MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Amycretin Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Amycretin (zenagamtide, Novo Nordisk code NN9487) is an investigational, unimolecular GLP-1 and amylin receptor agonist for obesity and type 2 diabetes, built from covalently linked GLP-1 and amylin analogues and acylated for albumin binding [1]. It is unusual in being developed in both a once-weekly subcutaneous injection and a once-daily oral tablet (the oral form uses the SNAC permeation enhancer) [2]. The GLP-1 arm drives satiety, slows gastric emptying, and improves glucose-dependent insulin secretion, while the amylin arm independently suppresses appetite — an additive combination. In the phase 1b/2a trial, once-weekly subcutaneous doses titrated to 1.25, 5, 20, and 60 mg produced roughly 9.7% to 24.3% weight loss over 20–36 weeks with no plateau [1][3]. Amycretin advanced to phase 3 in 2025 but is not approved by the FDA or EMA; the dosing and reconstitution details here are educational only, not medical advice.
Reconstitute: Add 2 mL bacteriostatic water → 10 mg/mL concentration.
Typical dose: 1.25–20 mg once weekly SC (up to 60 mg studied)
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution refrigerated at 2–8 °C and used within ~4 weeks. Protect from light; do not freeze the reconstituted solution or expose it to heat.
Half-life: Long-acting (multi-day) via C18-diacid albumin binding — supports once-weekly subcutaneous and once-daily oral dosing; exact human terminal half-life not yet published [5][8].
Route: Investigational once-weekly subcutaneous injection and once-daily oral tablet (modeled here as a subcutaneous reconstitution protocol) [1][2].
Status: Investigational; not FDA- or EMA-approved. Advanced to phase 3 in 2025 (Novo Nordisk). Research/educational use only [3].
About Amycretin
Amycretin (zenagamtide, NN9487) is an investigational, unimolecular GLP-1 and amylin receptor agonist developed by Novo Nordisk for obesity and type 2 diabetes [1][2]. It is genuinely a subcutaneous drug: the pivotal phase 1b/2a study dosed it once weekly by subcutaneous injection, so the reconstitution model below reflects one of its real research routes. (A separate once-daily oral tablet, co-formulated with the SNAC absorption enhancer, is being developed in parallel [2].)\n\nThis guide models a 20 mg vial reconstituted with 2.0 mL of bacteriostatic water (10 mg/mL, or 100 mcg per insulin-syringe unit) so the studied Amycretin dosage steps map cleanly onto a U-100 syringe: 1.25 mg ≈ 12.5 units, 5 mg ≈ 50 units, and 20 mg ≈ 200 units (2.0 mL, drawn as two injections). The 60 mg dose explored at the top of the trial requires multiple vials and split injections. Trials escalated slowly to limit gastrointestinal side effects, holding each maintenance step for several weeks before the next increase [1][3].\n\nFrequency: Inject once weekly subcutaneously (abdomen, thigh, or upper arm), rotating sites [1]. Amycretin is not FDA- or EMA-approved and is presented here for educational purposes only.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 2.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner wall of the 20 mg Amycretin vial; do not spray it directly onto the powder, and do not shake.
Gently swirl or roll the vial until the solution is completely clear; this yields a 10 mg/mL concentration (100 mcg per insulin-syringe unit).
Store refrigerated at 2–8 °C and draw the prescribed units per weekly dose (1.25 mg ≈ 12.5 units, 5 mg ≈ 50 units, 20 mg ≈ 200 units split across two injections; 60 mg requires multiple vials).
Inject subcutaneously into a rotated site; do not aspirate, inject slowly, and wait a few seconds before withdrawing the needle to ensure the full dose is delivered.
