D tier · weak
AOD9604 is unusual among low-tier compounds in having genuine randomised human data — roughly 900 subjects across six placebo-controlled trials — and that data is what condemns it: the modest 12-week signal did not survive a longer confirmatory trial, development was terminated in 2007, and everything since has been repositioning rather than new efficacy evidence.
aod-9604
AOD9604 is a 16-amino-acid analogue of the C-terminal lipolytic domain of human growth hormone, developed as an oral anti-obesity agent and taken through six randomised placebo-controlled trials totalling around 893 adults. It was consistently well tolerated and did not affect IGF-1 or carbohydrate metabolism, but a 12-week signal of roughly 2.6 kg versus 0.8 kg on placebo failed to replicate in a subsequent 24-week study and development was terminated in 2007.
// we supply this one
available as a research reagent
≥ 99% HPLC · lyophilised powder · batch certificate published. Grade D above is our own and is not adjusted because we stock it.
the explanation
AOD9604 is a small piece of the growth hormone molecule that was supposed to burn fat without growth hormone's downsides. It was genuinely tested in large human trials — and it lost: the longer, more rigorous study showed it did not work, and the company shut the programme down in 2007.
regulatory status
Not approved as a drug in any jurisdiction; development terminated 2007
The frequently cited 2014 'GRAS status' is a self-affirmed generally-recognised-as-safe determination for use as a food and supplement ingredient — a food-safety conclusion, not a weight-loss approval, and no corresponding GRAS notice appears in FDA's public GRAS Notice Inventory; separately, the nomination of AOD-9604 acetate as a bulk drug substance for compounding was withdrawn, and WADA prohibits it under S.0 (non-approved substances) because it has 'no current approval by any governmental regulatory health authority for human therapeutic use'.
how it works · proposed mechanism
AOD9604 was designed to isolate growth hormone's fat-mobilising domain from its growth-promoting and diabetogenic ones — an elegant hypothesis that human trials did not vindicate.
hGH receptor is not involved
AOD9604 does not bind or signal through the growth hormone receptor, which is why it leaves IGF-1 concentrations unchanged in humans. This is the compound's genuine and reproducible pharmacological distinction from hGH.
Beta-3 adrenoceptor upregulation
In obese mice, chronic AOD9604 increased fat oxidation and lipolytic markers and reduced body weight gain over 14 days, with the effect linked to increased beta-3 adrenergic receptor expression in adipose tissue. Humans express far less functional beta-3 adrenoceptor in adipose tissue than rodents, which is a plausible reason the mouse effect did not translate.
No carbohydrate penalty
Unlike intact hGH, AOD9604 did not induce hyperglycaemia in mice and showed no negative effect on carbohydrate metabolism across the human trial programme. The safety separation from hGH is real — it is the efficacy that failed.
Oral, not injectable, evidence
The phase 2b programme dosed AOD9604 orally at 0.25, 0.5 and 1 mg/day. The subcutaneous administration used in grey-market practice has no controlled human efficacy or safety data behind it at all.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
AOD9604 is the rare grey-market compound that was properly tested and properly failed: a 536-subject 12-week phase 2b produced about 1.8 kg of placebo-adjusted weight loss, and a subsequent 24-week trial that added a diet and exercise regime showed no weight-loss effect at all, after which development was terminated in 2007. Its safety record is genuinely clean, but a clean safety record on an ineffective drug is not a reason to use it — and every gram of that record was earned orally, not by injection.
key published findings
- Human phase 2b trial (536 subjects, 12 weeks, oral 0.25/0.5/1 mg daily): subjects on 1 mg/day lost an average of 2.6 kg versus 0.8 kg on placebo, and safety and tolerability showed 'no evidence of any difference between placebo' — a placebo-adjusted difference of roughly 1.8 kg over three months.
