AOD9604

Overview

AOD9604 is a synthetic peptide fragment derived from the C-terminal domain of human growth hormone (hGH), comprising amino acid residues 176–191 with a tyrosine substitution at the N-terminus. Originally developed by Metabolic Pharmaceuticals as a potential anti-obesity agent, it was designed to replicate the lipolytic properties of hGH without activating the growth hormone receptor or elevating IGF-1 levels.

Mechanism of Action

AOD9604 is proposed to stimulate lipolysis and inhibit lipogenesis through mechanisms involving upregulation of beta-3 adrenergic receptor (β3-AR) expression in adipocytes, modulation of hormone-sensitive lipase (HSL), and inhibition of acetyl-CoA carboxylase. Unlike intact hGH, it does not meaningfully affect insulin sensitivity or glucose metabolism at research doses.

Research and Off-Label Applications

AOD9604 has been investigated for reduction of visceral and subcutaneous adipose tissue, fat oxidation and energy expenditure, cartilage and tissue repair, and as a potential adjunct in metabolic syndrome research. Human clinical trials have produced mixed results, with one 12-week randomized trial reporting approximately 1.8 kg greater fat loss versus placebo. Animal models have demonstrated more pronounced lipolytic effects.

Administration

Typically administered via subcutaneous injection. Research protocols commonly utilize doses of 250–500 mcg per day, often in the morning to align with natural fat metabolism cycles. Higher doses have not demonstrated significantly greater outcomes in clinical data.

Regulatory Status

AOD9604 is not FDA-approved for any indication. It is classified as a prescription-only substance by Australia's Therapeutic Goods Administration (TGA) and is prohibited in competitive sport under WADA regulations. Clinical development was halted in 2007.

Potential Adverse Effects

Generally well tolerated in available research. Reported effects include mild injection site reactions. No significant impact on insulin sensitivity has been reported at research doses.

Pharmacokinetics

Plasma half-life is approximately 4 minutes following intravenous administration; oral forms demonstrate slower absorption kinetics. Sequential N-terminal amino acid truncation is the primary degradation pathway.