Amycretin
Amylin / GLP-1 unimolecular
Amycretin (Amylin / GLP-1 unimolecular) is a metabolic & fat loss research compound. Single molecule hitting both amylin and GLP-1 receptors — additive appetite suppression via different brain circuits; oral and injectable forms.
Amycretin quick facts
| Reported research dose | 1.25mg-20mg weekly (subq) |
| Route | Subq |
| Frequency | or Weekly (subq) |
| Half-life | Form-dependent (oral vs subq) |
| Forms | Injectable |
| Evidence level | Phase 1/2 human (~10-13% in 12 wks) |
Amylin + GLP-1 in one — the early numbers are eye-popping. Very new.
How Amycretin works
Single molecule hitting both amylin and GLP-1 receptors — additive appetite suppression via different brain circuits; oral and injectable forms.
Proposed benefits
Researched for fat oxidation, appetite and energy regulation, insulin sensitivity and endurance capacity.
Where to get Amycretin
See vetted vendors for Amycretin →Bacteriostatic water is the diluent — sterile water with 0.9% benzyl alcohol, which is what lets a vial be drawn from more than once. It does not come with the vial, and unlike the compound it is bought again every time.
Need bacteriostatic water? Get it at AminoWell USA (my company) → Code CAMERON.
The evidence for Amycretin
Graded by what exists behind each claim.
✅ Clinically validated
- In phase 3 as of 2025. Novo Nordisk's single-molecule GLP-1 and amylin co-agonist. Early phase 1/2 results generated unusual attention: the subcutaneous form reported around 22% weight loss at 36 weeks, and an oral form showed roughly 13% at 12 weeks.
- These are early, small, dose-escalating studies. Phase 1 weight numbers have repeatedly failed to hold at phase 3 scale across this entire field, so the figure to watch is the phase 3 readout, not the headline.
📊 Correlative data
- No real-world use at all. Trial reports describe class-typical GI effects, which appear more pronounced at the higher doses driving the headline numbers.
🧪 Theoretical / extrapolated
- One molecule hitting two receptors — GLP-1 and the amylin receptor — rather than co-formulating two drugs as CagriSema does.
- Amylin and GLP-1 suppress appetite through genuinely separate pathways: GLP-1 acts largely on hypothalamic and hindbrain circuits, amylin on the area postrema. Hitting both is additive rather than redundant, which is the mechanistic case for the larger effect size.
- A single molecule also means one pharmacokinetic profile to manage instead of two, which is a real formulation advantage if the ratio is right.
How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →
What Amycretin actually does
Amycretin is one molecule that activates the GLP-1 receptor and the amylin receptor, and the published preclinical work says it activates a third one that nobody mentions. In cell-based systems it activated human, mouse and rat GLP-1, amylin AND calcitonin receptors Kuhre 2025. The calcitonin receptor is not a footnote here, for a reason that is structural rather than incidental.
There is no such gene as ‘the amylin receptor’. An amylin receptor is the calcitonin receptor (CTR) with a receptor-activity-modifying protein bolted onto it: CTR plus RAMP1 is AMY1, plus RAMP2 is AMY2, plus RAMP3 is AMY3. The same seven-transmembrane protein, three different accessory subunits, four different pharmacologies. Cryo-EM structures of the closely related cagrilintide bound to AMY1R, AMY2R, AMY3R and CTR in the Gs-coupled active state show an amylin-like binding mode across all of them Cao 2025, and a parallel structural study describes a shared ‘bypass’ binding mode that enables non-specific binding and activation across different receptors Gu 2025.
So the selectivity question for this drug is not GLP-1 versus amylin. It is AMY versus CTR. A molecule that hits bare CTR as well as CTR+RAMP is doing calcitonin pharmacology — suppressing osteoclasts and lowering serum calcium — alongside the appetite pharmacology it is sold for. That is the ratio that decides what else this compound does to a person, and no potency numbers of any kind have been published for amycretin at any of the three receptors. Not in the first-in-human paper, not in the subcutaneous phase 1b/2a, not in the rodent paper Gasiorek 2025 Dahl 2025 Kuhre 2025.
