AOD-9604

AOD-9604 (Advanced Obesity Drug-9604) is a modified fragment of human growth hormone comprising amino acids 177-191, with a tyrosine residue added at the N-terminus for stability. Developed by Metabolic Pharmaceuticals in Australia, AOD-9604 was designed to isolate the fat-metabolizing activity of GH while eliminating its growth-promoting and diabetogenic effects.

Mechanism of Action

AOD-9604 mimics the lipolytic (fat-burning) action of the C-terminal fragment of growth hormone. It stimulates lipolysis (fat breakdown) and inhibits lipogenesis (fat formation) by interacting with the beta-3 adrenergic receptor pathway. Critically, it does not affect IGF-1 levels, blood glucose, or tissue growth, meaning it produces fat loss without the metabolic side effects of full-length GH.

Research has also identified chondroprotective properties, with AOD-9604 stimulating proteoglycan and collagen production in articular cartilage, leading to investigation for osteoarthritis treatment.

Clinical Research

AOD-9604 completed Phase IIb clinical trials for obesity (Stier et al., 2013). While the oral formulation showed a trend toward greater weight loss versus placebo, results did not reach statistical significance, and the obesity drug program was discontinued. However, the peptide subsequently received FDA GRAS (Generally Recognized as Safe) status as a food additive in 2014.

The osteoarthritis program has shown more promise. Preclinical studies demonstrated that AOD-9604 stimulates cartilage repair by promoting chondrocyte proliferation and matrix synthesis. A Phase II clinical trial for knee osteoarthritis (intra-articular injection) showed improvement in pain and function scores.