Peptides & growth hormone

AOD-9604

Updated · 21 sources · Editorial policy

AOD-9604 (often written AOD9604; “AOD” stands for anti-obesity drug) is a synthetic 16-amino-acid peptide modeled on the tail end of human growth hormone (hGH) (Mendias and Awan, Sports Med 2026). It was developed in Australia, first at Monash University and then by Metabolic Pharmaceuticals, as an oral obesity drug meant to keep growth hormone’s fat-burning effect without its effects on growth, IGF-1 or blood sugar.

The single most important fact: AOD-9604 failed as an obesity drug. In a 24-week phase 2b trial of about 500 adults, weight loss was too small to reach statistical significance, and the developer ended the obesity program in February 2007. It is not approved as a drug in any country. FDA lists it among compounding substances that may pose significant safety risks, and it is banned in sport at all times.

This page summarizes what the sponsor’s trials, the animal studies and regulators report. It is for education only and is not medical advice.

Property Detail
Class Synthetic peptide fragment of human growth hormone (Tyr-hGH 177–191); investigational
Sequence and size YLRIVQCRSVEGSCGF, with one internal disulfide bridge; C₇₈H₁₂₃N₂₃O₂₃S₂, 1815.1 g/mol (PubChem)
Developer Metabolic Pharmaceuticals (Melbourne); obesity program terminated February 2007
Approval Not approved as a drug in any country
Routes tested in humans Intravenous infusion (single doses) and oral capsules or tablets; none of the sponsor’s six trials tested injection under the skin
Doses studied in humans 25–400 µg/kg IV once; 0.25–54 mg/day by mouth for up to 24 weeks
Half-life ≈3 min after IV injection in pigs; ≈4 min in rat plasma in the lab; no human half-life published
Key mechanism fact Does not bind the growth hormone receptor and did not raise IGF-1 in human trials
US compounding status On FDA’s list of bulk substances that may present significant safety risks (nomination withdrawn)
WADA Prohibited at all times (S2.2.3, growth hormone fragments), named explicitly

What it is

Human growth hormone is a 191-amino-acid protein. In the 1990s, researchers at Monash University found that a synthetic copy of its last 15 amino acids (positions 177–191) blocked fat formation in rat fat tissue in the same way as the whole hormone (Wu and Ng, Biochem Mol Biol Int 1993). The group then studied an earlier version called AOD9401 in obese rats (Ng et al., J Mol Endocrinol 2000).

AOD-9604 is the same 177–191 segment with one extra tyrosine added at the front, which the developer says stabilizes the peptide. It is made by solid-phase peptide synthesis (Stier et al., J Endocrinol Metab 2013). The two cysteines form a ring through a disulfide bridge (PubChem).

Peptide Sequence Note
hGH residues 176–191 (natural) FLRIVQCRSVEGSCGF Position 176 in natural hGH is phenylalanine (UniProt P01241)
hGH 177–191 LRIVQCRSVEGSCGF The 15-residue fragment in the original 1993 work
AOD-9604 (Tyr-hGH 177–191) YLRIVQCRSVEGSCGF Tyrosine added in front; 16 residues

Because AOD-9604 has 16 residues in the 176–191 positions, it is often sold or described as “hGH fragment 176–191” (Dominikowski et al., Front Endocrinol 2026). The library has a separate page for HGH Fragment 176-191, and one for full-length HGH. WADA lists “AOD-9604 and hGH 176-191” as separate examples of growth hormone fragments.

Mechanism. In mouse and cell studies, AOD-9604 did not compete with hGH for the growth hormone receptor and did not make receptor-carrying cells multiply, unlike hGH (Heffernan et al., Int J Obes 2001). The developer argued that the fragment cannot activate the receptor because it lacks the second binding site that full hGH needs to pair two receptors (Stier et al., 2013). In obese mice it raised levels of the β3-adrenergic receptor, a fat-cell receptor that drives fat breakdown. Its weight effect disappeared in mice lacking that receptor, yet the authors concluded the receptor was not the direct target (Heffernan et al., Endocrinology 2001). No specific receptor for AOD-9604 has been identified.

