo Nordisk — Phase 3 trials of the fixed-dose cagrilintide + semaglutide combination in obesity and in type 2 diabetes. Reported from 2024 onward; confirm the current publication and regulatory status rather than relying on a dated article.
This article was written in-house. Where a dose range reflects community practice rather than a published trial, the community references we consulted are credited above and the article says which is which.