Amycretin: research
An experimental fullness-hormone drug studied as daily tablets and weekly injections.
Also called: Zenagamtide, NNC0487-0111, NN9487, NN 9487.
Amylin / GLP-1 co-agonists · Unimolecular GLP-1 and amylin receptor agonist; also activates calcitonin receptors.
31 registered trials: 9 completed, 22 ongoing or planned. Five human papers cover four trials and 759 participants; phase 3 has no reported results.
Studies
- First oral trial. rct, n=144, Adults 18–55 without diabetes; BMI 25.0–34.9 in A/B and 27.0–39.9 in C/D.. Oral tablets reduced weight over 12 weeks; weight was an exploratory outcome. (source)
- First injection trial. rct, n=125, Adults 18–55, BMI 27.0–39.9, without diabetes.. Weekly injections reduced weight, but small arms and many withdrawals limit certainty. (source)
- Diabetes: daily tablets. rct, n=186, Adults 18–75 with type 2 diabetes; HbA1c 7.0–10.0%, BMI 23.0 to <50.0; metformin with or without an SGLT2 inhibitor.. All three oral doses lowered HbA1c; 25 and 50 mg also reduced weight versus placebo. (source)
- Diabetes: weekly injections. rct, n=262, Adults 18–75 with type 2 diabetes; HbA1c 7.0–10.0%, BMI 23.0 to <50.0; metformin with or without an SGLT2 inhibitor.. Weekly injections lowered HbA1c and weight; higher doses caused more discontinuations. (source)
- Kidney function: one dose. pk-study, n=42, Adults 18–80; normal kidney function or mild, moderate, severe impairment, or dialysis.. Kidney impairment caused no clinically important exposure change after one 0.3 mg dose. (source)
- Japanese men: oral PK. rct, n=36, Japanese men with obesity.. Completed; efficacy and safety results are not available. (source)
- Birth control and stomach emptying. open-label, n=43, Women unable to become pregnant.. Completed; efficacy and safety results are not available. (source)
- Tablet formulation and food. rct, n=133, Adults with overweight or obesity.. Completed; efficacy and safety results are not available. (source)
- Chinese adults: oral PK. rct, n=29, Chinese adults with BMI ≥24.. Completed; efficacy and safety results are not available. (source)
- Chinese adults: injection PK. rct, n=36, Chinese adults with BMI 24.0–34.9.. Completed; efficacy and safety results are not available. (source)
- AMAZE 1: obesity. rct, n=1150, Adults with overweight or obesity.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 8: versus semaglutide. rct, n=1000, Adults with excess weight and type 2 diabetes.. Not yet recruiting; efficacy and safety results are not available. (source)
- AMAZE 5: knee pain. rct, n=400, Adults with excess weight and knee osteoarthritis.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 12: weight maintenance. rct, n=606, Adults with excess weight after a zenagamtide lead-in.. Active not recruiting; efficacy and safety results are not available. (source)
- Appetite and food intake. rct, n=120, Adults with obesity.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 6: knee pain. rct, n=400, Adults with excess weight and knee osteoarthritis.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 2: obesity with diabetes. rct, n=630, Adults with excess weight and type 2 diabetes.. Recruiting; efficacy and safety results are not available. (source)
- Insulin action study. rct, n=80, Adults with type 2 diabetes.. Recruiting; efficacy and safety results are not available. (source)
- HF-POLARIS: heart failure. rct, n=5610, Adults with excess weight and preserved or mildly reduced heart pumping function.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 3: sleep apnea, no PAP. rct, n=300, Adults with excess weight and sleep apnea without positive airway pressure.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 4: sleep apnea with PAP. rct, n=300, Adults with excess weight and sleep apnea using positive airway pressure.. Recruiting; efficacy and safety results are not available. (source)
- Liver function: single-dose PK. pk-study, n=35, Adults with normal liver function or mild, moderate or severe impairment.. Not yet recruiting; efficacy and safety results are not available. (source)
- AMAZE 13: Asian participants. rct, n=400, Asian adults with overweight or obesity.. Not yet recruiting; efficacy and safety results are not available. (source)
- AMAZE 7: versus semaglutide. rct, n=650, Adults with obesity.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 9: tablets for obesity. rct, n=950, Adults with obesity.. Recruiting; efficacy and safety results are not available. (source)
- Energy use after weight loss. rct, n=120, Adults with overweight or obesity.. Recruiting; efficacy and safety results are not available. (source)
- AMBITION 7: versus insulin. rct, n=1778, Adults with type 2 diabetes, high heart risk and 1–3 oral diabetes medicines.. Recruiting; efficacy and safety results are not available. (source)
- Meals, water and absorption. rct, n=320, Adults with overweight or obesity.. Recruiting; efficacy and safety results are not available. (source)
