PreclinicalLongevity & MetabolicTrial failure

AOD-9604

A 16-amino-acid C-terminal fragment of human growth hormone · the "lipolytic fragment"

Overview

AOD-9604 is a synthetic fragment of human growth hormone (residues 176–191) originally developed by Metabolic Pharmaceuticals as an anti-obesity drug. Its own Phase 2 human trials failed to show significant weight loss versus placebo, and development was effectively halted. It is not approved as a medicine anywhere; today it lives on as a research-chemical sold for fat loss on weak evidence.

01 What is AOD-9604?

In plain English.

AOD-9604 is a lab-made peptide copied from the tail end of human growth hormone, specifically the last 16 amino acids of the molecule, residues 176 to 191. In the 1990s a group at Monash University proposed that this small "lipolytic" tail carried most of growth hormone's fat-burning effect without its growth-promoting side. Metabolic Pharmaceuticals, an Australian biotech, licensed the work and developed AOD-9604 as a candidate anti-obesity drug.

⏱ Half-life
Short (minutes, est.)
☉ Route
Subcutaneous / oral (trialled)
⚖ Evidence
Failed Phase 2
📚 Studies
7 referenced

That development programme is over. The drug was taken through human clinical trials, those trials did not meet their endpoints, and Metabolic abandoned the obesity indication. The vials sold online today are the leftover idea, the peptide its own developer tried and failed to turn into a medicine.

02 How it works

The simple version, then the science.

In the original mouse work, AOD-9604 increased fat breakdown (lipolysis) and reduced fat storage (lipogenesis), apparently without the blood-sugar and growth effects of the full growth hormone molecule. The pitch was elegant: a "GH-like fat-burner" that wouldn't cause insulin resistance or acromegaly. In humans, that pitch did not hold up at the clinical-endpoint level.

Go deeper · the proposed mechanism

Ng and colleagues at Monash mapped the lipolytic activity of growth hormone to its C-terminal domain and proposed AOD-9604 as a stabilised mimic. In rodents, Heffernan et al. reported reduced body weight and increased fat oxidation after chronic treatment with the fragment, with effects that appeared partly independent of the β3-adrenergic receptor. The proposed mechanism involves upregulation of β3-AR expression and direct stimulation of lipolysis in adipocytes. None of this has been confirmed at clinically meaningful magnitudes in humans.

03 What it's used for

Each use graded by how strong the evidence actually is.

  • Limited
    Obesity / weight lossThe original indication. Phase 2 trials in obese adults did not show a clinically meaningful weight-loss advantage over placebo, and Metabolic Pharmaceuticals halted the obesity programme. Despite this, fat loss remains the dominant online marketing claim.
  • Preclinical
    Lipolysis & fat oxidationReproducible effects in rodent studies (Heffernan, Ng et al.), increased fat oxidation, reduced body weight in obese mice. Read-across to humans was the basis of the failed trials.
  • Preclinical
    Cartilage repair / osteoarthritisA 2015 rabbit study (Kwon & Park) reported that intra-articular AOD-9604, especially with hyaluronic acid, improved cartilage outcomes in a collagenase-induced osteoarthritis model. Animal only; no human trials.
  • Anecdotal
    Body recomposition in gym communitiesMarketed alongside CJC-1295/ipamorelin stacks as a "fat-burning" peptide. Not supported by controlled human data.
The headline use failed its own trial. AOD-9604 was developed as an anti-obesity drug and its Phase 2 human studies did not show significant weight loss vs placebo. Any current "fat-loss peptide" marketing is selling a result that the original sponsor could not demonstrate.

04 What the evidence says

AOD-9604's evidence base is unusual: it has more animal data than most research-chemical peptides, and it has actual human trials, which is rare in this space, but those human trials were unflattering. The rodent literature (Ng 2000; Heffernan 2000, 2001) is consistent: the fragment increases fat oxidation and reduces weight in obese mice. The translation problem hit in humans. Metabolic Pharmaceuticals progressed AOD-9604 through Phase 1 and into Phase 2 obesity trials in the mid-2000s; the compound was well-tolerated, but the weight-loss signal versus placebo was not clinically meaningful, and Metabolic discontinued the obesity programme. No Phase 3 trial was ever run. A small later study (Kwon & Park, 2015) suggested possible cartilage-repair effects in rabbit knees, which is where some of the modern "joint" marketing comes from, but again, no human trials. Honest summary: a drug candidate that did not work as advertised, kept alive by the research-chemical market.

05 Dosing & administration

Reported in the literature, information not advice.

Because the obesity programme failed and AOD-9604 is not an approved medicine, there is no clinically sanctioned dose. The trial literature used both oral and subcutaneous formulations in the milligram range. Online vendors describe daily subcutaneous microgram-to-milligram regimens, but these are not based on a successful clinical protocol and the purity of research-grade vials is unregulated. Anyone considering use should speak to a clinician.

06 Side effects & safety

Across Metabolic Pharmaceuticals' clinical programme, AOD-9604 was reported as well-tolerated, its problem was efficacy, not acute safety. That said, long-term safety in humans is genuinely unknown: no large trial was ever run because the drug did not work, and the people now injecting it are not being monitored. Reported short-term effects in users include injection-site reactions and mild GI upset. Because the fragment is derived from growth hormone, theoretical concerns around insulin sensitivity, IGF-1 signalling and any cancer history are reasonable, even though the trials did not flag them at the doses tested. Products sold as "AOD-9604" are unregulated research chemicals, purity, identity and contamination cannot be assumed. People who are pregnant, breastfeeding, immunocompromised, taking other medicines, or with a history of cancer should be especially cautious.

