AOD-9604 is a modified piece of human growth hormone (the 176–191 region at its tail end) designed in Australia in the 1990s to keep growth hormone’s fat-burning effect while dropping its effects on growth and blood sugar. In obese mice, it worked. It then went through six human trials with about 900 participants, and here the story turns: safety looked indistinguishable from placebo, but in the largest, longest trial, weight loss was not significantly better than placebo, and the developer stopped the obesity program in 2007.
Two details are almost always missing from online summaries. First, every human trial used oral or intravenous AOD-9604, never the injection under the skin that most research vials are sold for. Second, it was at the centre of an Australian sports scandal that made it famous for the wrong reasons. Here is the complete, honest history.
What AOD-9604 is
| Property | Detail |
|---|---|
| Full name | Anti-Obesity Drug 9604 |
| What it is | Synthetic C-terminal fragment of human growth hormone (the 176–191 region) |
| Length | 16 amino acids, with one internal disulfide bond |
| Developed by | Monash University researchers and Metabolic Pharmaceuticals (Melbourne, Australia) |
| Development period | 1990s to 2007 |
| Human trials | Six, about 900 participants, oral and IV only |
| Approved as a drug? | No, anywhere |
The name says what it was for: Metabolic Pharmaceuticals’ compound 9604 was built from day one as an anti-obesity drug, and its whole development history was organized around that single goal.
The idea: separating fat-burning from growth
Growth hormone is a 191-amino-acid protein with many jobs. It promotes growth of bone and tissue (mostly through IGF-1), raises blood sugar by opposing insulin, retains fluid, and breaks down stored fat. People with GH deficiency tend to accumulate abdominal fat, and GH treatment reduces it.
As an obesity drug, though, growth hormone is a poor choice: the IGF-1 increase, the effect on blood sugar and the fluid retention outweigh the fat loss. In the 1990s, Frank Ng and colleagues at Monash University asked whether the fat-burning activity could be isolated in one small part of the molecule. Their work pointed to the C-terminal end, around amino acids 176–191. A synthetic fragment of that region, they reported, could increase fat breakdown in fat tissue without binding the main growth hormone receptor or raising IGF-1.
If that held true in people, it would be the best of both worlds: growth hormone’s effect on fat, without its downsides.
How growth hormone breaks down fat
To understand what AOD-9604 was trying to copy, it helps to know how growth hormone affects fat in the first place. GH acts on fat cells in several ways at once:
- It increases lipolysis, the breakdown of stored triglyceride into fatty acids and glycerol, partly by making fat cells more responsive to adrenaline-type signals.
- It reduces fat storage, by dampening the activity of lipoprotein lipase, the enzyme that pulls fat from the blood into fat cells.
- It shifts fuel use toward fat and away from glucose, which is one reason it raises blood sugar.
Most of these effects run through the growth hormone receptor. The Monash group’s key claim was that the C-terminal fragment produced lipolysis without using that receptor, through a separate, still poorly defined mechanism. Their 2001 work found it didn’t compete for the GH receptor and still worked in mice lacking the beta-3 adrenergic receptor. If true, that would explain why IGF-1 and blood sugar didn’t move. The exact receptor or pathway for AOD-9604 has never been firmly identified, which is one of the open scientific questions about it.
AOD-9604 vs HGH fragment 176–191
These two names are used interchangeably online, and suppliers often list both. In terms of sequence, they are essentially the same peptide. AOD-9604 is usually described as growth hormone residues 177–191 with a tyrosine added at the start, and residue 176 of growth hormone is itself a tyrosine, so the result matches the natural 176–191 stretch.
- “AOD-9604” is the developer’s name for the specific material that went through the trials.
- “HGH fragment 176–191” is a generic description of the same region.
What can genuinely differ between two products with either name is manufacturing quality: purity, whether the disulfide bond between the two cysteines has formed correctly, the salt form, and how much peptide is actually in the vial. Almost all of the published human data is for AOD-9604 as made for the trials.
The animal research
The preclinical case was solid by the standards of the time:
- Ng 2000 (Hormone Research): in obese Zucker rats, 19 days of oral AOD-9604 cut body weight gain by more than half compared with controls and increased fat-tissue lipolysis, without the loss of insulin sensitivity seen with intact growth hormone.
- Heffernan 2001 (International Journal of Obesity): in obese mice, both growth hormone and AOD-9604 reduced body weight gain and increased fat oxidation, but unlike growth hormone, AOD-9604 didn’t raise blood sugar, didn’t bind the growth hormone receptor and didn’t make cells proliferate.
- Heffernan 2001 (Endocrinology): in obese mice, AOD-9604 reduced fat and increased fat breakdown and fat oxidation; it also worked in mice lacking the beta-3 adrenergic receptor, suggesting a mechanism separate from the classic adrenaline pathway.
