AOD-9604

What AOD-9604 is

AOD-9604 is a lab-made peptide that got as far as Phase 2 clinical trials in people. As of 2026 that is still the furthest it has gone. Most of the human data come from one big obesity program with placebo controls. Metabolic Pharmaceuticals ran it in the middle of the 2000s [10]. The biggest trial in that program did not beat placebo on its main weight-loss measure. The company then stopped developing it for obesity [9]. Later sections cover this in full.

A peptide is a short chain of amino acids, the building blocks of protein. This one has 16. It copies the tail end of human growth hormone (hGH), called the C-terminal fragment, at positions 177 to 191. One extra amino acid, a tyrosine, is added at the front, or N-terminal, end [10], [15].

The idea is more than four decades old:

• Early 1980s. Scientists at Australia’s Monash University made a sequence from this same tail region of hGH. They reported that it kept part of the whole hormone’s antilipogenic activity, meaning it slowed fat storage. It did so by a route separate from the hormone’s usual effects on growth and insulin [1].
• A decade later. A follow-up study confirmed the result with a lab-made 177 to 191 sequence. In tests on isolated fat cells, it matched the antilipogenic activity of whole hGH [2].
• Then in rodents. Obese mice treated long term with the fragment gained less total body weight and had less fat tissue [3].
• AOD-9604 itself. It is the stabilized form of the fragment, with the tyrosine added. Metabolic Pharmaceuticals Ltd developed it. This Australian biotech company’s research program grew straight out of the Monash-linked work [4].

One reported split holds up the whole case for AOD-9604. Two actions of this hGH region are lipolytic, which means releasing stored fat, and anti-adipogenic, which means blocking new fat. In animals, those actions could be separated from two effects of the parent hormone. One is on glucose handling. The other is on the release of IGF-1 (insulin-like growth factor 1) [4], [7], [13]. Suppose that split held up in humans, at a size that matters clinically. Then in principle it would give a metabolic research tool drawn from growth hormone, minus the growth and glucose problems tied to whole hGH.

Two other lines of work exist. Animal research has looked at injecting it into joints to help cartilage [17]. US reviewers have also looked at its safety as a food ingredient, covered under Safety [13].

This guide sums up the peer-reviewed research found on AOD-9604, for education and lab research. It is for use in laboratory research only, not in people.

How much research there is

There are decades of rodent studies and one finished Phase 2 program in people. The key human result was negative.

Question	Answer
How far testing has gone	Phase 2 in people. A big obesity program with placebo controls finished in the middle of the 2000s [10]. Animal and cell work on how it affects fat dates from the early 1980s [1]. A separate line of animal work looks at cartilage [17]. No Phase 3 data were found
Kinds of studies	Phase 2 human trials against placebo. Metabolic studies in obese rodents, some using beta-3-AR knockout animals. One rabbit model of osteoarthritis. A large set of forensic and lab-testing papers written to catch doping and illegal products
Who or what was tested	Obese adults in the Phase 2 trials [10]. For metabolic studies, obese Zucker rats, obese mice and mice with beta-3-AR knocked out [4], [8]. Rabbits in osteoarthritis work [17]. No human trial data from outside the sponsor’s own obesity program were found
Checked by other labs	Several studies agree on the fat-release effect and its tie to beta-3-AR, but they come from one overlapping Monash-linked group [1] to [8]. At Phase 2b scale the human benefit was not repeated, and work on obesity ended [9], [13]. The osteoarthritis result is one rabbit study that nobody else has repeated [17]
Where the work comes from	The early papers on mechanism and metabolism come from a fairly small, overlapping set of Monash-linked scientists and from trials paid for by Metabolic Pharmaceuticals. The testing and anti-doping papers come from anti-doping and forensic labs with no link to that sponsor [11], [14], [15]
Longest study	Phase 2 trials in people lasted from weeks up to a few months [10]. No multi-year human follow-up was found
Approval	No marketing approval from the MHRA, FDA or EMA was found for any medical use. A US food-ingredient status has been reported. It is called GRAS, short for Generally Recognized As Safe. A panel of experts made the finding, and it depends on the supporting safety data being published [10], [13]. WADA’s Prohibited List bans it in sport [11]
Do the results agree	In rodents, yes. The fat-release effect and the beta-3-AR link show up again and again [3], [8]. In people, no. Small early trials reported signs of weight loss. The last and larger trial, at Phase 2b, did not confirm them [13]

How it might work

Nearly all of this section comes from animals and cells. The papers reviewed for this guide include no study of what AOD-9604 binds to in human tissue. Keep that in mind throughout.

