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.
AOD-9604 Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
AOD-9604 is a synthetic 16-amino-acid peptide corresponding to the C-terminal lipolytic domain of human growth hormone (residues 176–191), engineered to retain hGH's fat-mobilization activity while removing the receptor-binding region responsible for IGF-1 release, anabolic muscle growth and glucose intolerance. The peptide activates beta-3 adrenergic receptor signaling in adipocytes, increasing hormone-sensitive lipase activity and triglyceride hydrolysis without engaging the GH receptor itself [1]. Six Phase 1 and Phase 2 trials enrolling roughly 900 participants demonstrated a clean safety profile, but the 12-week placebo-controlled obesity trial in obese adults showed only 2.6 kg of weight loss on 1 mg/day vs 0.8 kg on placebo — modest enough that Metabolic Pharmaceuticals halted obesity development in 2007 [2]. AOD-9604 holds FDA GRAS status as a food ingredient but is not approved as a drug.
Reconstitute: Add 3 mL bacteriostatic water → 0.667 mg/mL concentration.
Easy measuring: At 0.667 mg/mL, 1 unit = 0.01 mL = 0.0067 mg (7 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen; reconstituted refrigerated; avoid repeated freeze–thaw.
Half-life: Very short — approximately 15–30 minutes after subcutaneous administration. Despite rapid clearance, lipolytic effect persists several hours via downstream cAMP signaling in adipocytes.
Regulatory status: Not FDA approved as a drug. Holds FDA GRAS (Generally Recognized as Safe) status (GRN 525, 2014) for use as a food ingredient. Sold by research-chemical suppliers strictly for laboratory use.
Efficacy ceiling: Placebo-subtracted weight loss of just 1.8 kg over 12 weeks (and 2.0 kg at 23 weeks) — roughly one tenth of what semaglutide achieves at 68 weeks. Clean mechanism but modest absolute effect [2].
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 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid foaming.
Gently swirl/roll until dissolved (do not shake).
Inject slowly; wait a few seconds before withdrawing the needle.
Do not aspirate for subcutaneous injections; inject slowly and steadily[13].
Interactive AOD-9604 Syringe Calculator
Currently visualizing the 2 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 2mg dry powder in 3mL water yields 0.67 mg/mL. To evaluate a 250mcg dose, pull to 37.5 units (38 syringe ticks).
U-100 Syringe Representation
37.5 Units (38 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–4 | 300 mcg | 45 units (0.45 mL) |
| Weeks 5–12 | 500 mcg | 75 units (0.75 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 2 mg vial.
Peptide Vials (AOD-9604, 2 mg each):
- check8 weeks ≈ 12 vials
- check12 weeks ≈ 19 vials
- check16 weeks ≈ 26 vials
Insulin Syringes (U‑100):
- checkPer week: 7 syringes (1/day)
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
- check16 weeks: 112 syringes
Bacteriostatic Water (10 mL bottles): Use 3.0 mL per vial for reconstitution.
- check8 weeks (12 vials): 36 mL → 4 × 10 mL bottles
- check12 weeks (19 vials): 57 mL → 6 × 10 mL bottles
- check16 weeks (26 vials): 78 mL → 8 × 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs → recommend 2 × 100‑count boxes
- check12 weeks: 168 swabs → recommend 2 × 100‑count boxes
- check16 weeks: 224 swabs → recommend 3 × 100‑count boxes
Mechanism of Action (MOA)
AOD-9604 (also called hGH 176–191) reproduces the C-terminal sequence of human growth hormone that mechanistic studies localized as the lipolytic active site. Heffernan et al. (Endocrinology 2001) demonstrated that the 176–191 fragment activates beta-3 adrenergic receptor signaling in adipocytes, producing dose-dependent increases in hormone-sensitive lipase activity and triglyceride hydrolysis comparable to full-length growth hormone — but without engaging the GH receptor or IGF-1 axis [1]. This mechanism distinguishes AOD-9604 from full-length hGH: it stimulates lipolysis without increasing IGF-1, without affecting glucose homeostasis or insulin sensitivity, and without producing the anabolic muscle-growth or organomegaly effects of complete growth hormone. The peptide also appears to weakly inhibit lipogenesis in vitro, providing a dual effect on fat balance. The pharmacokinetic profile is unusual. AOD-9604 has a very short plasma half-life of approximately 15–30 minutes