Importantly, the animal studies also supported the safety goal: the fragment didn’t cause the blood sugar problems associated with full growth hormone.
The six human trials
Between the early 2000s and 2007, Metabolic Pharmaceuticals ran six human studies. A 2013 paper by Stier and colleagues compiled their safety data.
| Trial | Phase | Participants | Route | Duration |
|---|---|---|---|---|
| METAOD001 | I | 15 healthy men | IV, single doses | Single doses |
| METAOD002 | IIa | 23 men with obesity | IV, single doses | Single doses |
| METAOD003 | IIa | 17 men with obesity | Oral, single doses | Single doses |
| METAOD004 | IIa | 36 men with obesity | Oral, daily | 7 days |
| METAOD005 | IIb | 300 adults with obesity | Oral, daily | 12 weeks |
| METAOD006 (OPTIONS) | IIb | About 500 adults with obesity | Oral, daily | 24 weeks |
The first four studies were about safety and how the body handles the compound. The two phase IIb trials were the real tests of whether it caused weight loss.
How the phase IIb trials were designed
The two efficacy trials were reasonably well designed by the standards of mid-2000s obesity research, which is part of why their results carry weight:
- Randomized and double-blind. Neither participants nor investigators knew who was on AOD-9604 or placebo.
- Placebo-controlled. Essential in obesity trials, where people lose some weight simply from being enrolled and monitored.
- Several dose groups. The 12-week trial compared five dose groups with placebo; the 24-week trial focused on lower doses clustered around the one that had looked best.
- Participants with real obesity. BMI of at least 35 in the 12-week trial and 30–45 in the 24-week trial, both men and women.
- Safety monitoring built in. IGF-1, glucose tolerance tests and antibody testing at intervals, which is why the safety data are unusually complete.
The 24-week trial also had a four-week run-in before randomization, a standard step to stabilize participants’ habits before treatment starts. By the time OPTIONS reported, it was a fair test, and it was negative.
What happened in the big trial
The 12-week METAOD005 trial gave the program its moment of optimism: in the lowest dose group, participants lost about 2.8 kg versus 0.8 kg on placebo. Higher doses did not do better, an unusual pattern that by itself should have raised questions.
The 24-week OPTIONS trial was designed to confirm that signal in roughly 500 people over a longer period. It didn’t confirm it. No dose produced weight loss significantly better than placebo. In February 2007, Metabolic Pharmaceuticals announced that the results did not support continuing development for obesity, and the program stopped.
A positive signal in one mid-sized trial that disappears in a larger, longer trial is one of the most common stories in drug development. Small effects in one study are often partly chance. The confirmatory trial exists precisely to check, and in this case it said no.
Why it may have failed in people
There is no single agreed explanation, but several plausible ones:
- Mice aren’t people. Rodent fat metabolism, especially brown fat activity and response to lipolytic signals, differs substantially from humans. Many compounds that reduce fat in mice do nothing in people.
- Lipolysis isn’t weight loss. Breaking down stored fat releases fatty acids, but unless they are burned (and energy intake doesn’t rise to compensate), they can simply be re-stored. Appetite is the dominant lever in human weight control, and AOD-9604 doesn’t appear to act on it.
- Oral delivery. Peptides are largely broken down in the gut. The phase IIb trials used oral tablets and capsules, and it is possible that too little active compound reached fat tissue.
- The effect may be small. Even if a real effect exists, it may be too small to detect against the normal variation in weight within trials.
The route problem: oral trials, injectable vials
This is the detail most often missed. The human trials used intravenous doses (single doses only, in two small studies) and oral tablets and capsules (all the multi-week trials). No published human trial studied AOD-9604 given by injection under the skin.
Most AOD-9604 sold today, including research vials, is lyophilized powder intended for reconstitution. So the human data say little about the material in those vials, in either direction. That’s worth being clear about when you see AOD-9604 “trial results” quoted next to an injectable product.
Safety: the genuinely good news
If AOD-9604’s efficacy story is disappointing, its safety story is unusually reassuring for a research peptide, because it was actually measured in hundreds of people. The 2013 review of all six trials reported:
- A safety and tolerability profile described as indistinguishable from placebo.
- No significant change in IGF-1 across the trials, the key test of whether it behaved like growth hormone.
- No impairment of glucose tolerance on oral glucose tolerance testing.
- No antibodies against AOD-9604 detected in the participants tested.
- No serious adverse events judged definitely related to the drug.
Two caveats: these trials were sponsored by the developer, and they used oral and IV routes, so they don’t describe the risks of injected research material (contamination, sterility, endotoxin), which is Health Canada’s main concern with peptides bought online. More in AOD-9604 side effects.