- AMAZE 10: Japan. rct, n=400, Adults in Japan with excess weight.. Recruiting; efficacy and safety results are not available. (source)
- Switch from semaglutide. open-label, n=60, Adults with excess weight, with or without type 2 diabetes.. Recruiting; efficacy and safety results are not available. (source)
- AMBIENCE: heart outcomes. rct, n=8500, Adults with excess weight and established artery disease.. Not yet recruiting; efficacy and safety results are not available. (source)
- Switch from tirzepatide. open-label, n=60, Adults with excess weight, with or without type 2 diabetes.. Recruiting; efficacy and safety results are not available. (source)
- Amylin drugs: indirect comparison. meta-analysis, n=4642, Six trials in adults with overweight or obesity without diabetes.. Amycretin ranked highly, but sparse and low-certainty indirect evidence limits comparison. (source)
- Weight-loss medicines: updated review. systematic-review, n=25816, 38 trials, 25,816 adults without diabetes; trials lasted at least 16 weeks.. The review supports early weight loss but could not pool the varied trial designs. (source)
- Receptors, appetite and liver fat. animal, Cell systems, obese mice and rats; additional animal pharmacokinetic experiments.. Animal experiments show appetite effects and receptor activity; they do not set human doses. (source)
Amycretin dosage
Typical reported dose: Weekly shot: 0.3 mg to start, raised up to 20 mg
- Oral safety study: 1 mg: 1 mg once one dose only, by mouth. Studied in a trial. Studied in: Adults 18–55, BMI 25.0–34.9, without diabetes. (source)
- Oral safety study: 3 mg: 3 mg once one dose only, by mouth. Studied in a trial. Studied in: Adults 18–55, BMI 25.0–34.9, without diabetes. (source)
- Oral safety study: 6 mg: 6 mg once one dose only, by mouth. Studied in a trial. Studied in: Adults 18–55, BMI 25.0–34.9, without diabetes. (source)
- Oral safety study: 12 mg: 12 mg once one dose only, by mouth. Studied in a trial. Studied in: Adults 18–55, BMI 25.0–34.9, without diabetes. (source)
- Oral safety study: 18 mg: 12 mg + 6 mg together once one dose only, by mouth. Studied in a trial. Studied in: Adults 18–55, BMI 25.0–34.9, without diabetes. (source)
- Oral safety study: 25 mg: 25 mg once one dose only, by mouth. Studied in a trial. Studied in: Adults 18–55, BMI 25.0–34.9, without diabetes. (source)
These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.
Amycretin side effects and risks
Reported side effects
- Nausea: Diabetes injections: 11–50% by dose versus 14% placebo. Tablets: 11–35% versus 3%., moderate. Discuss persistent symptoms before any increase; large meals may worsen them. (source)
- Vomiting: Diabetes injections: 3–29% versus 6% placebo. Tablets: 7–16% versus 0%., moderate. Repeated vomiting or inability to keep fluids down needs prompt assessment. (source)
- Diarrhea: Diabetes injections: 5–37% versus 6% placebo. Tablets: 6–8% versus 7%., moderate. Watch fluid intake and urine output; seek care for dehydration. (source)
- Constipation: Early 20 mg injection arm: 44% versus 20% placebo. Diabetes injections: 3–11% versus 3%., moderate. Report persistent constipation. Severe pain, swelling or inability to pass gas needs urgent care. (source)
- Altered or sensitive skin: Diabetes injections: 21% at 40 mg versus 0% placebo; 8% at 10 mg and 5% at 20 mg., moderate. Report burning, tingling or painful skin; rule out other causes. (source)
- Reflux, indigestion and burping: Oral diabetes trial: reflux 4–10% versus 3% placebo; burping 0–6% versus 0%., mild (source)
- Fatigue or weakness: Oral diabetes trial: fatigue 2–8% versus 3% placebo; weakness 2–6% versus 0%., moderate (source)
- Faster heart rate: Week 36 diabetes injections: mean rise 1.96–8.65 beats/min across doses versus −1.40 with placebo., moderate. Report sustained racing heart, palpitations or faintness. (source)
- Acute pancreatitis: Early trial: 1 mild, non serious gallstone case in 20 mg arm; last dose 2.5 mg. Oral diabetes: 1/54 (2%) at 6 mg; other oral arms/placebo 0. Injected diabetes: 0., serious. Severe lasting upper belly pain needs urgent care; normal enzyme tests did not exclude the reported case. (source)
- Severe low blood sugar: Injected diabetes trial: 1/38 (3%) at 20 mg; all other doses and placebo 0., serious. Risk may rise with insulin or sulfonylureas; confusion or unresolved symptoms need emergency care. (source)
- Kidney injury from fluid loss: One acute kidney injury caused withdrawal at oral 50 mg: 1/51 (2%)., serious. Get care for repeated vomiting, very little urine or marked dizziness. (source)
- Gallstone disease: Injected diabetes trial: 1/36 at 1.5 mg, 1/37 at 5 mg and 1/36 placebo, each reported as 3%., serious. Right upper belly pain with fever or yellow skin needs urgent assessment. (source)
Stop and get help if
- Severe lasting upper belly pain, especially into the back, with or without vomiting: Stop exposure and get urgent medical care for possible pancreatitis.
