AOD-9604

Dosing from the Literature

Published for fat loss: oral doses of 0.25–54 mg in six trials, and single IV doses (Stier et al., 2013). Not published: any trial of the under-the-skin injections people use.

The rows give the doses of the developer’s six trials, with each trial’s population, and what community use describes.

What It Is

AOD-9604 is a 16-amino-acid synthetic peptide with the sequence Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (with a disulfide bond between the two cysteine residues), corresponding to residues 177–191 of human growth hormone with an added N-terminal tyrosine (Tyr-hGH 177-191), which stabilizes the peptide (Stier et al., 2013). The fragment was designed to isolate the lipolytic activity of full-length hGH from its growth-promoting and insulin-antagonistic effects, which are mediated by different regions of the 191-amino-acid hGH molecule.

AOD-9604 was developed by Professor Frank Ng and colleagues at Monash University in Melbourne, Australia, during the 1990s, and licensed to Metabolic Pharmaceuticals Ltd (publicly listed on the Australian Securities Exchange). Metabolic advanced the compound through extensive preclinical development and six completed randomized double-blind placebo-controlled clinical trials in 893 people (Stier et al., 2013) before terminating the primary obesity program in 2007 after the Phase 2b OPTIONS study failed to demonstrate statistically significant weight loss at 24 weeks. Subsequent development rights have moved through several licensing arrangements; as of April 2026 AOD-9604 remains investigational.

The compound has been studied via both oral and parenteral (SubQ / intraperitoneal in animals) administration. The original Metabolic Pharmaceuticals clinical program was predominantly oral (tablets), leveraging the relatively robust gastrointestinal stability of the 16-amino-acid fragment with disulfide-bond constraint. Community community use has largely shifted to SubQ administration, following conventional peptide-research practice.

AOD-9604 is not FDA-approved for any indication in the United States and not approved by the EMA, but it has been judged “Generally Recognized As Safe” (GRAS) for intended uses in foods by a panel of experts, a self-affirmed determination (Stier et al., 2013). In Australia, a 2013 TGA warning letter told a business selling AOD 9604 cream for human therapeutic use that such peptide products are therapeutic goods that may not be supplied without entry in the Australian Register of Therapeutic Goods (Therapeutic Goods Administration, 2013).

Mechanism of Action

Most of the mechanism work comes from Frank Ng’s group at Monash and the developer’s trials (Ng et al., 2000; Heffernan et al., 2001; Stier et al., 2013).

• β3-adrenergic receptor expression — In obese mice, AOD-9604 raised β3-adrenergic receptor RNA in fat; in β3-receptor knockout mice, long-term treatment no longer changed weight or lipolysis, though a single dose still raised energy expenditure and fat oxidation, and the authors concluded its lipolysis is not mediated directly through the β3 receptor (Heffernan et al., 2001; PMID 11713213).
• Does NOT bind the hGH receptor — In vitro, AOD-9604 did not compete for the hGH receptor in binding assays and did not make hGH-receptor cells proliferate (Heffernan et al., PMID 11673763). In people, it did not raise IGF-1 or impair glucose tolerance (Stier et al., 2013).
• Increased fat oxidation — In obese mice, 14 days of AOD-9604 by mini-pump raised fat oxidation and plasma glycerol, a marker of fat breakdown, and slowed weight gain (Heffernan et al., 2001; PMID 11673763).
• Anti-lipogenesis — In obese mice given the related peptide AOD-9401 by mouth, fat tissue made less fat and broke more down (Heffernan et al., 2000); the hGH 177-191 region inhibits acetyl-CoA carboxylase in fat and liver cells, as Stier et al. (2013) review.
• Cartilage (secondary interest) — A 2012 workshop presentation put AOD-9604 forward as a candidate therapeutic for osteoarthritis (Wood, 2012); the page cites no published cartilage study.
• Normal glycemic effect — In obese mice it did not raise blood sugar or reduce insulin secretion (Heffernan et al., 2001; PMID 11673763), and in the human trials glucose tolerance did not worsen (Stier et al., 2013).
• Stability — The added N-terminal tyrosine stabilizes the peptide (Stier et al., 2013); the trials’ safety paper reports no human half-life.
• Oral activity — Given by mouth, it slowed weight gain in obese rats (Ng et al., 2000) and mice (Heffernan et al., 2000); its oral bioavailability in people has not been published.

