Last reviewed May 22, 2026·Editorial Board
AOD-9604
Also known as AOD9604, HGH fragment 176-191, HGH frag 177-191, Lipolytic GH fragment
AOD-9604 is a 16-amino-acid synthetic peptide based on the C-terminal lipolytic domain of human growth hormone (residues 177–191) with an added N-terminal tyrosine. It was developed by Metabolic Pharmaceuticals (Australia) as a candidate obesity drug and progressed through six human clinical trials before development was halted in 2007 when the pivotal Phase 2b trial failed its primary efficacy endpoint.[1]
What AOD-9604 is
AOD-9604 ("Anti-Obesity Drug 9604") is the lipolytic C-terminal fragment of human growth hormone (residues 177 through 191) with an additional tyrosine appended to the N-terminus for synthesis and identification purposes. The molecule was first characterized at Monash University by F.M. Ng and colleagues as the minimal sequence of GH carrying the lipolytic and antilipogenic activity of the full hormone, in animal models, without the metabolic effects of full GH (insulin resistance, IGF-1 elevation).[2]
The biological argument was attractive: dissociate the desired lipolytic action of GH from the undesired metabolic effects. Metabolic Pharmaceuticals licensed the technology and brought AOD-9604 into a methodical six-trial human development program targeting obesity.
Mechanism of action
In animal models, AOD-9604 was reported to:
- Stimulate lipolysis in adipocytes via a mechanism distinct from beta-3 adrenergic receptors (the original drug rationale was a non-adrenergic lipolysis pathway)[2]
- Inhibit lipogenesis
- Not engage the somatogenic GH receptor at clinically achievable doses, and therefore not raise IGF-1 or affect glucose tolerance[1]
The β3-adrenergic receptor knockout mouse work (Heffernan 2001) was the key pre-clinical evidence that AOD-9604's lipolytic effect was mechanistically distinct from β3-adrenergic agonist obesity drugs.
The clinical translation, however, did not match the pre-clinical signal — see below.
Human evidence
The AOD-9604 human program is one of the more transparent failures in the peptide therapeutics field, with safety data published and a pooled summary of all six trials available.
The pooled animal data (Heffernan 2001 and related) showed clean lipolytic and antilipogenic effects. The pooled human data showed clean safety but no efficacy at the primary endpoint of weight loss. This is the central editorial point about AOD-9604: it has more human safety data than most peptides marketed today, and it has clearer evidence of efficacy failure than most peptides marketed today.
Marketed claims vs. published evidence
The dataset supports a narrow set of claims: AOD-9604 is well-tolerated in humans, does not produce GH-typical metabolic disturbances, and showed lipolytic effect in animal models. The dataset does not support claims of clinically meaningful human weight loss; the largest human trial designed to test that question returned a negative result.
Regulatory status
- No regulatory approval anywhere. AOD-9604 has not been approved as a drug by the FDA, EMA, TGA (Australia), or any other major regulatory authority.[1]
- 2023 FDA Category 2. Placed on the FDA Category 2 list of bulk substances not eligible for 503A compounding, halting US compounding pharmacy preparation.[3]
- April 23, 2026 reclassification to Category 1. Returned to compoundable status alongside BPC-157, TB-500, Thymosin Alpha-1, and others.[4] Final PCAC review scheduled for July 23–24, 2026.
WADA status: AOD-9604 is not explicitly listed in WADA S2 by name, but as a fragment of human growth hormone it has been considered prohibited under broader peptide-hormone language in some interpretations.[5] Competing athletes should consult their sport-specific anti-doping authority and not assume permissibility from absence of explicit listing.
Safety considerations
The 6-trial pooled safety dataset (~900 participants) is one of the cleaner human safety records in the peptide therapeutics literature. Reported adverse events were indistinguishable from placebo. There were no significant changes in IGF-1, no impact on glucose homeostasis, no anti-AOD-9604 antibodies detected, and none of the metabolic disturbances characteristic of full hGH administration.[1]
The long-term safety beyond ~24 weeks of continuous administration was not characterized because development was halted after the failed Phase 2b. Use in 2026 is not guided by a long-term safety dataset.
Dosing is not addressed on this page. Decisions about therapeutic use belong with a licensed prescriber.
Frequently asked questions
Related peptides
Citations
- Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. Journal of Endocrinology and Metabolism. 2013. ↗ Source Pooled safety summary of 6 RCTs, ~900 participants
- 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 β3-AR knock-out mice. Endocrinology. 2001. PMID 11713213
- Amanecia Health editorial. FDA peptide reclassification 2026. amaneciahealth.com. 2026. ↗ Source industry-analysis
- OpenLoop Health editorial. What peptides are becoming legal in 2026? openloophealth.com. 2026. ↗ Source industry-analysis
- World Anti-Doping Agency. The 2026 Prohibited List — S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics. wada-ama.org. 2026. ↗ Source wada
- 2026-05-22Initial page. Heffernan 2001 (animal mechanism), Stier 2013 (pooled safety of 6 human trials including the failed Phase 2b), and regulatory status notes. Editorial emphasis on the fact that AOD-9604 has clearer evidence of efficacy *failure* than most marketed peptides.