Pharmacokinetics

No pharmacokinetic study in humans has been published, and no human half-life has been reported (Dominikowski et al., 2026). The only data come from animal and lab studies done for the developer (Moré and Kenley, J Endocrinol Metab 2014):

Setting Finding
Rat plasma in the lab Half-life ≈4 min; intact peptide undetectable after 56 min
Pigs, 400 µg/kg IV Peak at 2 min; half-life ≈3 min; almost fully cleared by 12 min
Pigs, 2,000 µg/kg by mouth Slower entry into blood, peak at 60 min
Rats, radiolabeled dose Spread to all tissues except the brain and spinal cord, after IV or oral dosing

The peptide is broken down by enzymes that trim amino acids from its front end, one after another. The main breakdown fragments, missing two or three amino acids, kept some anti-fat-formation activity in lab tests. A doping-control lab found one fragment (CRSVEGSCG) that lasted much longer in serum than the parent peptide (Cox et al., Drug Test Anal 2015).

In the pig study, measured oral exposure was higher than IV exposure. The authors themselves said experimental error was the most likely explanation, so this result does not show how well the peptide is absorbed by mouth in people.

Development and regulatory status

  • Obesity program, 2001–2007. Metabolic Pharmaceuticals ran six randomized, placebo-controlled trials with about 900 participants between 2001 and 2006 (Stier et al., 2013). On February 21, 2007, the company announced that the final phase 2b results did not support the drug’s commercial viability, and ended development for obesity (Metabolic half-year report, 2007).
  • Food-ingredient claim. The 2013 safety review states that an expert panel judged AOD9604 “Generally Recognized As Safe” (GRAS) for intended uses in foods (Stier et al., 2013). A GRAS determination is not a drug approval and does not cover injectable products.
  • Not an approved drug. AOD-9604 is not approved by major regulators for any use (Dominikowski et al., 2026).
  • US compounding. FDA lists AOD-9604 among bulk substances nominated for compounding and then withdrawn, on its page of substances that may present significant safety risks. FDA says compounded AOD-9604 “may pose significant risk for immunogenicity” (the risk of triggering an immune reaction) for certain routes, and may have problems with peptide impurities and characterization. FDA says it has no, or only limited, safety information, and that it has identified serious adverse events that may be linked to AOD-9604, although causality is not clear (FDA, updated April 22, 2026).
  • Not part of the 2026 peptide review. FDA’s July 2026 Pharmacy Compounding Advisory Committee meeting reviewed BPC-157, KPV, TB-500, MOTs-C, emideltide, Semax and epitalon. AOD-9604 was not on the agenda (Federal Register notice, docket FDA-2025-N-6895).

What the research shows

Animal studies on body fat

The early work was done by the Monash group that invented the peptide:

  • Obese rats, oral dosing. Obese Zucker rats given 500 µg/kg by mouth daily for 19 days gained 15.8 g, compared with 35.6 g in controls. Fat tissue showed more fat breakdown, and insulin sensitivity was not worsened (Ng et al., Horm Res 2000).
  • Obese mice, continuous infusion. Over 14 days, both hGH and AOD-9604 reduced weight gain in obese mice and increased fat burning. Unlike hGH, AOD-9604 did not raise blood sugar or reduce insulin secretion (Heffernan et al., Int J Obes 2001).
  • Obese mice, injections. Fourteen days of injections into the abdominal cavity reduced body weight and body fat in obese mice (Heffernan et al., Endocrinology 2001).

These were short studies in genetically obese rodents. They do not show that the peptide reduces fat in people, and the human trials below did not confirm a meaningful effect.

Human obesity trials

The six trials were sponsored by Metabolic Pharmaceuticals. We found no full peer-reviewed report of any of the individual trials. What is public comes from a 2013 safety review (two of its three authors worked for the company), company presentations and stock-exchange filings, and later reviews (Stier et al., 2013).

Trial Design and participants Doses Length Reported findings
METAOD001 Phase 1, dose escalation; 15 healthy men 25–400 µg/kg IV, single doses Single doses No significant glucose, glycerol or IGF-1 trends with AOD-9604, hGH or placebo
METAOD002 Phase 2a crossover; 23 men with BMI ≥ 35 25, 50, 100 µg/kg IV, single doses Single doses No change in glucose or IGF-1 vs placebo
METAOD003 Phase 2a crossover; 17 men with BMI ≥ 35 9, 27, 54 mg by mouth, single doses Single doses No change in IGF-1 vs placebo
METAOD004 Phase 2a; 36 men with BMI ≥ 30 9, 27, 54 mg/day by mouth 7 days No change in glucose tolerance or IGF-1
METAOD005 Phase 2b; 300 adults with BMI ≥ 35 1, 5, 10, 20, 30 mg/day by mouth, or placebo 12 weeks 1 mg: 2.6 kg lost vs 0.8 kg on placebo; higher doses did not do better
METAOD006 (“OPTIONS”) Phase 2b; 502 adults with BMI 30–45, with a diet and exercise program 0.25, 0.5, 1 mg/day by mouth, or placebo 24 weeks Weight loss too small to reach statistical significance at 12 or 24 weeks