after subcutaneous administration, with peak concentrations 15–30 minutes post-injection. Bioavailability is moderate (estimated 40–60%) and the molecule is rapidly cleared by proteolysis. Despite the short half-life, the lipolytic effect persists for several hours due to downstream cAMP-mediated signaling in adipocytes. Most research protocols use daily subcutaneous injection in the morning on an empty stomach, with doses commonly 250–500 mcg per administration — a regimen that produced the modest weight-loss signal in the Phase 2 trials. Downstream metabolic effects are limited relative to modern incretin therapies. The pivotal 12-week double-blind randomized trial conducted by Metabolic Pharmaceuticals in approximately 300 obese adults (Calvar et al.) showed placebo-subtracted weight loss of 1.8 kg on 1 mg/day with no significant effects on glucose, insulin, IGF-1 or cardiovascular markers [2]. A subsequent 23-week trial reproduced this modest effect (approximately 2.8 kg vs 0.8 kg placebo). Preclinical work in obese rodents had been more impressive — substantial reductions in body fat percentage — but the effect did not translate to human obesity at clinically meaningful magnitudes. The mechanism remains pharmacologically valid: AOD-9604 demonstrably activates beta-3 adrenergic lipolysis without endocrine disruption, but the absolute magnitude of fat mobilization in humans is too small to compete with incretin-class drugs. AOD-9604 has subsequently been investigated as a potential adjunct for osteoarthritis, cartilage repair and wound healing, where local injection of the peptide produces beneficial effects independent of weight loss.
Clinical Trial Efficacy Highlights
- starThe pivotal Phase 2 12-week trial in approximately 300 obese adults (Metabolic Pharmaceuticals, reported in company filings) compared AOD-9604 0.25, 0.5, 1.0 mg/day SC vs placebo. The 1 mg/day arm achieved 2.6 kg mean weight loss vs 0.8 kg on placebo — placebo-subtracted effect of 1.8 kg over 12 weeks [2].
- starA subsequent 23-week extension/repeat trial showed mean weight loss of approximately 2.8 kg vs 0.8 kg with placebo, demonstrating that the modest effect persists with longer treatment but does not accelerate over time — leading the manufacturer to halt obesity development [2].
- starAcross six Phase 1 and Phase 2 trials, no significant effects on fasting glucose, insulin sensitivity, IGF-1, or HbA1c were observed — confirming the design goal of separating lipolytic from anabolic/diabetogenic effects of full-length hGH [1][2].
- starHeffernan et al. (Endocrinology 2001) demonstrated dose-dependent lipolytic activity in isolated adipocytes from lean and obese mice and humans, with maximal effect comparable to full-length hGH at equimolar concentrations — establishing the molecular validity of the lipolytic domain hypothesis [1].
- starAOD-9604 received FDA GRAS (Generally Recognized as Safe) status in 2014 for use as a food ingredient, based on cumulative safety data from clinical trials — though this is not equivalent to drug approval and does not validate the lipolytic efficacy claims.
- starBody-composition substudies using DXA in the Phase 2 program showed approximately 70% of weight lost was fat mass, with no significant change in lean mass — a favorable composition ratio but small absolute magnitude [2].
- starInvestigator-led work on AOD-9604 for osteoarthritis and cartilage repair (Kwon et al., 2019) showed local intra-articular injection produced beneficial effects on cartilage matrix turnover in animal models — suggesting potential repositioning beyond obesity.
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.
- warningThe safety profile across six Phase 1 and Phase 2 trials enrolling roughly 900 participants was unremarkable, with adverse-event rates comparable to placebo. No genotoxicity, cardiotoxicity, or organ-specific toxicity was identified at doses up to 30 mg/day SC [2].
- warningMild injection-site reactions (erythema, transient discomfort) were reported in approximately 5–10% of participants, comparable to other subcutaneous peptides and resolving with site rotation.
- warningNo significant effects on glucose tolerance, fasting insulin or HbA1c were observed across all completed clinical trials — confirming the design goal of avoiding the diabetogenic risk of full-length growth hormone therapy [1][2].