- Swollen tongue or throat, trouble breathing, widespread hives or collapse: Call emergency services now; possible severe allergic reaction.
- Repeated vomiting, inability to drink, very little urine or marked dizziness: Get urgent assessment for dehydration or kidney injury.
- Chest pain, fainting or sustained racing heart: Call emergency services for chest pain or fainting; seek urgent care for a sustained racing heart.
- Sudden vision loss or major new vision changes: Get urgent eye assessment.
- Confusion, seizure, unconsciousness or low-glucose symptoms that do not resolve: Call emergency services. Do not give food or drink to someone who cannot swallow safely.
- Severe swollen belly, vomiting and inability to pass stool or gas: Get urgent care for possible bowel obstruction.
- Right upper belly pain with fever or yellow skin: Get urgent assessment for gallbladder or bile-duct disease.
Who should avoid it
- pregnant: Pregnant people were excluded. Fetal safety is unknown; this is an investigational appetite-suppressing drug.
- breastfeeding: Breastfeeding people were excluded. Effects on milk and infants are unknown.
- tryingToConceive: People planning pregnancy were excluded. No amycretin-specific preconception washout has been established.
- under18: Human trials enrolled adults. Safety and dosing below 18 are not established.
- mtcOrMen2: Personal or family medullary thyroid cancer or MEN2 excluded in trials; GLP-1 class precaution, not an amycretin label.
- eatingDisorderHistory: Appetite suppression may worsen unsafe restriction. Early trials excluded eating disorders; no recovery protocol is established.
- pancreatitisHistory: Trials excluded prior pancreatitis. One confirmed case occurred in the oral diabetes trial.
- gastroparesis: Severe slow stomach emptying was excluded. GLP-1 class effects may worsen symptoms.
- diabeticRetinopathy: Unstable diabetic eye disease was excluded. Rapid blood sugar improvement warrants an eye-care review.
- kidneyDisease: One low-dose kidney study was reassuring. Dehydration and long-term high-dose safety still need attention.
- liverDisease: People with substantial liver test abnormalities were excluded; a liver-impairment PK trial has no results.
- gallbladderDisease: Gallstone events occurred in the diabetes trial. Weight loss and GLP-1 class effects warrant review of prior gallbladder disease.
- heartCondition: Heart rate increased in trials; recent heart attack, stroke or unstable heart disease were excluded.
- uncontrolledBloodPressure: Uncontrolled blood pressure was excluded in early trials. Review blood pressure and heart symptoms before exposure.
- surgeryPlanned: GLP-1 class delay in stomach emptying can affect anesthesia safety. Tell the procedure team; no amycretin-specific hold schedule exists.
- diabetes: Monitor glucose closely, especially with other glucose-lowering medicines. A severe low-glucose event occurred at 20 mg.
- cancerHistory: Recent cancers were excluded from early trials. Long-term cancer safety is unknown; this does not show that amycretin causes cancer.
- other: Known or suspected serious allergy to the study drug or related products was an exclusion.
- other: Calcium/PTH disorders and prior bisphosphonate or denosumab use were excluded. Calcitonin receptor activity warrants review.
- testedAthlete: Its unapproved status brings it under WADA S0, prohibited in and out of competition.
Interactions
- Insulin: GLP-1/amylin effects plus insulin may cause low blood sugar. A combination dose-adjustment protocol for amycretin is not established.