The 12-week trial. The 2.6 kg vs 0.8 kg figures for 1 mg/day are the numbers most often quoted (Valentino et al., Clin Pharmacol Ther 2010). The company’s own slides show this comparison was a per-protocol analysis of only 34 people on 1 mg and 37 on placebo, that is, people who completed the trial as planned (Metabolic presentations, February 2005). There was no dose-response: people on 10 mg/day lost less weight than those on 1 mg/day (Valentino et al., 2010).

The 24-week trial. To test lower doses, the company ran a larger trial under conditions closer to a phase 3 study. The trial included 536 people in total, of whom 502 were randomized according to the safety review. Weight loss at the 12-week and 24-week endpoints was too low to reach statistical significance. The company stated that AOD-9604 “did not demonstrate the weight loss required to support commercial outcomes” and stopped development for obesity (Metabolic half-year report, 2007).

No controlled human trial has tested AOD-9604 for muscle gain, fat loss in lean or athletic people, or athletic performance.

Joints and cartilage (animal data)

In a study in 32 rabbits with knee osteoarthritis induced by an enzyme injection, weekly injections of 0.25 mg AOD-9604 into the knee improved cartilage scores compared with saline. Combining AOD-9604 with hyaluronic acid worked better than either alone, and shortened the period of limping (Kwon and Park, Ann Clin Lab Sci 2015). No human trial has tested AOD-9604 for joint disease. Claims about joint repair rest mainly on this animal work (Dominikowski et al., 2026).

Side effects and risks

What the trials reported

In the sponsor’s trials, side effects were reported about as often with AOD-9604 as with placebo (Stier et al., 2013):

  • Headache was the most common complaint. In the IV study in obese men, 16 of 23 participants (69.6%) reported mild or moderate headache across the treatment periods, including placebo.
  • Euphoria. In the same study, 5 of 23 participants reported mild or moderate euphoria during AOD-9604 periods, and none during placebo.
  • Digestive effects. At the highest oral dose (54 mg/day for 7 days), headache, diarrhea and flatulence were more frequent.
  • 24-week trial. At least one adverse event occurred in 83.2% of the placebo group and 75.6% of the 0.25 mg group. Serious adverse events occurred in 3.6% of all patients, with a similar distribution across groups.
  • IGF-1 and blood sugar. IGF-1 levels did not differ from placebo in any trial, and oral glucose tolerance tests showed no worsening. In the 24-week trial, IGF-1 differences between groups were not significant (P = 0.51 at 12 weeks; P = 0.76 at 24 weeks).
  • Antibodies. No antibodies against AOD-9604 were found in the participants tested, all of whom took it by mouth.

Cancers in the 12-week trial

Five serious adverse events occurred in the 12-week trial, all in AOD-9604 groups: basal cell carcinoma, squamous cell carcinoma and a lipoma at 20 mg/day, breast cancer at 5 mg/day, and melanoma at 10 mg/day. The investigator judged none related to the drug. The authors noted that none occurred at the highest dose (30 mg/day) and that IGF-1 did not rise (Stier et al., 2013). A 12-week trial is too short to settle questions about cancer risk either way.

Limits of the safety data

  • Sponsor-reported. The human safety data come from a review written with the developer’s staff, not from independent trials.
  • Different routes. The trials used oral doses and single IV infusions. None tested repeated injections under the skin. FDA’s concern about immunogenicity applies to “certain routes of administration” (FDA, 2026).
  • Animal toxicology. In the developer’s studies, oral doses up to 100 mg/kg/day for 6 months in rats and 50 mg/kg/day for 9 months in monkeys caused no toxic effects. Lab tests showed no damage to DNA (Moré and Kenley, 2014). These results do not cover unregulated products.

Product quality

Vials sold as AOD-9604 are not made under drug-approval oversight. AOD-9604 has been found in confiscated vials in the US (Cox et al., 2015) and in unknown preparations seized by Belgian authorities (Vanhee et al., Drug Test Anal 2014). FDA cites possible peptide-related impurities and poor characterization of the active ingredient as concerns for compounded products (FDA, 2026). The dose, purity and identity of gray-market products cannot be assumed to match the label.