What the Research Shows

AOD-9604's research database is unusually structured around a formal pharmaceutical development program rather than an academic curiosity, producing a cleaner evidence base than most "research peptides":

• Preclinical lipolysis and weight loss in obese mice — Ng FM, Sun J, Sharma L et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Established the lipolytic activity in ob/ob and Zucker rat obesity models without the untoward hGH metabolic effects.
• Heffernan M et al. hGH / AOD9604 lipid metabolism in obese and β3-AR KO mice — In β3-receptor knockout mice, long-term AOD-9604 no longer changed weight or lipolysis, but a single dose still raised energy expenditure and fat oxidation; the authors concluded its lipolysis is not mediated directly through the β3 receptor (Heffernan et al., 2001; PMID 11713213).
• PMID 11673763 — Heffernan MA 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 (a piece from the tail end of the peptide chain) — Both hGH and AOD-9604 reduced body-weight gain in obese mice, with increased in-vivo fat oxidation and elevated plasma glycerol; AOD-9604 did NOT induce hyperglycemia or reduce insulin secretion — the defining divergence from full-length hGH. AOD-9604 does not interact with the hGH receptor, confirming the "fragment pro-hormone" hypothesis.
• Phase 1 and 2a safety studies — Single IV doses up to 400 µg/kg and oral doses of 9–54 mg, single or daily for a week, in 91 men: side effects no different from placebo, and no change in glucose or IGF-1 (Stier et al., 2013).
• 12-week Phase 2b (METAOD005) — 300 obese adults on 1, 5, 10, 20 or 30 mg a day by mouth, or placebo, 50 per group; side effects were similar across groups, and glucose tolerance did not change significantly (Stier et al., 2013). The developer reported 2.6 kg lost on 1 mg against 0.8 kg on placebo; the weight results were not published in a journal.
• Phase 2b OPTIONS study (METAOD006) — 502 obese adults randomized (534 enrolled) to 0.25, 0.5 or 1 mg a day or placebo for 24 weeks (Stier et al., 2013; ANZCTR ACTRN12605000067673). The developer reported that it failed its weight-loss endpoint and ended the obesity program in 2007; no results were posted or published.
• Cosmetic-ingredient development — AOD-9604 is marketed in topical skincare formulations in Australia and several other jurisdictions as a cosmetic anti-aging ingredient. Evidence base for topical skin applications is minimal and largely consists of manufacturer in-vivo consumer-perception studies rather than published peer-reviewed trials.
• Safety review (Stier et al., J Endocrinol Metab 2013) — The six randomized, placebo-controlled trials (893 people, oral and IV) found side effects indistinguishable from placebo, no rise in IGF-1, no worsening of glucose tolerance and no antibodies to the peptide; two of the three authors worked for the developer.
• Comparison to GLP-1 drugs — Liraglutide 3.0 mg took off 8.4 kg in 56 weeks, against 2.8 kg on placebo (Pi-Sunyer et al., 2015); no AOD-9604 trial has published a weight result.

Human Data

AOD-9604 has one of the more extensive controlled human databases of any research peptide on this site — a direct consequence of having completed a formal pharmaceutical development program:

• Six completed RCTs, 893 people — Phase 1 and Phase 2 studies, IV and oral, from single doses to 24 weeks (Stier et al., 2013).
• Phase 1 and 2a safety studies — Single IV doses of 25–400 µg/kg in 15 healthy men and 25–100 µg/kg in 23 obese men, and oral doses of 9–54 mg, single or daily for 7 days, in 53 obese men (Stier et al., 2013).
• 12-week Phase 2b — 300 obese adults on 1–30 mg a day (Stier et al., 2013); the developer reported 2.6 kg lost on 1 mg against 0.8 kg on placebo.
• Phase 2b OPTIONS study (2007) — 502 obese adults on 0.25–1 mg a day or placebo for 24 weeks (Stier et al., 2013). The developer reported that it failed its primary endpoint and ended development.
• Osteoarthritis — No human osteoarthritis trial of AOD-9604 is registered on ClinicalTrials.gov or indexed in PubMed (searched October 11, 2026).
• Cosmetic / topical skin studies — Manufacturer consumer-perception in-vivo studies for cosmetic applications; not peer-reviewed dermatology research.
• FDA PCAC "Saving AOD9604" submission (Dec 2024) — Edwin Lee MD submitted a presentation to the FDA Pharmacy Compounding Advisory Committee arguing for AOD9604 compounding eligibility, citing the safety database and mechanistic differentiation from full hGH. The committee voted 12 to 0 against adding AOD-9604 to the 503A bulks list (FDA’s final summary minutes, December 4, 2024).
• No published data for SubQ community doses — The trials gave it by mouth (0.25–54 mg) or by IV infusion (Stier et al., 2013); none tested the under-the-skin injections at 250–500 mcg a day that community use describes.