Why combining the two axes is a real idea rather than a marketing one. GLP-1 receptor agonism suppresses intake through the hindbrain and hypothalamus and slows gastric emptying. Amylin signals meal-related satiation through the area postrema and, distinctively, appears to reset the defended body weight rather than only opposing intake. In diet-induced obese rats, amycretin cut total energy intake by 47% over 21 days while maintaining energy expenditure Kuhre 2025. Maintained expenditure during a 47% intake cut is the interesting half: the usual metabolic response to that deficit is adaptive thermogenesis downward.
The thing that makes this compound unusual in this catalog: it exists as a tablet and as an injection, and they are the same molecule. A peptide given orally at up to 2 × 50 mg once daily Gasiorek 2025 and subcutaneously at 0.3 to 60 mg once weekly Dahl 2025 is being asked to survive two completely different journeys, and the dose numbers are the only public evidence of what that costs.
Cell, rodent, human — and where it stops
Step one, in cells. Human, mouse and rat GLP-1, amylin and calcitonin receptors, all activated Kuhre 2025. No potency values in the abstract.
Step two, in rats and mice. Diet-induced obese rats, 21 days: total energy intake down 47% (95% CI for the mean, vehicle 2,132–2,493 kcal against amycretin 1,044–1,390), body weight down 18% relative to vehicle (vehicle +6.56 to +8.47%, amycretin −10.48 to −12.74%, P < 0.0001), energy expenditure maintained. Insulin sensitivity improved on a hyperinsulinemic euglycemic clamp — higher glucose infusion rate than vehicle — and hepatic steatosis improved histologically. Labeled compound reached the mouse brain areas that regulate food intake Kuhre 2025.
Step three, humans, oral, and read the endpoint before the number. A first-in-human phase 1 at a single research unit in San Antonio, Texas, in adults aged 18 to 55 with a BMI of 25.0–34.9 (parts A and B) or 27.0–39.9 (part C/D), NCT05369390. Part A: single oral doses of 1, 3, 6, 12, 18 and 25 mg, 48 participants. Part B: 3, 6 or 12 mg once daily for 10 days, 36 participants. Part C/D: 60 participants on 12-week fixed titrations to 50 mg, to 2 × 50 mg, or to 2 × 25 mg once daily. The primary endpoint was the number of treatment-emergent adverse events Gasiorek 2025.
It met that endpoint in the sense such a trial can: 364 events in 89 of 144 participants (62%), all mild or moderate, rising with dose; 180 (49%) gastrointestinal, occurring in 72 (81%) of those who had any event; no deaths; plasma concentrations dose-proportional across every group. Body weight was an exploratory endpoint and the abstract does not state the percentage Gasiorek 2025. This site’s card carries ‘~10-13% in 12 wks’. That figure comes from the sponsor’s own presentation of the same study, not from the trial publication, and it is an exploratory read-out of a safety trial either way.
Step four, humans, subcutaneous, and the largest weight number in this whole catalog. A phase 1b/2a, again at a single center in San Antonio, ages 18–55, BMI 27.0–39.9, NCT06064006. 125 participants: 101 on amycretin, 24 on placebo, split across five parts. Mean baseline weight 88.3–99.1 kg. Escalations: Part B from 0.3 mg to 60 mg over 36 weeks; Part C to 20 mg over 36 weeks; Part D to 5 mg over 28 weeks; Part E to 1.25 mg over 20 weeks. The primary endpoint was, again, the number of treatment-emergent adverse events. Weight was secondary: −24.3% versus −1.1% at week 36 (60 mg), −22.0% versus +1.9% at week 36 (20 mg), −16.2% versus +2.3% at week 28 (5 mg), and −9.7% versus +2.0% at week 20 (1.25 mg), P < 0.0001 for parts A–D and P = 0.0003 for part E Dahl 2025.
And the sentence in the same abstract that most people skip: ‘a large number of participants withdrew from the study, with a high proportion of discontinuations occurring due to reasons unrelated to treatment-emergent adverse events’ Dahl 2025. A −24.3% figure produced in a dose-escalation part of a phase 1b, at one site, with heavy attrition, spread across 24 placebo recipients in total for all five parts, is a real result and it is not the same kind of object as a 3,000-person phase 3.
