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| Sequence | Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe |
| Formula | C78H123N23O23S2 |
| Molar Mass | ~1815.1 g/mol |
| Category | hGH Fragment / Lipolytic Agent |
| Half-life | Short (< 30 min) |
| Admin | Subcutaneous, Intra-articular |
| FDA Status | Category 2 (Banned for compounding) |
| CAS | 221231-10-3 |
AOD-9604 is a synthetic peptide fragment comprising the C-terminal amino acids 177–191 of human growth hormone (hGH), modified with a tyrosine residue to enhance stability. Originally developed by Metabolic Pharmaceuticals to treat obesity, it was designed to isolate the fat-burning (lipolytic) properties of growth hormone without triggering its anabolic (growth-promoting) or glycemic effects. Despite failing late-stage clinical trials for weight loss, it remains a subject of interest for cartilage regeneration and off-label use.
What is it?
A specific fragment of the human growth hormone molecule (residues 177-191) with an added tyrosine amino acid. It represents the "fat-burning" domain of hGH but lacks the ability to stimulate IGF-1 or cause growth.
Primary Benefit
Originally targeted for weight loss, where it showed immense promise in animals but failed in human trials. It is now primarily investigated for cartilage repair and osteoarthritis relief, though human data is sparse.
Safety Profile
Caution (Yellow) to Restricted (Red)
While generally well-tolerated in clinical trials, the FDA has recently flagged it for potential immunogenicity risks and banned it from compounding pharmacies (Category 2). It is strictly prohibited by WADA for athletes.
| Variable | Recommendation |
|---|---|
| Common Dosage | 300 mcg (0.3 mg) per day |
| Frequency | Once daily, typically morning fasted |
| Cycle | 4–12 weeks |
| Route | Subcutaneous Injection (preferred) or Intra-articular |
Clinical Note: Oral administration was tested in trials but showed poor bioavailability compared to injection. Current "research" protocols almost exclusively use subcutaneous injection. Intra-articular injections are strictly for clinical settings.
The Theory: AOD-9604 binds to receptors on adipocytes (fat cells), triggering the release of stored fatty acids and inhibiting the accumulation of new fat.
The Pivot: After the obesity trials failed, researchers investigated AOD-9604 for musculoskeletal indications.
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| Sequence | Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe |
| Formula | C78H123N23O23S2 |
| Molar Mass | 1815.1 g/mol |
| Category | Growth Hormone Fragment |
| Half-life | Short (< 1 hour) |
| Admin | Subcutaneous Injection |
| FDA Status | Category 2 (Prohibited for Compounding) |
| CAS | 221231-10-3 |
AOD-9604 is a synthetic peptide fragment derived from the C-terminus of human growth hormone (hGH), specifically designed to isolate the fat-burning (lipolytic) properties of the hormone without its growth-promoting effects. Despite early promise in animal models and safety in human trials, it failed to demonstrate significant efficacy for weight loss in large-scale Phase 2b clinical trials and is currently prohibited for compounding by the FDA due to safety concerns.
Aliases
Key points
What people use it for
FDA Status: In September 2023, the FDA placed AOD-9604 on the Category 2 list of bulk drug substances. This classification indicates "significant safety risks" (specifically immunogenicity and peptide impurities). It is illegal for U.S. pharmacies to compound AOD-9604.[^5][^6]
WADA Status: PROHIBITED at all times (in and out of competition) under section S2. Peptide Hormones, Growth Factors, Related Substances, and Mimetics. Usage will result in a doping violation.[^7]
Regulatory classification
Geographic legal status
Sports and competition
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Source quality considerations
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Primary Targets
AOD-9604 does not bind to the full-length hGH receptor with high affinity. Instead, it is believed to act on a separate, specific metabolic receptor pathway.
Metabolic Effects
| Outcome | Magnitude | Evidence Quality | Consistency |
|---|---|---|---|
| Weight Loss | ↔ (Neutral) | [High (Negative)] | High |
| Glucose Safety | ↔ (Neutral) | [High] | High |
| Cartilage Repair | ? (Unknown) | [Very Low] | N/A |
| IGF-1 Elevation | ↔ (None) | [High] | High |
1. The OPTIONS Trial (Obesity)
2. The Kwon et al. Study (Cartilage)
In clinical trials involving over 900 human subjects, AOD-9604 was generally well-tolerated.
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AOD-9604 is a modified form of the C-terminal fragment of the human growth hormone (hGH) molecule. The full hGH protein is 191 amino acids long; the region responsible for fat burning is located at the very end (residues 177-191).
Note: The benefits listed below are largely theoretical or based on animal models. Human clinical trials failed to confirm the primary weight loss benefit.
The most touted benefit of AOD-9604 is its ability to target adipose tissue specifically.
Following the failure in obesity trials, research pivoted to musculoskeletal applications.
Unlike full-length hGH, AOD-9604 does not induce hyperglycemia or insulin resistance.
| Outcome / Goal | Effect* | Consistency** | Evidence quality | Trials*** | Notes (population, duration, dose) |
|---|---|---|---|---|---|
| Weight Loss (Obesity) | ↔ (no effect) | High | High | 1 Phase 2b RCT | 536 obese adults, 24 weeks. Failed to outperform placebo + diet/exercise.[8:3] |
| Safety / Tolerability | ↔ (safe) | High | Moderate | 6 Clinical Trials | Generally well-tolerated in trials up to 24 weeks. No IGF-1 elevation.[11:2] |
| Cartilage Repair | ? (unclear) | N/A | Very Low | 0 Human Trials | No human RCTs exist. Efficacy is based entirely on rabbit models.[4:4] |
| Glucose Tolerance | ↔ (neutral) | High | Moderate | 2 RCTs | Does not impair insulin sensitivity or glucose levels (unlike hGH).[11:3] |
*Effect: ↔ (no clear effect), ? (unclear/no data). Health impact: (p) = positive, (n) = negative.