Interactive Amycretin Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 2mL water yields 10.00 mg/mL. To evaluate a 250mcg dose, pull to 2.5 units (3 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Weeks 1–4 (Initiation) | 1250 mcg (1.25 mg) | 13 units (0.13 mL) |
| Weeks 5–12 (Escalation) | 5000 mcg (5 mg) | 50 units (0.50 mL) |
| Weeks 13–20 (Maintenance) | 20000 mcg (20 mg) | 200 units (2.00 mL) |
| Highest studied (≥Week 21) | 60000 mcg (60 mg) | 600 units (6.00 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 20 mg vial.
Peptide Vials (Amycretin, 20 mg each):
- check8 weeks (titrate 1.25 → 5 mg): ~3 vials
- check12 weeks (titrate to 20 mg): ~6 vials
- check16 weeks (20 mg maintenance): ~10 vials
Insulin Syringes (U-100):
- checkPer week: 1–3 syringes (20 mg and higher doses are split across 2–3 injections)
- check8 weeks: ~10–14 syringes
- check16 weeks: ~24–32 syringes
Bacteriostatic Water (30 mL bottles): Use 2 mL per vial for reconstitution.
- check8 weeks (3 vials): ~6 mL
- check12 weeks (6 vials): ~12 mL → 1 × 30 mL bottle
- check16 weeks (10 vials): ~20 mL → 1 × 30 mL bottle
Alcohol Swabs: One for the vial stopper plus one per injection site.
- checkPer week: 3–6 swabs
- check8 weeks: ~40 swabs
- check16 weeks: ~80–100 swabs → 1 × 100-count box
Mechanism of Action (MOA)
Amycretin is a single, unimolecular peptide engineered by Novo Nordisk (development code NN9487; proposed INN zenagamtide) in which analogues of glucagon-like peptide-1 (GLP-1) and the pancreatic hormone amylin are covalently linked into one molecule [1][8]. The construct is acylated with a C18 diacid fatty-acid side chain that promotes reversible binding to serum albumin — the same protraction strategy used for semaglutide — which slows clearance and extends the systemic half-life enough to support once-weekly subcutaneous dosing [5][8]. For the oral tablet, amycretin is co-formulated with the absorption enhancer SNAC (salcaprozate sodium) to permit gastric uptake, enabling once-daily oral administration [2].\n\nThe two receptor arms are pharmacologically complementary. The GLP-1 component acts on receptors in the hypothalamus and brainstem to reduce food intake, slows gastric emptying, and enhances glucose-dependent insulin secretion while suppressing glucagon — the canonical incretin effect. The amylin component signals through the amylin receptor (a calcitonin-receptor core complexed with receptor-activity-modifying proteins) to independently promote satiety, slow gastric emptying, and reduce food intake. Because amylin and GLP-1 curb appetite through partially distinct central pathways, combining them in one molecule produces additive — and potentially synergistic — effects on energy intake and body weight, the same rationale behind Novo Nordisk's CagriSema (cagrilintide plus semaglutide), now delivered from a single molecule [1].\n\nPharmacokinetics: amycretin is delivered subcutaneously into the abdomen, thigh, or upper arm (once weekly) or orally (once daily). The acylated, albumin-binding design yields a long, multi-day effective half-life that justifies weekly subcutaneous dosing; exact human terminal half-life values from the phase 1 program are not yet fully published, but preclinical intravenous half-lives rose with species size (about 5.9 hours in rats, 29 hours in non-human primates, and 54 hours in minipigs), consistent with a protracted human profile [5]. Plasma exposure was broadly dose-proportional across the studied range, and a slow stepwise titration is used because tolerance to the gastrointestinal effects develops gradually [1].\n\nDownstream, the dual mechanism drives substantial, dose-dependent weight loss without a plateau at the end of the dosing periods studied: once-weekly subcutaneous maintenance doses of 1.25, 5, 20, and 60 mg produced roughly 9.7%, 16.2%, 22.0%, and 24.3% body-weight reductions over 20–36 weeks [1][3]. In type 2 diabetes, the same dual signalling lowered HbA1c by up to 1.8% alongside weight loss [4]. The real-world research routes here are once-weekly subcutaneous injection and once-daily oral tablet; the subcutaneous reconstitution figures on this page model the injectable route used in the pivotal phase 1b/2a study. Amycretin remains investigational and is not approved by any regulator [3].