A piece of growth hormone that acts on fat

The full hGH protein has 191 amino acids. Its effects on growth and metabolism are usually credited to the growth hormone receptor (GHR), the classical target. When hGH binds GHR, the liver makes IGF-1.

Starting in the early 1980s, scientists reported something different. They made a peptide that matched only the C-terminal region of hGH. That region lies well away from the main surface that binds GHR. The peptide could still block acetyl-CoA carboxylase, a key enzyme for making fat. It did this without going through GHR and IGF-1 [1].

Later, the narrower 177 to 191 sequence did the same in isolated fat cells [2]. Given long term to obese mice, it lowered total weight gain and fat tissue compared with untreated mice [3]. AOD-9604 is the stabilized version of this fragment with a tyrosine added. Later metabolic studies described it [4].

The beta-3 adrenergic receptor

Fat cells carry a switch known as beta-3-AR, the beta-3 adrenergic receptor. The most cited study of how AOD-9604 works used two kinds of mice. Some were ordinary obese mice, called wild-type. Others were bred to lack beta-3-AR, called knockout mice [8].

• Wild-type obese mice. Long-term treatment with whole hGH or with AOD-9604 went along with less weight gain and higher signs of fat release.
• Knockout mice. The response to both compounds was much weaker.

From this the authors proposed that, in this model, its effects on fat depend at least partly on beta-3-AR signaling in fat tissue [8].

A later safety paper summed up research hinting at one way this could happen. In obese animals, beta-3 receptor levels in fat tissue are held down. AOD-9604 may work in part by raising them [13].

Apart from GHR, IGF-1 and glucose

• A different region. AOD-9604 matches a part of hGH that is not the main GHR-binding surface. So scientists think it does not grip the classical GHR the way whole hGH does. They also propose it does not trigger the liver’s IGF-1 release that follows when GHR is switched on. In a cell test, it did not compete for the hGH receptor [7].
• Insulin sensitivity in rats. Obese Zucker rats got AOD-9604 by mouth. They gained less weight and less fat. Long-term whole hGH harms insulin sensitivity in the same rat model, and AOD-9604 did not. This was measured with a euglycemic clamp, a standard test of insulin response [4].
• More fat burned. In other rodent work, whole hGH and an altered C-terminal fragment each raised whole-body fat oxidation, or fat burning, over long-term treatment. The authors described this as a shift toward using fat for fuel, not as something acting directly on insulin signals [7].
• Shape studies. Scientists studied the structure and shape of a ring-shaped (cyclic) peptide related to AOD-9604. Its biological activity fit this fragment-specific, non-GHR way of acting. That backs the wider reason to engineer this hGH region by itself, based on how structure relates to activity [6].

What the beta-3 model leaves open

The knockout mouse data are the strongest single piece of evidence on how AOD-9604 works. The model still has gaps.

• No binding study has pinned down a direct, high-affinity target for AOD-9604 in the papers reviewed for this guide. For some other compounds, scientists have isolated the exact partner the compound binds.
• A later safety paper summed up the beta-3 receptor idea. The same paper plainly said the mechanism is not understood [13].

The beta-3 pathway is the leading proposal in rodent studies. It is not a confirmed, fully described mechanism. Nobody has shown it works the same way in people.

What the studies found

Research tied to AOD-9604 covers more than four decades. It runs from the 1980s finding on the parent fragment to a large Phase 2 obesity program. It also includes animal work on cartilage and many papers on detection, written because the compound is banned in sport.

Early animal and cell studies

• The starting point. A part-sequence from the C-terminal end of hGH blocked acetyl-CoA carboxylase, an enzyme central to making fat. The mechanism differed from the hormone’s classical growth action [1].
• The narrower fragment. The lab-made hGH 177 to 191 sequence showed the same antilipogenic activity in isolated fat cells [2]. Long-term treatment with it lowered total weight gain and fat mass in obese mice [3].
• Zucker rats. In metabolic studies of AOD-9604 itself, obese Zucker rats were dosed by mouth each day. Their weight gain was more than 50% lower than in control rats. The harm to insulin sensitivity linked to long-term whole hGH did not appear [4]. A related fragment, AOD-9401, given by mouth also cut weight gain in obese mice [5].
• Fat burning. Obese mice treated long term burned more fat across the whole body, with whole hGH and with an altered C-terminal fragment [7]. A related study in beta-3-AR knockout mice proposed that these fat effects depend on that receptor [8].
• Structure. Work on a cyclic peptide related to AOD-9604 reported shape and activity results that fit this fragment-specific way of acting [6].

