AOD-9604
Tyr-hGH(177-191), AOD9604, modified growth hormone C-terminal fragment
AOD-9604 is a 16-amino-acid fragment of the tail end of human growth hormone, developed in Australia in the 1990s on the theory that it carries growth hormone's fat-burning effect without its growth-promoting effects. It reached a large human obesity trial and failed it. Development as a drug was abandoned in 2007, and it is now sold as a supplement ingredient and a grey-market injectable on the strength of evidence that did not survive proper testing.
Mechanism
AOD-9604 derives from the C-terminal region of human growth hormone. The underlying hypothesis, developed by Frank Ng and colleagues at Monash University from the 1970s onwards, was that growth hormone's lipolytic activity is structurally separable from its growth-promoting activity: the anabolic effects run through the growth hormone receptor and downstream IGF-1, while the fat-mobilising effects were proposed to reside in a distinct C-terminal domain. If true, a fragment containing only that domain would reduce fat without raising IGF-1, without insulin resistance, and without the tissue overgrowth that limits growth hormone use.
In rodent work, the fragment increased lipolysis in adipose tissue, increased fat oxidation, reduced lipogenesis and reduced body weight, apparently without changing IGF-1. Mechanistically it was proposed to act by increasing beta-3 adrenergic receptor expression in adipose tissue. That proposal was subsequently undermined by the researchers' own data: the compound retained activity in beta-3 adrenergic receptor knockout mice, meaning beta-3 signalling cannot be the required pathway. No specific receptor for AOD-9604 has ever been identified. Two decades after the mechanistic work began, there is no validated molecular target, and the mechanism as usually stated on vendor websites is a hypothesis that the primary literature has already partly falsified.
What the research shows
The preclinical package is real but modest and confined to rodents and isolated tissue, largely from a single research group with a commercial interest in the outcome. The human story is where the honest account diverges sharply from the marketing. A 12-week phase 2 trial reported by the developer, Metabolic Pharmaceuticals, generated the figure still quoted today: participants on the 1 mg dose lost about 2.8 kg against 0.8 kg on placebo. That result was announced in 2004 and received substantial press coverage.
The follow-up pivotal trial is the part that is rarely mentioned. A larger phase 2b study, run over 24 weeks in several hundred participants using oral administration, failed to demonstrate statistically significant weight loss against placebo at any dose tested, and Metabolic Pharmaceuticals halted the obesity drug development programme in 2007. That negative trial has never, to the best of what can be established from the indexed literature, been published in a peer-reviewed journal; its design details survive only in company and stock-exchange disclosures and contemporaneous trade press, which is why this library records them as unverified. The result is a textbook case of publication asymmetry: the encouraging small result circulated widely and permanently, while the definitive negative result exists only in corporate filings.
What remains in the peer-reviewed record for humans is thin. A 2013 pooled safety and tolerability review concluded AOD9604 was well tolerated and did not raise IGF-1, but it was published in a journal not indexed in PubMed and was produced in connection with the compound's repositioning as a food ingredient. A separate 2015 study examined intra-articular injection for osteoarthritis in a RABBIT model, not in humans, and concerns an entirely different indication. There is no adequately powered, peer-reviewed, published randomised controlled trial demonstrating that AOD-9604 reduces body weight or fat mass in humans. Anyone selling it for fat loss is selling a compound that was tested for exactly that purpose and did not work.
Evidence assessment
Limited evidence
Human trials exist, so this is not a purely preclinical compound, but the one adequately powered obesity study was negative and was never published; the only supporting positive human data appear in a non-indexed journal produced by parties connected to the compound's commercial sponsors, and no peer-reviewed randomised trial demonstrates efficacy for fat loss. The tier reflects the existence of human testing, not its success.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Hyperglycemic action of synthetic C-terminal fragments of human growth hormone Preclinical only
Reported that C-terminal fragments of human growth hormone possess metabolic activity distinct from the intact hormone, the observation on which the AOD-9604 development programme was later built.
Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism Preclinical only
The synthetic growth hormone fragment increased lipolysis and fat oxidation in rodents following oral administration.
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 Preclinical only
AOD9604 reduced body weight and increased fat oxidation in obese mice, and retained activity in beta-3 adrenergic receptor knockout animals.
Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone Preclinical only
Characterised the lipolytic activity of AOD9604 and reported an absence of effect on IGF-1, supporting separation of lipolytic from growth-promoting activity.
Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans Limited evidence
AOD9604 was reported as well tolerated with an adverse event profile indistinguishable from placebo and no effect on serum IGF-1 levels.
Phase 2b obesity trial of AOD9604 (unpublished; sponsor-reported) Limited evidence
Failed to demonstrate statistically significant weight loss versus placebo at any dose tested, after which the sponsor halted obesity drug development for AOD9604.
Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model Preclinical only
Reported cartilage effects following intra-articular injection in a rabbit model, an indication unrelated to fat loss.
Safety
The available human data suggest AOD-9604 is well tolerated at the doses studied, with an adverse event profile reported as indistinguishable from placebo and, importantly, no elevation of IGF-1, which is consistent with it not acting through the growth hormone receptor. That much is genuinely reassuring as far as it goes. The limits of that reassurance need stating plainly. The safety data come predominantly from short trials, the most-cited of which was published outside the peer-reviewed indexed literature by parties connected to the compound's commercial development. A further mismatch is rarely acknowledged: the substantive human trials used oral administration, whereas the grey market sells the peptide for injection, so the tolerability record does not straightforwardly transfer to how the compound is actually being used. No long-term safety data exist in any population. Nothing is known about use in pregnancy, adolescence, or alongside other agents. Most importantly, essentially all of the material sold to consumers is not the pharmaceutical-grade peptide used in those trials: it is grey-market synthesis of unverified identity, purity and concentration, frequently mislabelled and not meaningfully distinguished from hGH fragment 176-191. Analytical surveys of illicit peptide products have repeatedly found content that does not match the label. The safety record of the studied compound tells you very little about the safety of what is actually in the vial.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | Not licensed by the MHRA for any indication. It is not an authorised medicine, and it does not have authorised novel food status for use as a food ingredient in Great Britain. Supplying it for human use with therapeutic claims would fall outside the Human Medicines Regulations 2012. |
| United States | Not approved as a drug for any indication. Drug development for obesity was abandoned in 2007. It was subsequently repositioned as a food and supplement ingredient on the basis of a self-affirmed GRAS determination, a route that does not involve FDA efficacy review. AOD-9604 was nominated for the FDA's section 503A bulk drug substances list and placed in Category 2 (substances that may present significant safety risks); FDA announced its removal from Category 2 on 20 September 2024, effective 27 September 2024, following withdrawal of the nomination by the nominators. Removal from Category 2 on those grounds does not authorise compounding and is not a safety clearance. Marketing it as a drug for fat loss makes it an unapproved new drug. |
| WADA (sport) | Prohibited at all times. AOD-9604 is explicitly named in section S2.2.3 of the WADA Prohibited List under growth hormone fragments, as a non-specified substance. Its detection in athlete supplements was central to a major Australian sports doping investigation. |
Questions
There is no adequately powered, peer-reviewed randomised trial showing that it does. A small 12-week study reported about 2.8 kg loss versus 0.8 kg on placebo and generated lasting publicity. The larger 24-week phase 2b trial designed to confirm it failed to show significant weight loss at any dose, and the developer terminated the obesity programme in 2007. That negative trial was never published, which is why the encouraging figure still circulates unchallenged.
In sequence terms, yes. AOD-9604 is described as a tyrosine attached to hGH 177-191, giving YLRIVQCRSVEGSCGF. Because residue 176 of human growth hormone is itself a tyrosine, that construct reconstitutes native hGH(176-191) exactly, so the two names denote the same 16-residue peptide. The draft version of this page hedged on whether they are chemically identical; on the sequence, they are. Vendors nonetheless sell them as separate products, and since neither is manufactured to any standard, a vial labelled as either could contain either, or neither.
The available human data indicate it does not raise serum IGF-1, which is consistent with it not acting through the growth hormone receptor. That is the one claim about AOD-9604 that the evidence reasonably supports. It is worth noting that this same finding is also consistent with the compound simply not doing very much, which is what the failed pivotal trial suggested.
Because that phrase is a legal shield, not a scientific statement. Labelling an unapproved compound 'for research use only' or 'not for human consumption' lets sellers distribute material to consumers while nominally disclaiming that it is a drug. It says nothing about purity, identity, dose accuracy or safety, and it does not mean any research is being conducted. For athletes there is a further consequence: AOD-9604 is explicitly named on the WADA Prohibited List.