Clinical Trial Efficacy Highlights
- starIn the phase 1b/2a subcutaneous trial (The Lancet, 2025; 125 adults with overweight or obesity, BMI 27.0–39.9), once-weekly amycretin titrated to maintenance doses of 1.25 mg, 5 mg, and 20 mg produced estimated body-weight reductions of 9.7% at 20 weeks, 16.2% at 28 weeks, and 22.0% at 36 weeks, versus a 1–2% gain on placebo, assuming full adherence [1][3].
- starThe highest subcutaneous dose, 60 mg once weekly, reduced body weight by approximately 24.3% at 36 weeks versus 1.1% with placebo, with no weight-loss plateau observed at the end of the treatment period — a trajectory suggesting further loss might occur with longer dosing [1][3].
- starIn the first-in-human phase 1 trial of the oral tablet (The Lancet, 2025; 144 adults without diabetes, BMI 25.0–39.9), once-daily oral amycretin escalated to 100 mg/day produced a mean weight loss of 13.1% versus 1.2% with placebo over just 12 weeks, supporting development of the oral formulation in parallel with the injectable [2][3].
- starA phase 2 trial in 448 adults with type 2 diabetes inadequately controlled on metformin (with or without an SGLT2 inhibitor) reported, at 36 weeks, subcutaneous amycretin HbA1c reductions of up to 1.8% with up to 89.1% of participants reaching HbA1c below 7%, plus weight loss of up to 14.5% versus 2.6% on placebo [4].
- starIn the same phase 2 diabetes trial, the oral formulation lowered HbA1c by up to 1.5% (77.6% reaching <7%) and reduced body weight by up to 10.1% versus 2.5% with placebo, confirming clinically meaningful activity by both routes [4].
- starPreclinical work in mice and rats (eBioMedicine, 2025) demonstrated that amycretin engages both GLP-1 and amylin receptors and produces greater weight loss and metabolic improvement than single-pathway agonists, establishing the dual-agonist rationale that carried into the clinic [5].
- starCross-trial tolerability analyses presented at ADA 2025 found that both oral and subcutaneous amycretin had safety and gastrointestinal-tolerability profiles broadly consistent with established GLP-1 monoagonists, despite the added amylin activity [6][7].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningGastrointestinal events dominated the safety profile: in the subcutaneous phase 1b/2a trial, nausea was reported in up to ~82%, vomiting in ~53%, and diarrhea in ~41% of treated participants, most often during dose escalation and generally mild to moderate and transient [1][6].
- warningA serious adverse event of gallstone (biliary) pancreatitis occurred in a participant on the 20 mg subcutaneous dose; it recurred but ultimately resolved — gallbladder and pancreatitis events are a recognized class concern with incretin therapies [1].
- warningDecreased appetite is part of the intended mechanism but can lead to reduced food and fluid intake with a risk of dehydration; slow titration and adequate hydration are used to mitigate this [3].
- warningModest resting heart-rate increases are expected with GLP-1/amylin agonists; longer and larger trials are needed to characterize cardiovascular effects, which were not the primary endpoint of these early-phase studies [1].
- warningAs with semaglutide- and tirzepatide-class agents, a portion of the weight lost is lean body mass; adequate dietary protein and resistance training are commonly recommended during active weight loss, though amycretin-specific body-composition data remain limited [1].
- warningBy GLP-1 class labeling, agents in this family carry warnings around a personal or family history of medullary thyroid carcinoma or MEN2, pancreatitis, and use in pregnancy; amycretin has not completed the safety evaluation needed to define its own contraindications [3].
- warningAmycretin should not be combined with other GLP-1, amylin, GIP, or incretin agents (e.g., semaglutide, tirzepatide, cagrilintide); overlapping mechanisms would compound gastrointestinal toxicity and hypoglycemia risk (especially with insulin or sulfonylureas) without proven benefit.