The Phase 2 obesity trials and why the program ended

Metabolic Pharmaceuticals ran a sizable Phase 2 obesity program in the early to mid 2000s. By report, about 900 people took part in all, across six clinical trials. These included pilot studies of dosing into a vein and by mouth, plus two larger efficacy trials against placebo [10].

A later paper’s summary of the program reported weight loss in the trials that came first. The final, larger trial did not show it. That trial paired the study drug with an intensive diet and exercise plan [13].

That last trial, at Phase 2b, did not beat placebo on its main weight-loss measure. Metabolic Pharmaceuticals then ended its obesity program for AOD-9604 [9], [13].

No fact in the human record matters more. The peptide had decades of animal data behind it. It reached a trial large enough to detect an effect, and the effect it was built to show did not appear.

Safety was a separate question, and there the reports were good. Across the trials reviewed, its safety and tolerability could not be told apart from placebo. It had no clinically meaningful bad effect on insulin sensitivity or on how the body handled glucose [10].

Reviews of anti-obesity drugs from around that time put this hGH-fragment approach in context. It was one of the peripheral approaches that target fat tissue. The wider search was for obesity treatments with milder side effects than the earlier generation of drugs [9].

Cartilage and osteoarthritis in animals

A newer line of research has nothing to do with fat. It tests AOD-9604 injected straight into a joint, called intra-articular injection, as a possible aid to cartilage.

Scientists used the enzyme collagenase to cause knee osteoarthritis in rabbits. The rabbits then got weekly joint injections. Some got AOD-9604 alone and some got it with hyaluronic acid. Cartilage regrew better than in rabbits given saline. The two together did better than either one alone [17].

In the papers reviewed for this guide, nobody has published a human trial of AOD-9604 for any joint use, including osteoarthritis and cartilage repair. The rabbit work raises a question worth testing. It is not clinical evidence for any joint use in people.

Detection and anti-doping research

AOD-9604 is on the World Anti-Doping Agency (WADA) Prohibited List. So independent labs have written many papers on how to find it in doping-control samples. This set of papers stands apart from the research on whether it works as a treatment, and in some ways it is larger.

• Does it confuse the hGH test? WADA uses an hGH isoform immunoassay to catch doping with whole growth hormone. Scientists checked whether AOD-9604 would throw off that test. It had no effect on it. This helps anti-doping labs read hGH results from athletes who may also have taken GH-fragment peptides [11].
• A review of methods. One review looked at ways to detect peptide drugs, candidate drugs and structural analogs in sports doping, and it covered AOD-9604. It named it among the peptides derived from growth hormone that need their own detection methods [14].
• A urine test. One team validated a method for finding AOD-9604 and its breakdown products in urine. They described one stable breakdown product. They proposed that it can be detected for longer than the parent peptide [15].
• A 19-peptide screen. A method using liquid chromatography and mass spectrometry was validated to detect 19 peptides used for doping in human urine. It was built for anti-doping labs, and AOD-9604 was one of its targets [16].
• The wider field. A broad review of mass spectrometry in human sports drug testing placed AOD-9604 detection within the general approach used for doping substances related to growth hormone [19].

Illegal products and product quality

Independent forensic and government labs have found AOD-9604 again and again in peptide products that are unregulated and supplied illegally. Their findings are about product quality, not about how the compound acts in the body.

• A seized product in Belgium. Belgian regulators published a case report. They identified and described AOD-9604 in an unknown drug preparation that had been seized on the illegal market. The case shows that a seized product sold under the AOD-9604 name cannot be trusted to match its label unless an independent lab confirms it [12].
• A 25-peptide screen. A wider study looked at illegal peptide biopharmaceuticals that control agencies often come across. It built a general method, using LC-MS/MS, that covers 25 different peptides. That reflects how common unregulated peptide products, including growth hormone fragments, have become in seized-product testing [18].
• Bacteria in injectables. That regulatory research group also published a second case report. It found Bacillus cereus, a bacterium of a kind that breaks down red blood cells (hemolytic), in injectable peptide products supplied illegally. This is a germ risk of the unregulated peptide market as a whole. It is a separate matter from whether any one peptide is safe as a drug [20].