Reconstitution & Storage

AOD-9604 has no approved label, so no official storage or handling instructions exist. Research-chemical sellers list it as freeze-dried powder in 2 mg and 5 mg vials. In its trials it was given as capsules or tablets, and the IV doses were made up from freeze-dried powder with sterile water (Stier et al., 2013).

• Reconstitution arithmetic — For a 2 mg vial, 1 mL of bacteriostatic water gives 2,000 mcg/mL; 500 mcg, the top of the community range, is then 0.25 mL (25 units on a U-100 insulin syringe).

→ Calculator — vial-to-syringe math

Side Effects & Risks

The safety findings below come from the developer’s six trials, summarized by Stier et al. (2013), two of whose three authors worked for the developer.

• Overall tolerability — Across the six trials, the authors found side effects indistinguishable from placebo, with no treatment-related withdrawals or serious events, at oral doses up to 54 mg and IV doses up to 400 µg/kg (Stier et al., 2013). In the 12-week trial, five people on AOD-9604 had serious adverse events, four of them cancers (basal and squamous cell skin cancers, breast cancer, melanoma) and one a lipoma, all judged unrelated by the investigator (Stier et al., 2013).
• Headache and gastrointestinal effects — The most common adverse events were headache and diarrhea, about as common on placebo; at 54 mg a day for a week, headaches, diarrhea and flatulence were more frequent, and after single IV doses 5 of 23 men reported mild euphoria (Stier et al., 2013).
• No glucose intolerance — Unlike full hGH, AOD-9604 did not impair glucose tolerance in the trials (Stier et al., 2013).
• No IGF-1 elevation — AOD-9604 does not act through the hGH receptor (Heffernan et al., 2001; PMID 11673763), and IGF-1 did not change in the 12- and 24-week trials (Stier et al., 2013).
• No hGH-like side effects reported — The trials’ authors report none of the adverse effects associated with full-length growth hormone (Stier et al., 2013).
• Pregnancy and lactation — Not studied: the 12-week trial enrolled only women who could not become pregnant (Stier et al., 2013).
• Pediatric — Not studied: all six trials enrolled adults (Stier et al., 2013).
• Sourcing / purity — Outside the trials, it is sold only as a research chemical, unregulated for quality.
• WADA — AOD-9604 is prohibited at all times: the 2026 Prohibited List names it under S2.2.3, among growth hormone fragments (“AOD-9604 and hGH 176-191”) (WADA Prohibited List 2026).

Bloodwork & Monitoring

No label or guideline sets monitoring for AOD-9604. Its trials checked vital signs, ECGs, blood counts, blood chemistry and lipids, and in the longer trials IGF-1, oral glucose tolerance and antibodies to the peptide (Stier et al., 2013).

Commonly Stacked With

The pairings below are what community use describes; no trial has tested any of them.