- Sulfonylureas: Additive blood sugar lowering may cause hypoglycemia; amycretin trials did not establish this combination.
- Other GLP-1 or amylin drugs: Overlapping appetite and stomach effects; no established combination protocol. Registered switch studies test sequential use, not stacking.
- Oral medicines with narrow dosing margins: Class-based concern: stomach emptying changes may alter absorption. Drug-level or INR checks may be needed; amycretin-specific effects are unknown.
- Oral birth control: A completed amycretin birth-control interaction study has no public results. Absorption effects and any extra contraception interval are unknown.
- Bisphosphonates and denosumab: The phase 2 trial excluded prior use and calcium disorders. A calcium-related interaction is a precaution, not a measured amycretin effect.
- Metformin and SGLT2 inhibitors: These were background medicines in phase 2. That trial experience does not establish safety for every patient or other drug combinations.
Product quality risks
- No published independent assay of retail amycretin products was located. Online availability does not confirm identity, dose or sterility.
- Adjacent evidence only: three tested online semaglutide samples had 7–14% purity and 29–39% more drug than labeled.
- One semaglutide sample had endotoxin at 8.95 EU/mg despite no viable microbes. These findings cannot be assigned an amycretin contamination rate.
- Amycretin has no approved retail pen; any claimed approved amycretin pen or tablet warrants verification.
- FDA warns of unapproved GLP-1 product quality and dose errors. Its named compounding warning concerns other drugs, not an amycretin-specific ruling.
How Amycretin works
It copies two hormone signals that help control hunger and blood sugar. GLP-1 helps release insulin when blood sugar rises. Amylin adds a fullness signal. Cell tests also show calcitonin receptor activity; its separate effects in people are unclear.
- GLP-1 receptor: Helps signal fullness and release insulin when blood sugar is high.
- Amylin receptors: Adds signals that reduce eating and help people feel full.
- Calcitonin receptor: Activated in cell tests; its contribution to human benefits and harms is not established.
Half-life: About 3.3–4.1 days after injections in the first trial; 88.1 hours in people with normal kidney function in the kidney study.
Gaps: No phase 3 results, cardiovascular benefit, long-term rare-harm rates or approved dose label. Five human papers represent four trials and 759 people. The 31-trial count includes planned studies and counts the oral/injected phase 2 trial once. No published outcomes located for five completed registry trials: Japanese oral PK, food/formulations, contraceptive interaction and two Chinese PK trials. No reliable nontrial self-use dose, microdose, cycling schedule or weight-loss stack was located. No home-vial size, diluent, water volume or validated storage-after-mixing period could be established. No study of online amycretin purity, potency, endotoxin or sterility was located. Semaglutide findings are adjacent evidence. Pregnancy, breastfeeding, adolescents and long-term cancer safety remain unstudied. No validated amycretin-specific surgery hold, pregnancy washout or oral-contraception backup interval. Registry with Chinese oral dosing conflicts internally: title says 10 days; arms say single doses. Do not infer a schedule. The 60 mg injection obesity arm held 60 mg for only 4 weeks. It is not a proven long-term maintenance dose. No reliable legal determination of Australian scheduling or country-specific personal import and possession rules was established. No established clinician-published amycretin prescribing protocol was located; online dose calculators are not clinical practice evidence.
Sources
- 21 CFR 216.23 — Bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act., Office of the Federal Register · eCFR · 2026
- 503B Bulk Drug Substances List, FDA · FDA · 2026
- Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act, FDA · FDA · 2026
- Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act, FDA · FDA · 2026
- FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss, FDA · FDA · 2026
- The 2026 Prohibited List, World Anti-Doping Agency · WADA · 2026
- Therapeutic Goods (Poisons Standard—October 2026) Instrument 2026, Australian Government · Australian Government · 2026
- Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act, FDA · FDA · 2025
- Wegovy PI, Novo Nordisk
- Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review., Moiz A et al. · Annals of internal medicine · 2026
- Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial., Mora P et al. · Lancet (London, England) · 2026
- Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial., Mora P et al. · Lancet (London, England) · 2026
- Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis., Kamrul-Hasan ABM et al. · Endocrinology, diabetes & metabolism · 2026
- Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide., Oldenburg LIK et al. · Diabetes, obesity & metabolism · 2026
- Supplementary appendix, Mora P et al. · The Lancet · 2026
Sources checked: 2026-10-18.
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