The obstacles, one at a time. (1) Both human trials had a safety count as the primary endpoint; every weight number quoted for this compound is a secondary or exploratory read-out Gasiorek 2025 Dahl 2025. (2) Both were single-site, and both excluded anyone over 55. There is no data in the age group most likely to have metabolic disease. (3) No potency ratio at any of the three receptors it activates Kuhre 2025. (4) No published oral bioavailability, so the tablet and the injection cannot be compared on delivered drug. (5) No body composition at any dose, including the −24.3% arm. (6) No phase 3 result in the indexed literature at the time this page was written.
Amycretin pharmacokinetics — how much of it actually gets in
The card says ‘Form-dependent (oral vs subq)’, which is unusually honest and is where the thinking normally stops. Here is the arithmetic behind it.
The two routes, in administered milligrams per week. Orally, the top regimen was 2 × 50 mg once daily Gasiorek 2025 — 700 mg a week. Subcutaneously, the arms ran from 1.25 mg to 60 mg once weekly Dahl 2025. So the same molecule is given at between 12 and 560 times more material by mouth than by needle. That ratio is not a fact about potency; it is the price of the gut, and it is the only public quantity that bounds this peptide’s oral bioavailability. No absolute bioavailability figure has been published for amycretin by either route.
What degrades it, and where. Swallowed, a peptide meets gastric acid, then pancreatic proteases, then brush-border peptidases, then hepatic first-pass extraction. Injected, it skips all four and faces plasma and tissue peptidases only. Dipeptidyl peptidase-4 cleaves the GLP-1 N-terminus at position 2 unless that residue is protected, which is the standard modification in this class and is why a native GLP-1 lasts minutes.
What holds it in the body. Once-weekly subcutaneous dosing at 36 weeks of continuous escalation Dahl 2025 implies reversible albumin binding through an acyl side chain, the same principle every weekly peptide in this catalog uses, and a half-life on the order of 5 to 7 days: steady state on a weekly schedule takes four to five half-lives, which is why these escalations are stepped in weeks rather than days. The oral form is dosed once daily and its plasma concentrations were dose-proportional across every group Gasiorek 2025, which says absorption rather than elimination is what limits it.
Why the two forms are not interchangeable at any dose. A daily tablet produces a peak-and-trough profile inside 24 hours; a weekly injection produces a nearly flat one. For a drug whose dose-limiting effect is nausea — 49% of all adverse events in the oral study were gastrointestinal Gasiorek 2025 — peak height is the variable that matters, and it differs between the two forms by more than the milligram numbers suggest. Anyone converting between them on a milligram basis is converting the wrong quantity.
What would have to be true, and how you would know it was not
Four predictions. The third one argues against the headline number on this page.
1. Fasting insulin should fall further than the weight loss alone would explain. In DIO rats, amycretin improved insulin sensitivity on a hyperinsulinemic euglycemic clamp — the reference method, not a surrogate — while energy expenditure was maintained Kuhre 2025. Draw fasting insulin and HbA1c at baseline, 12 and 24 weeks. Weight-matched comparisons are what would prove this, and nobody has run one; in one person the workable version is to plot fasting insulin against kilograms lost and look for a steeper slope than a previous diet-only attempt produced.
2. Serum calcium is the marker this compound’s own pharmacology asks for and nobody orders. Amycretin activates the calcitonin receptor Kuhre 2025, and calcitonin’s defining physiological action is lowering serum calcium by suppressing osteoclasts. A CMP already contains calcium, so this costs nothing to add. The prediction is a small fall or no change; a measurable fall would be the first human evidence that the calcitonin arm of this molecule is engaged at the doses people use.
3. Lean mass will not be spared at the top dose, and this cuts against the compound. The −24.3% arm has no published body composition of any kind Dahl 2025. Measure grip strength at baseline, 12, 24 and 36 weeks with the same dynamometer at the same time of day. A 24% weight loss in a 95 kg person is roughly 23 kg; if even a quarter of that is fat-free mass, that is nearly 6 kg of it, and grip strength is the cheapest instrument that would notice.