**Consistency: High (trials agree), Low (conflict).
***Trials: Number of human clinical trials.
AOD-9604 functions by mimicking the lipolytic domain of the human growth hormone molecule while lacking the domain required for high-affinity binding to the hepatic growth hormone receptor.
AOD-9604 is typically supplied as a lyophilized (freeze-dried) white powder that must be reconstituted with bacteriostatic water.
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⚠️ CRITICAL REGULATORY INFORMATION
FDA Status (USA)
WADA Status (Sports)
Availability
Since pharmaceutical development was halted, no FDA-approved brand-name version exists. It is widely sold as a "research chemical" or "cosmetic peptide," but these products are not regulated for human safety or purity.
In the Metabolic Pharmaceuticals trials, doses ranged from 0.25 mg to 1 mg daily.
Users in the body composition community often follow this protocol, though it is not validated by successful trials:
In clinical trials involving over 900 patients, AOD-9604 was generally well-tolerated with a safety profile similar to placebo[11:4].
Despite the clean trial data from 2007, the FDA raised significant flags in 2023/2024 regarding compounded injectables[6:3][9:3].
Note: These combinations are purely anecdotal and lack clinical validation.
1. Did AOD-9604 actually work for weight loss in trials?
No. In the definitive Phase 2b trial (OPTIONS study), it failed to produce more weight loss than placebo. Both groups lost weight due to diet and exercise, but the drug added no extra benefit[8:5].
2. Why is it banned by the FDA for compounding if it was "safe" in trials?
The FDA distinguishes between "safe to eat" (GRAS food status) and "safe to inject." The recent ban is based on the risk of impurities and immunogenicity (antibody attacks) associated with injectable peptides that haven't gone through the rigorous modern drug approval process[9:4].
3. Will AOD-9604 show up on a drug test?
Yes. WADA-accredited laboratories have sensitive tests for AOD-9604. It is banned for athletes at all times. Standard employment drug screens (5-panel, 10-panel) typically do not test for peptides, but sports anti-doping panels do.
4. Can I take it orally?
Technically yes, but bioavailability is very poor for standard peptide powders. The clinical trials used a specialized protected formulation, and even then, efficacy was lacking. Injection is the only reliable method for delivery, though efficacy remains unproven.
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Heffernan M, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001;142(12):5182-9. https://pubmed.ncbi.nlm.nih.gov/11713213/ ↩︎
Heffernan M, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism. Endocrinology. 2001. https://pubmed.ncbi.nlm.nih.gov/11713213/ ↩︎ ↩︎
Ng FM, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research. 2000;53(6):274-278. https://doi.org/10.1159/000023592 ↩︎ ↩︎ ↩︎
Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Annals of Clinical and Laboratory Science. 2015;45(4):426-432. http://www.annclinlabsci.org/content/45/4/426.long ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Kim KS, et al. The effects of AOD9604 on the regeneration of damaged cartilage. Journal of Orthopaedic Research. 2015. https://downloads.regulations.gov/FDA-2024-N-4777-0002/attachment_17.pdf ↩︎
U.S. Food and Drug Administration. Safety Risks Associated with Certain Bulk Drug Substances Nominated for Use in Compounding. FDA.gov. 2023. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks ↩︎ ↩︎ ↩︎ ↩︎
Heffernan M, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001;142(12):5182-5189. https://doi.org/10.1210/endo.142.12.8522 ↩︎ ↩︎ ↩︎
Metabolic Pharmaceuticals Limited. Metabolic's obesity drug - Phase 2B clinical trial results. ASX Announcement. 2007. https://www.sec.gov/Archives/edgar/vprr/0702/07021963.pdf ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee (PCAC) Meeting Materials. December 2024. https://www.fda.gov/advisory-committees/pharmacy-compounding-advisory-committee/2024-meeting-materials-pharmacy-compounding-advisory-committee ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Biotech Peptides. (2024). AOD 9604 Research into Fat Cell Metabolism and Lipolysis. https://biotechpeptides.com/2024/10/22/aod-9604-research-into-fat-cell-metabolism-and-lipolysis/ ↩︎
Stier H, Vos E, Kenley D. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism. 2013;3(1-2):7-15. https://www.jofem.org/index.php/jofem/article/view/157/194 ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Ng FM. Structural modification of the C-terminal domain of human growth hormone: biological and immunological properties. Journal of Endocrinology. 2002. ↩︎
Restore Health Consulting. (2023). FDA Adds Several Peptides to Category 2 Bulks List. https://www.restorehealthconsulting.com/news/fda-adds-several-peptides-to-category-2-bulks-list-restricting-them-from-compounding ↩︎
World Anti-Doping Agency. Prohibited List. S2. Peptide Hormones, Growth Factors, Related Substances, and Mimetics. https://www.wada-ama.org/en/prohibited-list ↩︎
World Anti-Doping Agency. (2019). Prohibited List. https://www.wada-ama.org/en/prohibited-list ↩︎
Drugs.com. (n.d.). WADA Prohibited List S2. https://www.drugs.com/wada/s2-peptide-hormones-growth-factors-and-related-substances.html
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