Amycretin

Amycretin fuses GLP-1 and amylin pharmacology into a single acylated peptide, so the two satiety pathways are engaged in fixed proportion with a single pharmacokinetic profile rather than two. Mechanistically it is the same logic as CagriSema - GLP-1 receptor agonism for delayed gastric emptying and reduced food reward, amylin receptor agonism in the area postrema for meal termination - with the practical advantage of one molecule, one titration and no co-formulation stability problem. Both a once-weekly subcutaneous and a once-daily oral formulation exist, which is unusual for a peptide of this size and reflects Novo's SNAC absorption-enhancer platform.

Targets: GLP-1 receptor, Amylin receptors, Calcitonin receptor

• · Escalating weekly doses over 36 weeks produced about 22% mean weight loss at the highest arm. Published dose arms have been reported inconsistently in secondary sources, so no milligram figure is stated here.
• · A 12-week oral study produced about 13.1% weight loss. Doses have been described as escalating into the tens of milligrams daily but are not reliably documented publicly.

Work out your exact syringe units →

• very commonNausea— Dose-dependent, consistent with the GLP-1 arm.
• very commonDecreased appetite— Strong enough that undereating protein is a genuine risk.
• commonVomiting
• commonLoss of lean mass— Expected at this rate of weight loss, though the amylin arm may mitigate it.

• Pregnancy.
• History of pancreatitis - class caution.
• Long-term safety is unknown; phase 3 has only just begun.

• redundantsemaglutide — GLP-1 agonism is already built in.
• redundantcagrilintide — Amylin agonism is already built in.
• cautioninsulin-analogues — Hypoglycaemia risk in combination.

• · Weight and body composition.
• · Protein intake.
• · HbA1c.

Investigational; not approved anywhere. No legitimate consumer supply exists.

• Amycretin phase 1b/2a subcutaneous and oral results, The Lancet 2025 (trial)
• Novo Nordisk 2025-2026, amycretin phase 3 programme announcements (other)

Amycretin is CagriSema's thesis compressed into one molecule. Instead of co-formulating an amylin analogue with a GLP-1 analogue, Novo built a single peptide that agonises both receptor systems, which solves several problems at once: one manufacturing process instead of two, guaranteed 1:1 exposure at every site of action rather than two molecules distributing independently, and the ability to tune the ratio structurally rather than by mixing. Since the two pathways are pharmacologically independent - GLP-1 receptors for appetite suppression, calcitonin-receptor-plus-RAMP complexes for satiation - the satiety effects add while the nausea does not add proportionally, which is what allows the aggressive early weight-loss curve. And it is aggressive: roughly 22% at 36 weeks subcutaneously in a phase 1b/2a study, which is the steepest reported trajectory in the field, and 13.1% at 12 weeks orally. The caveats are proportionally large. These are early-phase studies with small numbers, no plateau had been reached so the 36-week figure is not a ceiling, and early-phase weight-loss curves in this field have historically flattened when trials got longer and populations got broader. Phase 3 began in 2026. There is a specific technical achievement worth noting: getting a dual-receptor peptide to work orally at all is difficult, because oral peptide delivery depends on an absorption enhancer creating a narrow window in the stomach and the molecule surviving it - the fact that the oral form produced 13.1% in 12 weeks is arguably more impressive than the injectable number.

No consumer supply exists, and grey-market vials labelled amycretin cannot be what they claim - this is a proprietary unimolecular co-agonist that only Novo makes. The scientific caution is the standard one for early-phase obesity data: a 22% figure from a phase 1b/2a study with small numbers and no plateau is a hypothesis about what phase 3 will show, not a result you can rely on. Historically, obesity weight-loss curves flatten when trial populations broaden.

• GLP-1 receptor (GLP1R) — Not verified

  Appetite suppression, delayed gastric emptying, glucose-dependent insulin secretion, glucagon suppression.

• Amylin receptors (AMY1R, AMY2R, AMY3R) — Not verified

  Meal-terminating satiation via the area postrema, additional gastric-emptying delay, and the amylin class's apparent lean-mass-sparing effect.

• Amycretin subcutaneous phase 1b/2a Phase 1b/2a · 36 weeks · 2025

  Approximately 22% mean weight reduction at 36 weeks with no plateau reached.

• Amycretin first-in-human phase 1 Phase 1 · 2025

  Safety, tolerability, pharmacokinetics and pharmacodynamics of the first GLP-1 and amylin receptor co-agonist in humans.

Weight loss was rapid from the first weeks and had not plateaued at 36 weeks in the subcutaneous study. The oral form produced 13.1% at 12 weeks, which is an unusually steep early trajectory for an oral agent.

Amycretin already contains both mechanisms, so cagrilintide, petrelintide, semaglutide and every other GLP-1 or amylin agent is redundant with it. Adding tirzepatide or retatrutide would layer a second incretin arm and only adds side effects. There is no legitimate supply, so this is theoretical. If it reaches market, the interesting question will be whether adding GIP on top - the one mechanism it does not have - is worth anything.

Against CagriSema: the same two mechanisms in one molecule instead of two, with a steeper early curve in far weaker studies. Against retatrutide: comparable early numbers from entirely different mechanisms - amycretin uses GLP-1 plus amylin with no glucagon arm, so it should not carry retatrutide's heart-rate and fasting-glucose problems. Against tirzepatide: amycretin's early data look better, but the comparison is a phase 1b/2a study against a completed phase 3 programme, which is not a comparison at all.

Investigational; no legitimate supply and no price.

• ?No verified pharmacokinetic parameters despite published phase 1 papers - the values were not extracted in this session.
• ?Participant numbers, dose levels and titration schedules were not extracted.
• ?The 22% and 13.1% figures come from early-phase studies with small samples and no plateau; they should not be treated as phase 3 predictions.
• ?Sequence and structure are proprietary and unverified.
• ?Whether the oral formulation's exposure is reliable enough for real-world use is not established.

• Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study Dahl K et al., Lancet, 2025 · PMID 40550231

  The 36-week subcutaneous weight-loss data - the steepest curve reported in the field.

• Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial Gasiorek A et al., Lancet, 2025 · PMID 40550229

  First-in-human pharmacology and the source for dose-escalation and tolerability observations.