Safety

In trials and in animals

• Human trials. Six human trials from the Metabolic Pharmaceuticals obesity program were reviewed. In them, safety and tolerability were reported as no different from placebo. That included no clinically meaningful bad effect on insulin, on glucose, or on insulin sensitivity measures [10].
• Animal safety tests. A 2014 paper reported gene-damage tests and long-term toxicity tests in rats and monkeys. It found no safety concerns. It also noted that how the compound works is not understood [13].
• Rabbit joints. The osteoarthritis study, which used joint injections in rabbits, reported no new safety signals from AOD-9604, at the joint or body-wide, in that model [17].
• Doping tests. AOD-9604 left WADA’s hGH isoform immunoassay unaffected. That finding bears on how labs read doping-control results, not on the peptide’s safety in the body [11].

Risks from illegal products

The compound’s own trial data are one thing. Products from the unregulated peptide market are another. Independent government labs have repeatedly found quality and contamination risks in them that have nothing to do with how AOD-9604 itself acts.

• A Belgian case report identified AOD-9604 in an unregulated drug preparation that had been seized. It makes the point that a product labeled AOD-9604 may not match its label without independent lab checks [12].
• Wider screening of illegal peptide biopharmaceuticals found the same problem to be common across unregulated peptide products [18].
• A separate case report found hemolytic Bacillus cereus bacteria in injectable peptide products supplied illegally [20].

Together these reports support buying research material only where the supplier gives an independent Certificate of Analysis for each batch.

What is not known

• No Phase 3 trial data have been found. The key obesity trial, at Phase 2b, did not beat placebo on its main measure. The program ended before any Phase 3 work was reported [9], [13].
• The trials lasted weeks to months. The peer-reviewed papers reviewed here do not establish human safety past that.
• No formal drug interaction studies were found.
• The exact molecular mechanism is not fully described. That includes whether beta-3-AR is needed, or is enough by itself, in humans [13].
• For osteoarthritis and cartilage, nothing from a human trial has been published. There is only the one rabbit study [17].

Legal status in the US

• Not approved as a medicine. As of 2026, AOD-9604 is still an experimental compound. No FDA marketing approval was found for any medical use. The same is true of the EMA and the MHRA. Its obesity program ended after the key trial, at Phase 2b, failed to beat placebo.
• Food-ingredient review. A finding by an expert panel that it is a GRAS food ingredient has been reported. It is conditional on publication of the safety data behind it [13].
• Banned in sport. WADA class S2 is named Peptide Hormones, Growth Factors, Related Substances and Mimetics. It takes in growth hormone fragments, releasing factors and related peptides, AOD-9604 among them. Anti-doping labs have built detection methods just for it.
• Research use. It is supplied strictly for use in laboratory research. It is not for use in people or in competition.

Limits of the research

1. The key Phase 2b obesity trial missed its main goal. It was the largest and last trial in the Metabolic Pharmaceuticals obesity program. On weight loss it did not beat placebo, and the AOD-9604 obesity program then ended [9], [13]. All the other human evidence should be read in light of this.
2. No Phase 3 data. Development stopped at Phase 2. No large confirming trial was found in the papers reviewed.
3. The mechanism is not settled. The beta-3-AR pathway is the leading proposal from rodent work [8]. No study of direct receptor binding in human tissue was found. A 2014 paper plainly said the mechanism is not understood [13].
4. Overlapping sponsor and scientists. Much of the early mechanism and human trial work comes from a fairly small, overlapping set of people. They are Monash-linked scientists and research teams paid by Metabolic Pharmaceuticals. No independent repeat of the human benefit findings outside that program was found.
5. Osteoarthritis work is in animals only. The cartilage results rest on one rabbit study. For joint uses of any kind, human trial data were not found [17].
6. Little long-term data. The longest human trials found lasted from weeks up to a few months. Safety and benefit past that point are not described in the peer-reviewed papers reviewed.
7. The unregulated market makes sourcing harder. Independent forensic and regulatory labs keep finding problems in illegal peptide products sold as AOD-9604 or next to it. The problems involve quality, identity and contamination [12], [18], [20]. That is why independent checks of each batch of research material matter.
8. Missing or selective reporting. As with any narrow, sponsor-linked body of peptide research, bias in what gets published and reported cannot be ruled out. The concern is greater for a program that ended after a negative key trial.

AOD-9604 cut fat gain in obese rodents. Its largest human trial did not show weight loss beyond placebo, and no later trial has changed that.

References

Selected peer-reviewed references, each verified against the CrossRef API or PubMed before inclusion. Ordered by date of publication.