Cartilage and joint research
After the obesity program ended, AOD-9604 found a second, smaller research life in joints. In a 2015 study in a rabbit model of osteoarthritis, weekly injections of AOD-9604 into the knee (32 rabbits, four groups) reduced cartilage damage scores compared with saline. Combined with hyaluronic acid, it outperformed either treatment alone and shortened the period of lameness.
It is a single animal study, and no human joint trials have been published. It’s still interesting as a research direction, and it’s one reason AOD-9604 is now sometimes discussed alongside BPC-157 rather than only alongside weight-loss compounds. See Peptides for healing and Knee pain treatment in Canada.
The Essendon scandal
AOD-9604 became widely known in 2013 because of the Essendon Football Club supplements program in the Australian Football League. Investigations into substances given to players in 2012 named AOD-9604 among them.
In 2013, WADA issued a statement clarifying that AOD-9604 was prohibited under section S0 of the Prohibited List, because it was not approved for human therapeutic use by any government health authority. The case eventually went to the Court of Arbitration for Sport, which in 2016 banned 34 current and former Essendon players. Those sanctions were for thymosin beta-4, not AOD-9604, but AOD-9604’s reputation never fully separated from the scandal.
GRAS, FDA, Health Canada and WADA
| Body | Status |
|---|---|
| FDA (US) – drug | Not approved. In December 2024, after review by FDA’s compounding advisory committee, it was not added to the list of substances pharmacies may compound, with concerns cited about limited safety data, impurities and immunogenicity. |
| FDA (US) – food | Obtained self-affirmed GRAS (“generally recognized as safe”) status as a food ingredient. This relates to food safety and says nothing about effectiveness. |
| Health Canada | Not an authorized drug. Named among unauthorized injectable peptides seized from a Canadian seller in August 2025. |
| TGA (Australia) | Not an approved medicine. |
| WADA | Prohibited at all times. |
In Canada, AOD-9604 is sold legally only as a research reagent for laboratory use, without health claims. Health Canada’s April 2026 advisory warned against injecting peptides bought online.
AOD-9604 vs GLP-1 drugs vs tesamorelin
| AOD-9604 | Tesamorelin | Semaglutide / tirzepatide | |
|---|---|---|---|
| Mechanism | GH fragment; increases lipolysis | GHRH analogue; restores GH pulses | Incretin agonists; reduce appetite |
| Largest trial | About 500 people, 24 weeks | About 800 people (pooled), 26 weeks | Thousands, 68–72 weeks |
| Main result | No significant weight loss vs placebo | Visceral fat about −15%; little weight change | 15–21% average weight loss |
| Approved? | No | Yes, for HIV abdominal fat | Yes, for obesity |
Full context: Peptides for weight loss and What is tesamorelin?
What AOD-9604 teaches about peptide claims
AOD-9604 is worth understanding even if you never study it, because its history is a template for reading claims about any research peptide:
- Strong mouse data is a starting point, not a result. AOD-9604’s preclinical case was good. It still didn’t work in the confirmatory human trial.
- One positive trial isn’t enough. The 12-week signal didn’t replicate.
- Check the route. Results from oral trials don’t automatically apply to injected material, or vice versa.
- “Safe” and “effective” are different questions. AOD-9604 is a rare case with good human safety data and poor efficacy data.
- Regulatory labels can mislead. GRAS status sounds like an endorsement. It is a food-safety designation.
AOD-9604 timeline
| Year | Milestone |
|---|---|
| 1990s | Monash University researchers identify a lipolytic region at the C-terminal end of growth hormone |
| 2000–2001 | Rat and mouse studies show reduced weight gain and increased fat oxidation without the insulin effects of growth hormone |
| Early 2000s | Phase I and IIa human studies (IV and oral) |
| Mid-2000s | 12-week phase IIb trial in 300 people shows a small effect in the lowest dose group |
| 2007 | 24-week OPTIONS trial finds no dose better than placebo; obesity program stopped |
| 2013 | Essendon investigation; WADA confirms AOD-9604 is prohibited; human safety data published |
| 2015 | Rabbit osteoarthritis study |
| 2024 | Not added to the US compounding list after FDA advisory committee review |
| 2025 | Named among unauthorized peptides seized by Health Canada |
Four myths about AOD-9604
“It’s clinically proven to burn fat.”
It was clinically tested for fat loss, which is more than most research peptides can say, and it failed the largest test. “Proven” refers to the mouse studies.
“It’s FDA-approved.”
It isn’t. The GRAS food-ingredient status is often presented as an approval, but it is not a drug approval and says nothing about weight loss.
“It’s basically HGH without side effects.”
It was designed to have one of growth hormone’s effects, fat breakdown, and none of the others. It has none of growth hormone’s effects on muscle, bone or recovery, so it isn’t a substitute for HGH in any sense.