4. The route check, which is decisive and free. The published oral doses run to 100 mg a day and the published subcutaneous doses start at 1.25 mg a week Gasiorek 2025 Dahl 2025. Any product sold as ‘oral amycretin’ at microgram or single-milligram strengths is offering, by mouth, a dose two to three orders of magnitude below the smallest one ever studied by that route. That is arithmetic, not opinion, and it does not require a blood test.
What nobody has tested yet
Five experiments, and the first is the one that would change what this drug is understood to be.
1. Nobody has published the three-receptor potency ratio. Amycretin activates GLP-1, amylin and calcitonin receptors in three species Kuhre 2025 and not one EC50 appears in any of the three papers. Because an amylin receptor is CTR plus a RAMP Cao 2025, the number that matters is the AMY-to-bare-CTR margin, and it is unknown. One published cAMP panel would settle whether this is an amylin drug with calcitonin spillover or a calcitonin drug wearing an amylin coat.
2. Nobody has measured its absolute oral bioavailability. The same molecule is given at 700 mg a week by mouth and as little as 1.25 mg a week by needle Gasiorek 2025 Dahl 2025. A single radiolabelled cross-over study — the design already published for the oral small molecule beside it in this catalog — would produce the number and it has not been done for any oral peptide in this class.
3. Nobody has looked at bone. Chronic calcitonin receptor agonism suppresses osteoclasts; a related non-erythropoietic peptide in this same Vault raised murine bone mineral density by about 5% in a month on exactly that logic Awida 2021. Whether 36 weeks of amycretin changes bone turnover markers or density in either direction is completely unstudied, and it is the kind of question that only gets asked after a drug is widely used.
4. Nobody has compared oral against subcutaneous at matched exposure. Two trials, two routes, two different sets of participants, no cross-over Gasiorek 2025 Dahl 2025. Whether the flat weekly profile or the daily peak-and-trough produces less nausea for the same weight loss is the single most useful question for anybody choosing between the forms, and it has never been asked.
5. Nobody has given it to anyone over 55. Both human trials capped enrolment at 55 years Gasiorek 2025 Dahl 2025. Amylin signaling runs through the area postrema, gastric emptying slows with age, and the population with the most metabolic disease is older than every participant studied so far.
Amycretin — its own safety story, not its class's
The class block on this page is written for GLP-1 receptor agonists. Five things here belong to amycretin specifically.
1. The dropout is the finding. The subcutaneous study reports in its own abstract that a large number of participants withdrew, with a high proportion of discontinuations unrelated to adverse events Dahl 2025. That phrasing protects the safety read-out and it also means the −24.3% figure describes whoever was still there at week 36. Completer-based percentages from an escalation cohort are the most flattering number a trial can produce, and this is one.
2. The gastrointestinal load, sized properly. Orally: 364 treatment-emergent events in 89 of 144 participants, 180 of them (49%) gastrointestinal, occurring in 81% of everyone who had any event, rising with dose Gasiorek 2025. Subcutaneously: gastrointestinal events were the most common, mostly mild to moderate, and mostly resolved Dahl 2025. Nothing here is novel for the class; what is specific is that the frequency scaled with dose in a study whose top oral dose was 100 mg a day.
3. The calcitonin receptor is this molecule’s own open question. Amycretin activates it Kuhre 2025, and no human trial has reported serum calcium, bone turnover markers or bone density. Salmon calcitonin, given chronically, carried enough of a signal to change its label. That is a different molecule at a different receptor occupancy and the analogy is not proof — it is the reason the question belongs on this page rather than nowhere.
4. What the safety database actually is. 269 people across both trials, one clinical research site, everybody aged 18 to 55, longest exposure 36 weeks, total placebo exposure 24 people in the subcutaneous study Gasiorek 2025 Dahl 2025. For comparison, the drug this one is meant to succeed has cardiovascular outcome data in tens of thousands. Amycretin is early-phase, and early-phase is a description of how much is unknown rather than a stage of approval.