  • WADA. AOD-9604 is named in class S2.2.3 of the 2026 Prohibited List (“growth hormone fragments, e.g. AOD-9604 and hGH 176-191”). It is prohibited in and out of competition and is a non-Specified Substance (WADA 2026 Prohibited List).
  • Detection. Anti-doping labs have a urine test with a detection limit of 50 pg/mL, and the stable breakdown fragment may extend how long use can be detected (Cox et al., 2015). AOD-9604 does not affect the WADA hGH isoform immunoassay used to detect growth hormone doping (Orlovius et al., Drug Test Anal 2013).
  • United States. Not an approved drug. FDA’s compounding safety listing is described above.

Key takeaways

  • A modified tail of growth hormone. AOD-9604 is hGH residues 177–191 with an extra tyrosine. It does not bind the growth hormone receptor and did not raise IGF-1 in people.
  • It failed as an obesity drug. A 24-week trial of about 500 adults found no statistically significant weight loss, and the developer ended the program in 2007.
  • The often-quoted 2.6 kg result is weak evidence. It came from a per-protocol comparison of 71 completers in a 12-week trial, with no dose-response, and has not been published as a full peer-reviewed trial report.
  • Generally tolerated in sponsor trials, with gaps. Side effect rates were similar to placebo for oral and single IV doses. Repeated injection under the skin was never tested in these trials.
  • No human evidence for muscle, joints or performance. Cartilage benefits come from a single rabbit study.
  • Flagged by FDA and banned in sport. FDA lists it as a compounding substance that may pose significant safety risks, and WADA prohibits it at all times.

Sources

  1. Wu Z, Ng FM. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochem Mol Biol Int. 1993;30(1):187–196. PubMed.
  2. Ng FM, Jiang WJ, Gianello R, et al. Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. J Mol Endocrinol. 2000;25(3):287–298. PubMed.
  3. 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.
  4. 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.
  5. Heffernan M, Summers RJ, Thorburn A, 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.
  6. Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J Endocrinol Metab. 2013;3(1-2):7–15. doi:10.4021/jem157w. Journal.
  7. Moré MI, Kenley D. Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health. J Endocrinol Metab. 2014;4(3):64–77. doi:10.14740/jem213w. Journal.
  8. Valentino MA, Lin JE, Waldman SA. Central and peripheral molecular targets for antiobesity pharmacotherapy. Clin Pharmacol Ther. 2010;87(6):652–662. PubMed.
  9. Metabolic Pharmaceuticals Limited. US presentations (BIO CEO and Investor Conference and corporate presentation), ASX announcement, February 2005. Internet Archive.
  10. Metabolic Pharmaceuticals Limited. Half-year report for the period ended 31 December 2006 (Appendix 4D), ASX announcement, February 26, 2007. Internet Archive.
  11. 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.
  12. Cox HD, Smeal SJ, Hughes CM, et al. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015;7(1):31–38. PubMed.
  13. Orlovius AK, Thomas A, Schänzer W, et al. AOD-9604 does not influence the WADA hGH isoform immunoassay. Drug Test Anal. 2013;5(11-12):850–852. PubMed.
  14. Vanhee C, Moens G, Deconinck E, et al. Identification and characterization of peptide drugs in unknown pharmaceutical preparations seized by the Belgian authorities: case report on AOD9604. Drug Test Anal. 2014;6(9):964–968. PubMed.
  15. Dominikowski A, Rękoś Z, Olejarz M, et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol (Lausanne). 2026;17:1822475. PubMed.
  16. Mendias CL, Awan TM. Safety and efficacy of approved and unapproved peptide therapies for musculoskeletal injuries and athletic performance. Sports Med. 2026;56(8):1921–1935. PubMed.
  17. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. Updated April 22, 2026. FDA.
  18. Food and Drug Administration. Pharmacy Compounding Advisory Committee; notice of meeting (docket FDA-2025-N-6895). Federal Register. April 16, 2026 (FR Doc 2026-07361). Federal Register.
  19. World Anti-Doping Agency. The 2026 Prohibited List. In effect January 1, 2026. WADA 2026 Prohibited List.
  20. National Center for Biotechnology Information. PubChem compound summary for CID 71300630, AOD-9604. PubChem.
  21. UniProt Consortium. P01241, Somatotropin (Homo sapiens). UniProt.