Not an approved medicine anywhere. AOD-9604 failed Phase 2 in obesity and was never approved. WADA prohibits growth-hormone-related peptides at all times under S2, AOD-9604 falls within the catch-all for GH fragments and mimetics.

07 Where to buy (research use only)

Vetted on quality and transparency, not an endorsement to use.

Helix Research Labs4.6
Research-use-only peptides with publicly available certificates of analysis.
HPLC & MS verifiedPublished COAsResearch use only
View ↗
Apex Compounds4.3
Competitive pricing across a broad range of research compounds.
Third-party testedResearch use only
View ↗
Vanta Bio4.5
Specialist supplier with independent lab testing on every batch.
Independent lab testingResearch use only
View ↗
Disclosure: Pepwyse is not affiliated with these companies and does not earn any commission from these links; they are listed for reference only. These products are sold strictly for laboratory research use only and are not for human consumption.

09 Clinical studies & research

Primary sources. Read the science yourself.

Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone
Hormone Research · 2000 Preclinical · review
Foundational Monash paper from Ng and colleagues mapping the lipolytic activity of growth hormone to its C-terminal domain and introducing AOD-9604. The scientific basis of the whole programme. View on PubMed →
Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism
American Journal of Physiology, Endocrinology and Metabolism · 2000 Animal (mouse)
Heffernan et al. show that oral administration of a hGH C-terminal fragment reduces weight gain and increases fat metabolism in mice, the rodent result that drove human-trial ambitions. View on PubMed →
Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment
International Journal of Obesity and Related Metabolic Disorders · 2001 Animal (obese mice)
Chronic treatment with AOD-9604 increased fat oxidation and reduced weight in obese mice without the glycaemic side-effects of full growth hormone. Reproducible preclinical signal that did not survive translation. View on PubMed →
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 Animal (mouse, knockout)
Heffernan et al. dissect the mechanism: AOD-9604 acts partly via β3-adrenergic receptor pathways but also through receptor-independent routes. Mechanistic backbone of the developer's case. View on PubMed →
AOD-9604
Current Opinion in Investigational Drugs · 2004 Drug-development review
Wilding's contemporary review of Metabolic Pharmaceuticals' development programme, written while Phase IIa trials were underway. Useful as a snapshot of what the sponsor was claiming before the trials reported out. View on PubMed →
Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model
Annals of Clinical and Laboratory Science · 2015 Animal (rabbit)
Kwon & Park report that intra-articular AOD-9604, particularly combined with hyaluronic acid, improved cartilage outcomes in a collagenase-induced rabbit knee model. The basis of modern "joint repair" claims, animal only. View on PubMed →
AOD-9604 does not influence the WADA hGH isoform immunoassay
Drug Testing and Analysis · 2013 Analytical · doping
Orlovius et al. show that AOD-9604 is not picked up by the standard WADA growth-hormone isoform immunoassay, relevant because it means the catch-all S2 prohibition is the operative anti-doping route, not the routine hGH test. View on PubMed →

10 Frequently asked questions

Did AOD-9604 actually work for weight loss?
Not in humans. The compound was developed specifically as an anti-obesity drug by Metabolic Pharmaceuticals, and its Phase 2 trials in obese adults did not show a clinically meaningful weight-loss advantage over placebo. The sponsor discontinued the obesity programme. Animal data in obese mice is genuinely positive, but it did not translate.
Is AOD-9604 the same thing as growth hormone?
No. AOD-9604 is a 16-amino-acid synthetic fragment of growth hormone, the last 16 residues (176–191), known as the "lipolytic tail". Full hGH is 191 [amino acids](/glossary "Amino acid: The building blocks of proteins. A peptide is a short chain of them linked together.") and has many actions; AOD-9604 was designed to keep only the fat-burning ones. Whether it actually does that in humans was the question Phase 2 was meant to answer, and the answer was effectively no.
Is AOD-9604 approved by any regulator?
No. AOD-9604 is not approved as a medicine in the UK, US, EU, Canada or Australia. The FDA has not authorised it, and it is not on the FDA's lists of bulk substances permitted for pharmacy compounding. It is sold only as a research chemical.
Is AOD-9604 banned in sport?
Yes, by category. The WADA Prohibited List bans growth-hormone-related peptides, fragments and mimetics at all times under S2. AOD-9604 is a growth-hormone fragment, so it falls inside that prohibition. Detection is a separate question: routine hGH immunoassays don't pick it up, so a targeted test is needed.
Is AOD-9604 safe?
In the trials Metabolic Pharmaceuticals ran, it was reported as well-tolerated, its failure was about efficacy, not acute safety. But long-term human safety is unknown, because no large or long study was ever done. Products sold online are unregulated research chemicals; purity and identity cannot be assumed.
Peppy
AI · knows this page
Hi, I'm Peppy, an AI assistant. Ask me anything about AOD-9604 or any peptide.
Did AOD-9604 work for weight loss?Why did the obesity trials fail?Is AOD-9604 the same as growth hormone?
Peppy is an AI, not a doctor. Information only, every question is logged to improve our content.