5. And the specific research-market risk. One name now covers an oral tablet and a subcutaneous injection with a 12-to-560-fold difference in weekly milligrams. Vials sold under this name carry no route on them. Somebody injecting a dose derived from the oral trial numbers would be giving between one and two orders of magnitude more drug than any subcutaneous arm ever received, and the dose-limiting toxicity of this class is vomiting.
Sources read for this page
- Gasiorek A, et al. 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. The Lancet 2025 · PMID 40550229
- Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. The Lancet 2025 · PMID 40550231
- Kuhre RE, et al. The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats. EBioMedicine 2025 · PMID 40706446
- Cao J, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications 2025 · PMID 40204768
- Gu YM, et al. Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors. Acta Pharmacologica Sinica 2025 · PMID 40847076
- Awida Z, et al. The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice. International Journal of Molecular Sciences 2021 · PMID 35008482
Amycretin — safety, predicted from mechanism
Predicted from mechanism, not from a human safety trial. How that reasoning works →
What the mechanism predicts
Derived from the molecule, not a trial.
- These slow gastric emptying and act on hypothalamic and brainstem appetite centers. Almost everything that goes wrong follows from the gastric emptying, not from anything exotic: nausea, early fullness, reflux, constipation, and — when someone titrates faster than their gut adapts — vomiting.
- The composition risk is the one nobody warns about. Appetite suppression does not discriminate. It suppresses the appetite for protein too, and in a deficit without adequate protein and a resistance stimulus a meaningful share of the loss is lean mass. That lowers the maintenance intake you eventually eat back into, which is the mechanism behind most of the rebound stories.
- Slowed emptying also delays absorption of anything else taken by mouth — a pharmacokinetic consequence rather than a drug interaction, but it matters for anything time-critical.
What has actually been reported
- GI effects are extremely common and mostly settle over weeks. Gallbladder problems are a recognized signal, and rapid weight loss of any cause raises gallstone risk — the drug is not doing something unusual, it is doing rapid weight loss well.
- Pancreatitis is reported and rare. The presentation to know is severe upper abdominal pain radiating to the back, usually with vomiting.
- A thyroid C-cell tumor signal exists in rodents and has not been demonstrated in humans; it is why the labeled contraindication for medullary thyroid carcinoma and MEN2 exists.
How to reduce the risk
Same mechanism as the prediction.
- Follow the titration schedule even if you feel fine. It exists for gut adaptation, not for legal cover. Almost everyone who quits in the first month escalated faster than their stomach could keep up.
- Hit your protein target first at every meal, before anything else on the plate. This is the single highest-leverage habit on the drug — 1.6–2.2 g/kg, and eat it while you still have the appetite to.
- Lift while you are on it. The compound handles intake; resistance training is the only thing handling what you keep.
- Aim for 0.5–1% of bodyweight per week, deliberately. The drug removes the hunger signal that would normally stop you going too hard, so the rate has to be a decision rather than a by-product.
- Fiber and electrolytes from day one, not from week four when constipation has already made up your mind about the drug.
- If nausea is winning, step back one dose rather than quitting the class. Almost nobody needs to be at the top of the range.
What it does to your bloodwork
A fact about the assay.
- HbA1c and fasting glucose should improve — that is the drug working, and it is the cleanest confirmation you have.
- Rapid loss moves lipids, liver enzymes and uric acid transiently. A wobble at 8 weeks into aggressive loss is usually the loss, not a new problem — but it is a reason to have the baseline.
- Worth a thyroid panel and a lipid panel before starting, simply so a later result has something to be compared against.
Don't run this if
- Personal or family history of medullary thyroid carcinoma, or MEN2.
- Previous pancreatitis.
- Active gastroparesis — you would be adding a drug whose main action is the thing already wrong.
The honest unknown
- What happens to body composition over repeated multi-year cycles of loss and regain on and off these drugs. Weight is well studied; the muscle-to-fat ratio of what comes back is not.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this with a pharmacist or doctor.
Amycretin — interference & stacking
Predicted from mechanism, not from an interaction study. How mechanism-predicted claims are made →
What Amycretin moves on your bloodwork
Expected direction, not a measured one.
