AOD-9604: What the Obesity Trials Showed

AOD-9604 is a 16-amino-acid synthetic peptide based on residues 177 to 191 of human growth hormone, developed by the Australian company Metabolic Pharmaceuticals as an obesity drug, and its largest trial did not show significant weight loss compared with placebo. The company ended development for obesity in February 2007. It is not FDA-approved, an FDA advisory committee voted 0 to 12 against allowing it in compounding in 2024, and the "GRAS" status often quoted for it was a company-commissioned food-ingredient determination, not an FDA approval or review.

What remains is a set of mouse studies, a few small human trials described mostly in summaries, and one failed phase 2b trial.

What it is

Growth hormone is a 191-amino-acid protein. AOD-9604 is a synthetic version of a region near its far end, the C-terminal domain: residues 177 to 191, with an added tyrosine, giving 16 amino acids, according to the FDA's 2024 review. Metabolic Pharmaceuticals developed and patented it in the late 1990s.

The idea was to keep growth hormone's effects on fat while leaving its other effects behind. The FDA's review summarizes rodent and cell studies reporting that AOD-9604 reduced fat and body weight in obese rodents, did not change blood glucose or insulin in rodents, and did not bind or activate the growth hormone receptor in cells. It also concludes that the molecular target and mechanism behind those effects remain unknown. Whether any of it held in people was the question the trials were meant to answer.

The animal work

Heffernan and colleagues (Endocrinology, 2001) treated obese mice with human growth hormone or AOD-9604 for 14 days and reported reduced body weight and body fat with both, along with increased expression of the beta-3 adrenergic receptor, a receptor on fat cells involved in fat breakdown. In mice lacking that receptor, long-term treatment did not produce the same weight change, although a short experiment still showed increased energy expenditure and fat burning. The authors concluded that the fat-related effects were not mediated directly through that receptor.

An earlier study (Natera and colleagues, Biochemistry and Molecular Biology International, 1994) reported less weight gain and less fat tissue in obese mice treated with the synthetic 177 to 191 fragment. Both are mouse findings.

The human trials

The published human record is thin, and much of it exists only as summaries. The FDA's December 2024 briefing document gathered it.

Early studies. A 2004 review (Wilding) briefly described three small double-blind studies in adults with obesity, of 23, 16 and 36 participants, lasting one to four weeks. In the FDA's reading, none showed statistically significant weight loss compared with placebo, and the publication gave limited detail on methods and results.

A 12-week study of 300 adults. A 2005 meeting abstract (Herd and colleagues) reported greater weight loss than placebo across treatment groups, with differences the FDA described as small and of unclear meaning. The FDA said it could not locate a full publication.

The OPTIONS phase 2b trial. This was the decisive test: a randomized, double-blind, placebo-controlled trial that enrolled 536 adults with obesity, of whom 502 were randomized, given AOD-9604 or placebo by mouth for 24 weeks alongside a supervised diet and exercise program. According to the company's filing summarized by the FDA, weight loss compared with placebo at 12 and 24 weeks was too small to reach statistical significance. On February 21, 2007 Metabolic Pharmaceuticals announced that the results did not support the drug's commercial viability for obesity and that development for that condition was terminated. The FDA noted that the trial does not appear to have been published, and found no AOD-9604 studies on ClinicalTrials.gov.

Safety. A 2013 paper by authors employed by or consulting for the developer (Stier and colleagues, Journal of Endocrinology and Metabolism) summarized safety data from six randomized trials. The FDA reviewed it and noted that the six trials were funded by the company. The agency's own conclusion was that clinical safety information is limited, that it found no human data for the routes proposed in the compounding nominations, and that serious adverse events reported in the oral studies included diarrhea, chest tightness and various cancers. The FDA's safety summary states that causality is not clear.

The GRAS history

AOD-9604 is often described online as having "GRAS" status. The record shows something narrower than that phrase suggests.

On June 25, 2012, Metabolic Pharmaceuticals' parent company, Calzada, announced to the Australian Securities Exchange that an expert scientific panel it had engaged, through the consultancy GRAS Associates, had made a conditional determination that AOD-9604 was "generally recognized as safe" as a food ingredient. The announcement said full status was conditional on publishing the company's safety studies in a peer-reviewed journal, and the company's chief executive called it "a self-affirmed conditional GRAS status." In August 2014 the trade publication Lab Online reported, citing the company, that the peptide had been designated GRAS in the US.

Three points follow from that record. First, GRAS is a food-law concept about ingredients in food under their intended conditions of use. It is not a drug approval, and it says nothing about a product sold as a drug. Second, the determination was the company's, made by experts it engaged. The FDA's GRAS notification program allows any person to notify the agency of such a conclusion, and the agency then responds. Third, when we searched the FDA's GRAS Notice Inventory on October 22, 2026, we found no notice for AOD-9604, so we found no record that the FDA reviewed this determination.

Regulatory status

FDA approval. None, for any use.

Compounding. AOD-9604 was nominated for the 503A bulks list for obesity and placed in Category 2, the category for substances that may present significant safety risks. Its nominations were withdrawn, and the FDA evaluated it on its own initiative. At the Pharmacy Compounding Advisory Committee meeting on December 4, 2024, the committee voted 0 to 12 against adding it. The FDA's safety summary lists AOD-9604 among withdrawn substances, noting limited safety information and serious adverse events that may be associated with it.

Sport. The World Anti-Doping Agency's 2026 Prohibited List bans growth hormone fragments at all times under section S2.2.3 and names AOD-9604 as an example.

For how AOD-9604 sits against the compounds in this field with large human trials, see our review of the metabolic class, and for the wider regulatory picture, our guide to which peptides are FDA-approved.

Frequently asked questions

What is AOD-9604?

A synthetic 16-amino-acid peptide based on the C-terminal region of human growth hormone, residues 177 to 191 plus an added tyrosine, developed in Australia as an obesity drug.

Did AOD-9604 work in clinical trials?

Its phase 2b trial in 502 randomized adults did not show weight loss significantly greater than placebo, and the developer stopped obesity development in 2007.

Is AOD-9604 FDA-approved?

No. An FDA advisory committee also voted 0 to 12 against adding it to the compounding bulks list in December 2024.

Does AOD-9604 have GRAS status from the FDA?

Its developer announced a GRAS determination made by experts it engaged. We found no GRAS notice for it in the FDA's inventory, and GRAS concerns food ingredients, not drugs.

Is AOD-9604 banned in sport?

Yes. WADA names it as a prohibited growth hormone fragment under S2.

Sources:

No compound discussed in this review is FDA-approved. Nothing above is dosing guidance or a treatment claim. Research use only.

For research use only · Not for human or veterinary use · No research compound discussed here is FDA-approved for any indication