“The human trials prove injections are safe.”
The human trials used oral and IV forms. They say nothing about the sterility or purity of research vials, which is the risk Health Canada has warned about.
Quality issues in the AOD-9604 market
AOD-9604 is a short, inexpensive peptide, which makes it a common target for low-quality products. Independent testing of grey-market peptides has repeatedly found under-filled vials and degraded material. AOD-9604 also has a specific chemistry point: its two cysteines should be joined by a disulfide bond, and poorly made material can contain the unbonded (reduced) form or linked pairs of molecules. A good certificate of analysis should show:
- A measured molecular mass matching the expected mass of AOD-9604, about 1,815 Da.
- HPLC purity with a chromatogram.
- A batch number that matches the vial.
- The name of the testing laboratory.
More on this in How to spot fake peptides.
For researchers
AOD-9604 remains a reasonable tool for specific laboratory questions:
- Adipocyte lipolysis assays, comparing it with full-length growth hormone and with beta-adrenergic agonists.
- Studies of whether the lipolytic effect is independent of the GH receptor and IGF-1 signalling.
- Chondrocyte and cartilage models, following up the 2015 rabbit study.
- Structure-activity work on the role of the disulfide bond in the fragment’s activity.
TrueLabs supplies AOD-9604 in 5 mg vials from $23, with batch COAs in the COA library. Mass spectrometry identity and HPLC purity are the checks that matter; see How to read a peptide COA.
FAQ
Tap a question to reveal the answer.
What is AOD-9604?
AOD-9604 is a 16-amino-acid synthetic fragment of human growth hormone, from the 176–191 region, developed in Australia as an anti-obesity drug. It was designed to keep growth hormone’s fat-burning effect without its effects on growth, IGF-1 or blood sugar.
Does AOD-9604 work for weight loss?
Not according to the largest human trial. A 12-week trial showed a small benefit at one dose, but a 24-week trial in about 500 people found no dose significantly better than placebo, and development for obesity stopped in 2007.
Is AOD-9604 safe?
Across six human trials with about 900 participants, using oral and intravenous forms, its safety profile was described as indistinguishable from placebo, with no significant changes in IGF-1 or glucose tolerance. Injected use under the skin was not studied in those trials.
Is AOD-9604 the same as HGH fragment 176-191?
In sequence, essentially yes. AOD-9604 is described as growth hormone residues 177–191 with a tyrosine added at the start, which matches the natural 176–191 stretch. “AOD-9604” is the developer’s name for the trial material; the published human data were generated with it.
Is AOD-9604 legal in Canada?
It is not an approved drug in Canada. It is sold legally as a research reagent for laboratory use only. Health Canada named it among unauthorized injectable peptides seized from a seller in 2025.
Is AOD-9604 banned in sport?
Yes. WADA prohibits it at all times. It became widely known through the 2013 Essendon supplements investigation in Australian football.
What does GRAS status for AOD-9604 mean?
GRAS (“generally recognized as safe”) is a US designation for food ingredients. AOD-9604 obtained self-affirmed GRAS status as a food ingredient, which concerns food safety only and does not show that it causes weight loss.
Why do people still use AOD-9604 if it failed?
Mainly because the mouse data and the early 12-week result are widely quoted without the later 24-week result. Some interest has also shifted to its possible effects on cartilage, based on one animal study.
Who developed AOD-9604?
It was developed from research by Frank Ng and colleagues at Monash University in Melbourne, and taken into clinical trials by the Australian company Metabolic Pharmaceuticals.
Related reading
- AOD-9604 side effects
- Peptides for weight loss
- What is tesamorelin?
- How to spot fake peptides
- IGF-1 vs IGF-1 LR3
References
- Ng FM, Sun J, Sharma L, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274–278. PubMed
- Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001;25(10):1442–1449. PubMed
- Heffernan M, et al. 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;142(12):5182–5189. PubMed
- Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J Endocrinol Metab. 2013;3(1-2):7–15. JOFEM
- Kwon DR, Park GY. Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model. Ann Clin Lab Sci. 2015;45(4):426–432. PubMed
- FDA Pharmacy Compounding Advisory Committee, December 4, 2024. FDA
- WADA statement on substance AOD-9604. WADA
- Health Canada. Advisory RA-77807: Unauthorized injectable peptide drugs seized and sold by Canada Peptide. August 1, 2025. Recalls and Safety Alerts
- Health Canada. Think twice before injecting peptides bought online. Public advisory, April 9, 2026. Health Canada
This article summarizes published research and regulatory information for information only and is not medical advice. TrueLabs research compounds are sold for in vitro and laboratory research use only and are not intended for human or veterinary use.