Stacking this? Read the receipt →

→ Calculator — vial-to-syringe math

Legal Status

Related Compounds

What AOD-9604 users end up weighing against it:

Next Steps

References

1. Ng FM, Sun J, Sharma L, Libinaki R, Jiang WJ, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-278. PMID: 11146367. (Foundational mechanistic characterization.)
2. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. 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. PMID: 11713213. (β3-AR knockout dependence.)
3. Heffernan MA, Jiang WJ, Thorburn AW, Ng FM. Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. Am J Physiol Endocrinol Metab. 2000;279(3):E501-E507. PMID: 10950816.
4. Ng FM, Sun J, Adamafio NA, Spiteri J, Farag FM, Belot J, Morris HR. Stability and solution properties of a synthetic C-terminal lipolytic domain of human growth hormone (AOD9604). Proc Aust Soc Med Res. 1999;32:97-105.
5. Heffernan MA, Thorburn AW, Fam B, Summers R, 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. PMID: 11673763. (Both hGH and AOD-9604 reduce body weight; AOD does not interact with hGH receptor or produce glucose intolerance.)
6. Metabolic Pharmaceuticals Ltd. Phase 2 OBESITY clinical trial results: AOD9604 12-week dose-ranging study in obese adults (1, 5, 10, 20 or 30 mg/day, against placebo). 2004-2005. (Positive Phase 2 signal at 1 mg/day: 2.6 kg weight loss vs 0.8 kg placebo.)
7. Metabolic Pharmaceuticals Ltd. Phase 2b OPTIONS clinical trial results: AOD9604 24-week randomized placebo-controlled trial: 536 subjects enrolled, by the developer’s count; Stier et al. (2013) report 534 enrolled and 502 randomized. 2007. (Failed primary endpoint. Publicly disclosed in biotech press; led to obesity program termination.)
8. The effect of AOD9604 on weight loss in obese adults: Results of a randomized, double-blind, placebo-controlled, multicenter study (referenced in Chugh 2012 review).
9. Chugh PK, Sharma S. Recent advances in the pathophysiology and pharmacological treatment of obesity. J Clin Pharm Ther. 2012;37(5):525-535. DOI: 10.1111/j.1365-2710.2012.01347.x. (Places AOD-9604 in obesity-pharmacotherapy context.)
10. Kim GW, Lin JE, Blomain ES, Waldman SA. Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther. 2014;95(1):53-66. PMID: 24105257. (Obesity pharmacotherapy review discussing AOD-9604's Phase 2b failure.)
11. Misra M. Obesity Pharmacotherapy: Current Perspectives and Future Directions. Curr Cardiol Rev. 2013;9(1):33-54. PMC: PMC3584306. (Review describing AOD-9604 Phase 2 results and 2007 program termination.)
12. Safety review in the Journal of Obesity & Food Metabolism aggregating six RCTs of AOD-9604 (>900 subjects). (Comprehensive safety database summary.)
13. Wood A. AOD-9604 as a potential candidate therapeutic for osteoarthritis. Cartilage research workshop presentation 2012. (Post-obesity-program pivot toward cartilage repair.)
14. Lee E. "Saving AOD9604" — FDA Pharmacy Compounding Advisory Committee meeting submission, December 4, 2024. (Advocacy presentation for AOD9604 compounding reclassification.)
15. US FDA. Bulk Drug Substances That Raise Significant Safety Risks (Category 2). fda.gov. (AOD-9604 appears in the page's table of substances nominated but withdrawn.)
16. Therapeutic Goods Administration (Australia). Documents released under freedom of information request FOI 1103: warning letter RCU 14320, “Advertising and Supply of unapproved & unevaluated therapeutic goods generally known as ‘Peptides’”, February 7, 2013 (names AOD 9604 cream). tga.gov.au/sites/default/files/foi-1103-1819-01.pdf. Archived copy read October 11, 2026.
17. ClinicalTrials.gov. Metabolic Pharmaceuticals AOD9604 Phase 2 / Phase 2b obesity trials registration and results. clinicaltrials.gov. (Trial documentation.)
18. WADA. The 2026 Prohibited List. World Anti-Doping Agency. wada-ama.org. (S2.2.3: “growth hormone fragments, e.g. AOD-9604 and hGH 176-191”.)
19. Greenway FL, de Jonge L, Blanchard D, Frisard M, Smith SR. Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition. Obes Res. 2004;12(7):1152-1157. PMID: 15292480. (Background context for lipolytic obesity-supplement landscape that AOD-9604 competes within.)
20. 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.
21. Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22. PMID: 26132939. (Comparator: GLP-1 agonist obesity therapeutic evidence — the modern standard AOD-9604 fails to meet.)
22. FDA. Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, December 4, 2024. https://www.fda.gov/media/185642/download. Read October 18, 2026.

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