- warningRegulatory/research status: amycretin is NOT approved by the FDA, EMA, or any regulator; it advanced to phase 3 in 2025 and is available only as an investigational/research compound. Long-term human safety is not established [3].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Amycretin dosage?expand_more
In clinical research, amycretin is given as a once-weekly subcutaneous injection titrated slowly upward — the phase 1b/2a study used maintenance doses of 1.25 mg, 5 mg, 20 mg, and (at the top of the range) 60 mg per week, with each step held for several weeks to limit nausea [1][3]. A once-daily oral tablet has been studied from 1 mg up to 100 mg/day [2]. There is no approved or established human dose; these are investigational research figures, not a prescription. Any dosing decision belongs with a qualified clinician within a monitored trial.
Is Amycretin FDA approved?expand_more
No. Amycretin is not approved by the FDA, the EMA, or any other regulator for any indication. Based on its phase 1 and phase 1b/2a results published in The Lancet in 2025, Novo Nordisk advanced both the oral and subcutaneous forms into phase 3 development, but it remains investigational and is sold only as a research compound. Nothing on this page is medical advice [3].
How do you reconstitute Amycretin for subcutaneous dosing?expand_more
In this educational model, a 20 mg vial is reconstituted with 2.0 mL of bacteriostatic water, giving 10 mg/mL (100 mcg per unit on a U-100 syringe). Add the water slowly down the vial wall, swirl gently until clear (do not shake), and refrigerate at 2–8 °C. At that concentration, 1.25 mg is about 12.5 units, 5 mg is 50 units, and 20 mg is 200 units (drawn as two 1 mL injections); the 60 mg dose requires multiple vials and split injections.
What is the half-life of Amycretin?expand_more
Amycretin is acylated with a C18 diacid fatty-acid chain that binds reversibly to albumin, giving a long, multi-day effective half-life — enough to support once-weekly subcutaneous dosing and, in the oral tablet, once-daily dosing [5][8]. Exact human terminal half-life values from the phase 1 program have not been fully published; preclinical intravenous half-lives ranged from about 5.9 hours in rats to 54 hours in minipigs, consistent with a protracted human profile [5].
Can Amycretin be stacked with semaglutide or tirzepatide?expand_more
No. Amycretin already combines GLP-1 and amylin receptor agonism in one molecule, so layering it onto semaglutide, tirzepatide, cagrilintide, or any other GLP-1/GIP/amylin agent would stack overlapping mechanisms and sharply raise the risk of severe gastrointestinal effects and hypoglycemia (especially alongside insulin or sulfonylureas) without evidence of added benefit. Clinicians transition between such agents rather than combining them.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Amycretin, plus the universal dosing calculator.
Academic References & Study Citations
Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. Lancet. 2025 (published online June 20, 2025). View Scientific Paper →
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. Lancet. 2025. DOI 10.1016/S0140-6736(25)01176-6. View Scientific Paper →
Novo Nordisk. Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase results published in The Lancet (subcutaneous up to 24.3% and oral 13.1% weight loss). June 20, 2025. View Scientific Paper →
Novo Nordisk. Phase 2 trial with amycretin reports significant weight loss and HbA1c reduction in type 2 diabetes. November 25, 2025. View Scientific Paper →
The effect of amycretin, a unimolecular GLP-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats. eBioMedicine. 2025. View Scientific Paper →
Subcutaneous Amycretin Yields Promising Weight Loss in Phase 1b/2a Trial. HCPLive. 2025. View Scientific Paper →
Oral, Subcutaneous Amycretin Similarly Safe, Tolerated as GLP-1 Monoagonists. American College of Cardiology, Journal Scan. July 2, 2025. View Scientific Paper →
Amycretin (zenagamtide, development code NN9487) — drug overview, structure, and clinical status. Wikipedia. View Scientific Paper →