- Human confirmatory trial (24 weeks, second oral phase 2b of the two studies enrolling 300 and 500 obese adults): the weight-loss effect seen in earlier trials 'were not seen in the last study in which an intensive diet and exercise regime was incorporated' (Moré & Kenley 2014); development of AOD9604 was terminated in 2007.
- Human safety pool (Stier 2013, six randomised double-blind placebo-controlled trials, 893 adults): no serious adverse event related to AOD9604 intake, no withdrawals attributed to the drug, no anti-AOD9604 antibodies detected, no effect on IGF-1 levels and no negative effect on carbohydrate metabolism — in contrast to intact hGH.
- Rodent (Heffernan 2001, Int J Obes, obese mice, 14 days): both hGH and AOD9604 significantly reduced body weight gain with increased fat oxidation and lipolytic markers, but AOD9604 produced these effects without hGH's hyperglycaemia and without interacting with the hGH receptor.
- Rabbit (Kwon & Park 2015, Ann Clin Lab Sci, n=32, collagenase-induced osteoarthritis): intra-articular AOD9604 combined with hyaluronic acid outperformed either agent alone on lameness duration and cartilage regeneration scores — the basis for the joint-health repositioning claims, and an entirely preclinical, intra-articular finding.
- Forensic (Vanhee 2014, Drug Test Anal): AOD9604 was identified and characterised in unknown pharmaceutical preparations seized by Belgian authorities, documenting its circulation in unregulated supply chains.
limitations of the evidence
- No published human pharmacokinetic half-life is available for AOD9604 by any route, so duration of exposure is uncharacterised.
- The entire human efficacy and safety database was generated with oral dosing; subcutaneous administration — the dominant real-world route — has never been evaluated in a controlled human trial, so neither its efficacy nor its immunogenicity by that route is known.
- The full efficacy results of the terminated phase 2b programme were described as 'in preparation' in 2014 and have never been published in full, so the failure is documented only through summaries by parties associated with the compound.
- The joint and cartilage claims rest on a single 32-rabbit intra-articular study with no human replication.
documented safety signals
- No treatment-related serious adverse events, no immunogenicity and no glucose or IGF-1 disturbance were detected across six randomised trials in 893 adults — the safety signal here is notably absent, and the failure is one of efficacy.
- The 'GRAS' designation widely cited as a safety endorsement is a self-affirmed food-ingredient determination with no FDA GRAS notice on record, so it carries no independent regulatory review weight.
- Product identity risk: AOD9604 has been documented in unlabelled seized preparations, and the compound is prohibited in sport under WADA S.0, meaning grey-market material has no verified provenance.
identity
| full name | AOD9604 (Tyr-hGH177-191, human growth hormone C-terminal fragment 176-191 analogue) |
| category | Metabolic |
| modality | peptide |
| formula | C78H123N23O23S2 |
| molar mass | 1815.1 g/mol |
| cas | 221231-10-3 |
| sequence | YLRIVQCRSVEGSCGF (Cys7-Cys14 disulfide bridge; N-terminal Tyr substituted for Phe) |
laboratory handling
| storage | Lyophilised peptide is stored at -20 °C, desiccated and protected from light; reconstituted solution is held at 2-8 °C for short-term laboratory use or frozen in single-use aliquots, with freeze-thaw cycles avoided because of the internal disulfide bond. |
| solubility | Soluble in sterile or bacteriostatic water and aqueous buffers; laboratory stocks are commonly prepared in water or dilute acetic acid, with care taken to avoid reducing agents that would cleave the Cys7-Cys14 bridge. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedU.S. Food and Drug Administration / Regulations.gov · 2024 · official
World Anti-Doping Agency · 2013 · official
Journal of Endocrinology and Metabolism · 2013 · peer-reviewed
Journal of Endocrinology and Metabolism · 2014 · peer-reviewed
International Journal of Obesity and Related Metabolic Disorders · 2001 · preclinical
Annals of Clinical and Laboratory Science · 2015 · preclinical
others in Metabolic