- HbA1c (Hemoglobin A1c) — ↓ expected to fall
Falling HbA1c is the compound working. Expect it.
What to do: Baseline and 12 weeks. It moves slowly by design — a 4-week retest tells you very little. - Fasting Insulin — ↓ expected to fall
Insulin sensitivity improves as weight falls and the incretin effect restores first-phase insulin release.
What to do: Useful alongside HbA1c; the two together read the trend properly. - Lipid Panel (Cholesterol, HDL, LDL, Triglycerides) — ↓ expected to fall
Triglycerides in particular fall with weight loss and improved insulin sensitivity.
What to do: Re-check at 12 weeks rather than chasing early numbers. - Lipase — ↑ expected to rise
Lipase and amylase can rise without pancreatitis on this class. An isolated mild elevation in someone with no symptoms is common.
What to do: Severe, persistent abdominal pain radiating to the back is the thing that matters, not the number. Symptoms decide, not a mild enzyme rise. - Comprehensive Metabolic Panel (CMP) — ◆ worth watching
Rapid weight loss and reduced intake shift electrolytes and kidney markers; dehydration from nausea or vomiting shows up here first.
What to do: Worth a baseline. If you have been vomiting, this is the panel that catches the consequence. - Ferritin — ↓ expected to fall
Not the drug — the eating. Sharply reduced intake drops iron, B12 and protein intake with it, and this is the most commonly missed consequence of a good response.
What to do: Check ferritin and B12 at 12 weeks. Muscle loss and hair shedding on a GLP-1 is very often a nutrition problem wearing a drug's name.
The pattern with this class is that the frightening-looking numbers (lipase) are usually fine and the boring ones (ferritin, B12) are where the real damage happens.
- How to work up to it, and when not to
- When to take it, and why that window
- Cycle length
- Time off between cycles
- Fasted or fed, and when in the day
- Needle gauge and injection site
- Coach Cam's personal notes
- Which compounds push the same lever, and why the dose adds up faster than people count
- What blunts it — the stacks that waste your money
- What compounds the risk, so a side effect arrives sooner than any one of them suggests
- Coach Cam's read on running it alongside the rest of your protocol
Everything above is free and stays free. Skool is where it becomes a plan — Amycretin in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside Amycretin
Baseline first, then again at 8–12 weeks.
| Marker | What it’s watching for |
|---|---|
| HbA1c (Hemoglobin A1c) | Where you started, so you can prove the change was real |
| Fasting Insulin | Moves years before HbA1c does — the earliest signal you get |
| Lipid Panel (Cholesterol, HDL, LDL, Triglycerides) | Rapid fat loss shifts triglycerides fast, in both directions |
| Comprehensive Metabolic Panel (CMP) | Liver, kidney and electrolytes while intake is restricted |
The Metabolic Health & Prediabetes panel covers these in one order — 8 markers, $81.45 with the discount applied.
Check results you already have → · All 103 markers A–Z
Amycretin — frequently asked questions
What is Amycretin?
Amycretin (Amylin / GLP-1 unimolecular) is a metabolic & fat loss research compound. Single molecule hitting both amylin and GLP-1 receptors — additive appetite suppression via different brain circuits; oral and injectable forms.
Is the full Amycretin protocol on this page?
The reported research dose is on this page, along with how Amycretin works and the evidence behind it. The protocol — how to work up to it, frequency, cycle length, time off, what not to stack it with and Coach Cam's notes — is inside Skool.
What is the half-life of Amycretin?
Amycretin has an approximate half-life of Form-dependent (oral vs subq), which is part of what determines how often it's dosed.
What's the evidence behind Amycretin?
Current evidence level: Phase 1/2 human (~10-13% in 12 wks). Amycretin is offered for research purposes only and is not an approved medicine.
What Amycretin is used for
Amycretin appears under 2 goals in the goal router.
Related Metabolic & Fat Loss compounds
Where this goes next
The pages here are the frameworks. The protocols — the dosing, the order to correct things in, the week-by-week schedule and what to retest — are inside Skool.