Home / Compounds / AOD-9604
Metabolic Research

AOD-9604 Growth Hormone Fragment 176–191

A synthetic peptide fragment of human growth hormone designed to isolate lipolytic activity without growth-promoting or diabetogenic effects. Development terminated in 2007 after Phase IIb clinical trial failure.
⚠️

Regulatory status: AOD-9604 failed its pivotal clinical trial for fat loss and was discontinued in 2007. In December 2024, the FDA determined AOD-9604 should not be included on the 503A bulks list for compounding. It is not FDA-approved for any indication.

Overview

AOD-9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino acid peptide fragment corresponding to amino acids 176–191 of human growth hormone, with a stabilizing tyrosine substitution at the N-terminus. It was developed by Metabolic Pharmaceuticals Ltd. in Australia during the 1990s in collaboration with researchers at Monash University.

The hypothesis was elegant: isolate the fat-metabolizing domain of growth hormone while removing the regions responsible for IGF-1 elevation, insulin resistance, and tissue growth. In rodent models, this worked. AOD-9604 reduced body weight in genetically obese mice without the adverse metabolic effects of full-length growth hormone. The compound advanced into human trials.

The human trials failed. A Phase IIb study enrolling over 300 obese subjects over 24 weeks did not meet its primary endpoint of statistically significant weight loss compared to placebo. The effect size was clinically negligible — approximately 2.6 kg vs. 0.8 kg. Development was terminated in 2007. Despite this, AOD-9604 became one of the most widely marketed grey-market peptides, sold with fat-loss claims that its own clinical data does not support.

Dosage & Reconstitution

Vial strength
5 mg
BAC water added
3 mL
Final concentration
~1.67 mg/mL
WeeksDosageSyringe units (U-100)
Weeks 1–40.3 mg18 units0.18 mL
Weeks 5–120.5 mg30 units0.3 mL

FrequencyOnce daily, subcutaneous, in the morning before eating.

Note

For review — not established human dosing. The one human trial of AOD-9604 that reported an amount used an oral 1 mg capsule and did not beat placebo. The injectable week ranges and amounts in the chart follow a circulated research protocol, not that trial. The concentration strip above the chart is calculated from the vial and water volume and is correct.

Unverified — no cited human study establishes a subcutaneous frequency for AOD-9604.

AOD-9604's only human trial was oral — 1 mg a day in 300 adults with obesity, and it missed its primary endpoint at 24 weeks — so the subcutaneous amounts charted here are not the amounts that were studied, and they are flagged for review rather than presented as established dosing. Athena lists one strength: a 5 mg vial made up with 3 mL comes to about 1.67 mg/mL, so the 0.3 mg starting step is 18 units and the 0.5 mg step is 30 units, both inside a single 50-unit syringe. AOD-9604 is a fragment of human growth hormone that does not raise IGF-1, so findings reported for growth hormone itself do not carry across to it.

What this evidence establishes. AOD-9604 has been studied in humans, but the trial that reported a dose used an oral formulation and did not reach its primary endpoint against placebo at 24 weeks. No injectable human dosing has been established in the published literature, so the reconstitution figures below are arithmetic only and are not tied to any studied injectable dose.

Sources: Phase IIa obesity trial (n=300), 2003–2005, reported on this site's AOD-9604 profile

For educational and laboratory research purposes only. It does not provide medical advice, dosing recommendations, or instructions for human or veterinary use. Syringe units assume a U-100 syringe, on which 1 mL is 100 units and a 50-unit syringe holds 0.5 mL.

Mechanism of Action

AOD-9604 targets adipose tissue metabolism through a mechanism distinct from full-length growth hormone:

🔥

Lipolysis Stimulation

Promotes breakdown of stored triglycerides in adipose tissue through β-adrenergic pathway interactions

🚫

Anti-Lipogenic

Inhibits formation of new fat — reducing both fat storage and fat cell proliferation in preclinical models

⚖️

No IGF-1 Elevation

Does not activate the GH receptor or raise IGF-1 levels — distinguishing it from full-length growth hormone

🧬

Receptor-Independent

Fat-metabolizing effects appear to occur through a non-GH-receptor mechanism that remains incompletely characterized

🦴

Cartilage Interest

Post-failure pivot to cartilage repair applications led to TGA approval in Australia for osteoarthritis formulations

📉

Glucose Neutral

No effect on blood glucose or insulin sensitivity observed in clinical trials — a safety advantage over full-length GH