1. Bornstein J, Ng FM, Heng D, Wong KP (1983). Metabolic actions of pituitary growth hormone. I. Inhibition of acetyl CoA carboxylase by human growth hormone and a carboxyl terminal part sequence acting through a second messenger. Acta Endocrinologica, 103(4), 479–486. DOI: 10.1530/acta.0.1030479
2. Wu Z, Ng FM (1993). Antilipogenic action of synthetic C-terminal sequence 177–191 of human growth hormone. Biochemistry and Molecular Biology International, 30(1), 187–196. PubMed: PMID 8358331
3. Natera SHA, Jiang WJ, Ng FM (1994). Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177–191 peptide. Biochemistry and Molecular Biology International, 33(5), 1011–1021. PubMed: PMID 7987248
4. Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research, 53(6), 274–278. DOI: 10.1159/000053183
5. Heffernan MA, Jiang WJ, Thorburn AW, Ng FM (2000). Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. American Journal of Physiology-Endocrinology and Metabolism, 279(3), E501–E507. DOI: 10.1152/ajpendo.2000.279.3.E501
6. Ogru E, Wilson JC, Heffernan M, Jiang WJ, Chalmers DK, Libinaki R, Ng F (2000). The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone. Journal of Peptide Research, 56(6), 388–397. DOI: 10.1034/j.1399-3011.2000.00771.x
7. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM (2001). Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity, 25(10), 1442–1449. DOI: 10.1038/sj.ijo.0801740
8. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM (2001). 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, 142(12), 5182–5189. DOI: 10.1210/endo.142.12.8522
9. Valentino MA, Lin JE, Waldman SA (2010). Central and peripheral molecular targets for anti-obesity pharmacotherapy. Clinical Pharmacology & Therapeutics, 87(6), 652–662. DOI: 10.1038/clpt.2010.57
10. Stier H, Vos E, Kenley D (2013). Safety and tolerability of the hexadecapeptide AOD9604 in humans. Journal of Endocrinology and Metabolism, 3(1–2), 7–15. DOI: 10.4021/jem157w
11. Orlovius AK, Thomas A, Schänzer W, Thevis M (2013). AOD-9604 does not influence the WADA hGH isoform immunoassay. Drug Testing and Analysis, 5(11–12), 850–852. DOI: 10.1002/dta.1557
12. Vanhee C, Moens G, Deconinck E, De Beer JO (2014). Identification and characterization of peptide drugs in unknown pharmaceutical preparations seized by the Belgian authorities: case report on AOD9604. Drug Testing and Analysis, 6(9), 964–968. DOI: 10.1002/dta.1687
13. Moré MI, Kenley D (2014). Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health. Journal of Endocrinology and Metabolism, 4(3), 64–77. DOI: 10.14740/jem213w
14. Thevis M, Thomas A, Schänzer W (2014). Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions. Expert Review of Proteomics, 11(6), 663–673. DOI: 10.1586/14789450.2014.965159
15. Cox HD, Smeal SJ, Hughes CM, Cox JE, Eichner D (2015). Detection and in vitro metabolism of AOD9604. Drug Testing and Analysis, 7(1), 31–38. DOI: 10.1002/dta.1715
16. Mazzarino M, Calvaresi V, de la Torre X, Botrè F (2015). Development and validation of a liquid chromatography-mass spectrometry procedure after solid-phase extraction for detection of 19 doping peptides in human urine. Forensic Toxicology, 33(2), 321–337. DOI: 10.1007/s11419-015-0279-4
17. Kwon DR, Park GY (2015). Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model. Annals of Clinical and Laboratory Science, 45(4), 426–432. PubMed: PMID 26275694
18. Vanhee C, Janvier S, Desmedt B, Moens G, Deconinck E, De Beer JO, Courselle P (2015). Analysis of illegal peptide biopharmaceuticals frequently encountered by controlling agencies. Talanta, 142, 1–10. DOI: 10.1016/j.talanta.2015.04.022
19. Schänzer W, Thevis M (2017). Human sports drug testing by mass spectrometry. Mass Spectrometry Reviews, 36(1), 16–46. DOI: 10.1002/mas.21479
20. Janvier S, Wattijn E, Botteldoorn N, De Spiegeleer B, Deconinck E, Vanhee C (2018). Are injectable illegal polypeptide drugs safe? Case report demonstrating the presence of haemolytic Bacillus cereus in 2 illegal peptide drugs. Drug Testing and Analysis, 10(4), 791–795. DOI: 10.1002/dta.2304