What it is
AOD-9604 is a lab-made piece of human growth hormone. Growth hormone is a large protein, and one small section at its tail end was thought to carry its fat-burning effect without its effects on growth or blood sugar. AOD-9604 copies 15 amino acids from that tail and adds one more at the front, making 16 in total.
It was developed in Australia in the late 1990s and 2000s as a possible pill for obesity. In mice it reduced body fat. In people, the company’s largest trial found no meaningful weight loss compared with placebo, and development for obesity stopped in 2007. It is not an approved medicine anywhere. It is not the same molecule as the peptide sold as “HGH fragment 176-191”, which differs by its first amino acid.
AOD-9604 is Tyr-hGH(177–191): residues 177–191 of human growth hormone with an added N-terminal tyrosine (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe), cyclised by a disulfide bond between Cys7 and Cys14 (C78H123N23O23S2, 1815.1 g/mol, CAS 221231-10-3).
The rationale was that lipolytic activity of hGH resides in its C-terminus, separable from receptor-mediated growth-promoting and diabetogenic effects. In obese rodents AOD-9604 reduced lipogenesis and increased lipolysis and fat oxidation, without the hyperglycaemia or insulin resistance seen with hGH. Heffernan et al. (2001) found that it increased β3-adrenergic receptor expression in adipose tissue, but that its chronic effects were absent in β3-AR knockout mice while acute fat oxidation persisted, so the mechanism was not resolved. No receptor has been identified, and the sponsor’s trials reported no change in IGF-1.
Pharmacokinetics are known only from animals: in pigs, intravenous AOD-9604 had a half-life of about 3 minutes, while oral dosing at 2 mg/kg produced a plasma peak at about 60 minutes (Moré and Kenley, 2014). Human pharmacokinetic data have not been published.
Who made it and when
The peptide came from Frank Ng’s laboratory at Monash University in Melbourne, which had been studying the fat-burning part of growth hormone. A Melbourne company, Metabolic Pharmaceuticals, developed and patented it in the late 1990s and ran a series of human trials in the 2000s, mostly with oral tablets.
After its main obesity trial failed in 2007, the company, later part of Calzada Ltd, tried other routes to market. In 2012 it announced that a panel of experts it had hired had judged AOD-9604 “generally recognised as safe” for use in food. That is a company-commissioned opinion, not an FDA decision. The company also patented uses in osteoarthritis and cartilage repair.
Ng and colleagues at Monash reported the lipolytic and antilipogenic actions of synthetic hGH C-terminal fragments: AOD-9401 (Am J Physiol Endocrinol Metab 2000) and AOD-9604 (Horm Res 2000, in obese Zucker rats; Int J Obes and Endocrinology 2001, in mice). Metabolic Pharmaceuticals ran six randomised, double-blind, placebo-controlled studies (METAOD001–006), summarised by company-affiliated authors in Stier et al. (2013).
On 2012-06-25 Calzada announced a “conditional self-affirmed GRAS” determination by an expert panel it convened, for food use at up to 1 mg per person per day, conditional on publishing its safety data (published 2013–2014). A self-affirmed GRAS conclusion is the company’s own determination and is not reviewed or affirmed by FDA; FDA’s 2024 evaluation, which searched the GRAS Notice Inventory, did not cite any FDA GRAS notice for AOD-9604. Metabolic Pharmaceuticals holds US 10,111,933 and US 10,758,593, both titled “Use of growth hormone fragments”, with 2011 priority, covering osteoarthritis, cartilage and connective-tissue uses. Published cartilage data come from a rabbit osteoarthritis model (Kwon and Park, 2015).
What the data say
In obese mice and rats, AOD-9604 reduced weight gain and body fat without raising blood sugar, which was the original hope.
In people, the results did not hold up. Early small studies found signs of increased fat breakdown in the blood but no statistically clear weight loss. A 12-week study of 300 people reported slightly faster weight loss on the lowest dose, but only a short conference summary was ever published. The largest trial, in 536 people over 24 weeks with diet and exercise, found no significant difference from placebo, and the company stopped. The FDA found no human study testing it as an injection under the skin or as a skin cream, the forms proposed for compounding, and concluded in 2024 that evidence to support its effectiveness for obesity is lacking.
Animal data: in obese Zucker rats, oral AOD-9604 500 µg/kg daily for 19 days reduced body weight gain by over 50% (Ng et al., Horm Res 2000). In ob/ob mice, 14 days by osmotic minipump or intraperitoneal injection reduced weight gain by about 5–10%, with increased fat oxidation and plasma glycerol and no change in glucose or insulin (Heffernan et al., 2001).
Human data (all oral or intravenous, as summarised in FDA’s 2024 review): METAOD002 (n=23, single IV doses 25–100 µg/kg) raised non-esterified fatty acids without significant weight loss. METAOD003 (n=16–17, oral 9–54 mg) and METAOD004 (n=36, oral 9–54 mg for 7 days) showed no significant weight loss. METAOD005 (n=300, oral 1–30 mg daily for 12 weeks) was reported only as an abstract: 0.22 kg per week at 1 mg versus 0.07 kg per week on placebo. OPTIONS/METAOD006 (536 enrolled, 502 randomised, oral 0.25–1 mg daily for 24 weeks) was powered to detect a 1.8 kg difference and did not reach significance at 12 or 24 weeks.
FDA concluded that in most of the studies it reviewed AOD-9604 did not reduce weight more than placebo, and found no human data for the subcutaneous or transdermal routes proposed for compounding.
Regulatory picture
Three separate facts. Approval: no medicine containing AOD-9604 is approved by the FDA or any other regulator. Compounding: in September 2023 the FDA put AOD-9604 on its “Category 2” list of ingredients that raise safety concerns for pharmacy compounding. The pharmacies that nominated it withdrew their nominations, so in September 2024 the FDA took it off that list, but reviewed it anyway. In December 2024 the FDA’s compounding advisory committee voted 12 to 0 against adding it to the list of ingredients pharmacies may use. Food use: the 2012 “safe for food” claim was the company’s own, not an FDA finding. Sport: it is banned by the World Anti-Doping Agency, and an Australian Crime Commission report named it among peptides supplied to athletes.
Approval: none. Development for obesity was terminated on 2007-02-21, and no IND-stage programme has been verified since. No study is registered on ClinicalTrials.gov.
Compounding: AOD-9604 entered 503A Category 2 on 2023-09-29 and was removed on 2024-09-27 after the nominations (Wells Pharmacy and the International Peptide Society) were withdrawn. FDA evaluated AOD-9604 (free base) and AOD-9604 acetate on its own initiative for obesity and proposed not adding them, citing poor physicochemical characterisation, missing endotoxin data for injectables, immunogenicity concerns, lack of efficacy and limited safety data. On 2024-12-04 the Pharmacy Compounding Advisory Committee voted 0 yes, 12 no, 0 abstain. It is not on the 503A bulks list in 21 CFR 216.23. No final FDA rule on AOD-9604 was found, so this article records compounding status as unknown.
Food: the 2012 GRAS determination was self-affirmed by a company-convened panel; no FDA review of it was found.
Sport and Australia: FDA’s review notes that WADA lists AOD-9604 under S2 (peptide hormones, growth factors and related substances), that the Australian Crime Commission reported its supply to athletes, and that Australia’s Advisory Committee on Medicines Scheduling recommended adding it to the Poisons Standard as a performance- and image-enhancing drug.