- warningNo measurable changes in IGF-1, IGFBP-3 or growth-hormone-axis biomarkers were observed, supporting the mechanistic claim that AOD-9604 does not engage the GH receptor and is unlikely to produce anabolic or oncogenic effects.
- warningCardiovascular effects were minimal: no changes in heart rate, blood pressure, ECG parameters or lipid markers beyond those expected from minor weight reduction [2].
- warningHeadache, mild dizziness and transient mild fatigue were reported in <5% of participants, generally comparable to placebo rates and not clearly drug-attributable.
- warningLong-term safety data beyond 23 weeks is limited; theoretical concerns about prolonged beta-3 adrenergic stimulation in adipose tissue have not been systematically addressed in published trials.
- warningImportantly, the absence of efficacy beyond modest weight loss means risk/benefit even with a clean safety profile compares unfavorably to incretin-class drugs — a key reason for the halt of obesity development.
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 AOD-9604 dosage?expand_more
Research protocols typically use 250–500 mcg per dose, administered once daily subcutaneously, often in the morning on an empty stomach. The Phase 2 obesity trial used 1 mg/day. Cycles are typically 8–12 weeks at a time. No therapeutic medical use exists; these are research-chemical dosing patterns derived from the clinical trial literature.
How is AOD-9604 different from full-length growth hormone?expand_more
AOD-9604 is the C-terminal 176–191 fragment of hGH, retaining the lipolytic mechanism (beta-3 adrenergic activation) while removing the receptor-binding region that drives anabolic growth and IGF-1 release. Result: fat mobilization without muscle growth, organomegaly, glucose intolerance or oncogenic IGF-1 elevation — but also with substantially smaller weight-loss effect (~2.6 kg at 12 weeks) [1].
What are the most common side effects of AOD-9604?expand_more
Side-effect profile across ~900 trial participants was essentially placebo-equivalent. Most common: mild injection-site reactions (5–10%), occasional headache or mild dizziness. No significant effects on glucose, IGF-1, blood pressure, lipids or ECG. Long-term safety beyond 23 weeks is not characterized in published literature [2].
How should AOD-9604 be reconstituted and stored?expand_more
Lyophilized AOD-9604 is reconstituted with bacteriostatic water at 1–2 mL per 5 mg vial. Once mixed, store refrigerated at 2–8 C and use within 28 days. Unopened lyophilized vials remain stable for 18–24 months refrigerated; protect from light and heat. Do not freeze the reconstituted solution; discard if cloudy or discolored.
Is AOD-9604 FDA approved?expand_more
No, not as a drug. AOD-9604 holds FDA GRAS (Generally Recognized as Safe) status for use as a food/cosmetic ingredient, based on the clinical-trial safety database. It is not approved for obesity or any medical indication. It is sold by research-chemical suppliers strictly for laboratory use and is not legally available for human therapeutic use.
Academic References & Study Citations
Heffernan M, Summers RJ, Thorburn A, et al. (2001) Endocrinology 142:5182-5189. 'The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta3-AR knock-out mice'. View Scientific Paper →
Ng FM, Sun J, Sharma L, et al. (2000) Horm Res 53:274-278. 'Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone'. View Scientific Paper →
Heffernan MA, Jiang WJ, Thorburn AW, Ng FM. (2000) Am J Physiol Endocrinol Metab 279:E501-507. 'Beta(3)-adrenergic receptor activation of AOD-9604-induced lipolysis'. View Scientific Paper →
Kwon DR, Park GY. (2019) Cartilage. 'Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model'. View Scientific Paper →
Metabolic Pharmaceuticals corporate disclosure (2007) — Phase 2 12-week and 23-week clinical trial results in obese adults; obesity program halted due to modest efficacy. View Scientific Paper →
FDA GRAS Notice GRN 525 (2014) — AOD-9604 Generally Recognized as Safe status for use as a food ingredient. View Scientific Paper →
Ng FM, Bornstein J. (1978) Diabetes. 'Hyperglycemic action of synthetic C-terminal fragments of human growth hormone' — early mechanistic work on hGH fragments. View Scientific Paper →
Stier H, Vos E, Kenley D. (2013) Regul Toxicol Pharmacol. 'Safety and tolerability of the hexadecapeptide AOD9604 in humans' — pooled safety analysis of clinical-trial database. View Scientific Paper →