Research Timeline

1990s
Development at Monash University
Professor Frank Ng and colleagues at Monash University identify the C-terminal fragment of human growth hormone as the lipolytic domain. Metabolic Pharmaceuticals licenses the compound.
2000
Preclinical Success
Ng et al. publish that AOD-9604 reduces body weight gain by over 50% in obese Zucker rats with no adverse effects on glucose tolerance, insulin sensitivity, or IGF-1 levels.
2001
Mechanism Published
Heffernan et al. publish in Endocrine Journal demonstrating selective lipolytic activity. Compound enters human clinical development.
2003–2005
Phase IIa — Modest Signal
A 12-week Phase IIa trial in 300 obese participants shows AOD-9604 (1 mg/day oral) produces 2.6 kg weight loss vs. 0.8 kg placebo. Modest but encouraging enough to proceed.
2006–2007
Phase IIb — Primary Endpoint Failed
A 24-week Phase IIb trial in 536 obese subjects fails to demonstrate statistically significant weight loss compared to placebo. Confidence intervals cross zero. Development terminated.
2007
Development Abandoned for Obesity
Metabolic Pharmaceuticals discontinues all obesity development. Pivots to exploring osteoarthritis/cartilage repair applications.
2021
GRAS Status as Food Ingredient
AOD-9604 receives Generally Recognized As Safe (GRAS) status from the FDA as a food ingredient — not as a therapeutic agent. This is frequently misrepresented as FDA "approval."
2023
FDA Category 2 Designation
FDA classifies AOD-9604 as a Category 2 bulk drug substance with safety concerns, prohibiting compounding for human use.
2024 (Sept)
Removed from Category 2
AOD-9604 is removed from Category 2 after nominators withdraw their submissions. This does NOT mean it was cleared for compounding — it entered a new review process.
2024 (Dec)
FDA Recommends Against 503A Inclusion
At the December 2024 PCAC meeting, the FDA recommends AOD-9604 not be included on the 503A bulks list, citing limited long-term safety data, peptide impurities, and immunogenicity concerns.

Contraindications & Safety Data

AOD-9604 has the most extensive human safety database of any discontinued research peptide — over 900 participants across six controlled trials. Adverse events were generally mild and comparable to placebo. However, efficacy failure and regulatory exclusion make the risk-benefit calculation unfavorable.

Condition / FactorRisk LevelRationale
Active cancer or malignancyMODERATEAlthough AOD-9604 does not elevate IGF-1, the GH-fragment mechanism warrants caution in patients with active malignancy
Pregnancy / breastfeedingHIGHNo reproductive toxicology data available for AOD-9604 in human pregnancy
Immunogenicity riskMODERATEFDA cites immunogenicity as a specific concern. Peptide impurities may trigger immune reactions
Hypoglycemia riskLOWOccasional reports of non-specific hypoglycemia in clinical trials, though glucose-neutral profile was generally confirmed
Cardiovascular conditionsLOWNo cardiovascular signals detected across 6 clinical trials and ~900 subjects
Use for weight lossEVIDENCE FAILEDThe compound failed its pivotal Phase IIb trial for this exact indication. Marketing claims for fat loss are not supported by the clinical data.
Grey-market sourcingHIGHUnregulated products carry contamination, mislabeling, and impurity risks on top of a compound that already failed its efficacy trial

Regulatory Status

FDA: AOD-9604 is not FDA-approved for any therapeutic indication. Development was terminated in 2007 after Phase IIb failure. In December 2024, the FDA recommended against including AOD-9604 on the 503A bulks list for compounding, citing safety concerns including immunogenicity and insufficient long-term data. GRAS status as a food ingredient (2021) does not constitute therapeutic approval.

WADA: Classified as a prohibited substance under S2 (peptide hormones and growth factors). Banned in and out of competition.

TGA (Australia): Approved for use in specific cartilage repair formulations — not for fat loss or metabolic applications.

The critical point: AOD-9604 is the rare case where extensive human data exists — and the data shows the compound doesn't work for its marketed indication. Over 900 clinical trial participants. Six controlled trials. Primary endpoint failed. This is not a compound lacking evidence. It's a compound whose evidence is negative.

References (APA 7th Edition)

Heffernan, M. A., Jiang, W. J., Thorburn, A. W., & Ng, F. M. (2000). Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. American Journal of Physiology-Endocrinology and Metabolism, 279(3), E501–E507.
Heffernan, M., et al. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and Zucker rats. Endocrine Journal, 48(Suppl), S35–S38.
Ng, F. M., Sun, J., Sharma, L., Libinaki, R., Jiang, W. J., & Gianello, R. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research, 53(5), 274–278.
U.S. Food and Drug Administration. (2024, December 4). Pharmacy Compounding Advisory Committee: AOD-9604 briefing document. FDA.
U.S. Food and Drug Administration. (2024). Bulk drug substances nominated for use in compounding: AOD-9604 determination. FDA.
Misra, M. (2013). Obesity pharmacotherapy: Current perspectives and future directions. Journal of Pharmacology and Pharmacotherapeutics, 4(2), 118–129.
Cox, H. D., Hughes, C. M., & Eichner, D. (2014). Detection and in vitro metabolism of AOD9604. Drug Testing and Analysis, 6(Suppl 1), 34–38.
World Anti-Doping Agency. (2024). The 2025 World Anti-Doping Code International Standard: Prohibited List. WADA.

AOD-9604 Research Readiness Quiz

Test your understanding of AOD-9604's evidence base, regulatory status, and clinical trial history.

Educational Disclaimer

This profile is for educational and research purposes only. It is not medical advice, and nothing on it is a protocol, a recommendation, or an instruction for use in a person or an animal.

Athena Peptides Education does not prescribe, sell, or recommend any compound. Compounds discussed here are for laboratory research only and are not for human consumption. Always consult a qualified physician before making any decision about your health.