AOD-9604

AOD-9604 (Advanced Obesity Drug 9604) is a synthetic peptide fragment derived from the C-terminal end of human growth hormone (HGH), specifically amino acids 176-191. It was developed by Professor Frank Ng at Monash University in Australia, based on the discovery that this specific region of HGH is responsible for its fat-burning (lipolytic) effects, while the growth-promoting and diabetogenic effects reside in other regions of the molecule.

The key innovation of AOD-9604 is that it retains the fat-metabolizing activity of growth hormone without the negative metabolic effects associated with full HGH — namely, it does not increase IGF-1 levels, does not impair glucose tolerance, and does not promote tissue growth. This makes it a targeted fat-loss agent without the broader hormonal effects of growth hormone therapy.

AOD-9604 has been granted GRAS (Generally Recognized As Safe) status by the FDA for use as a food substance, though it is not approved as a pharmaceutical drug. It has completed Phase 2 clinical trials for obesity with mixed results.

AOD-9604 mimics the lipolytic mechanism of growth hormone:

Beta-3 adrenergic receptor stimulation: AOD-9604 stimulates lipolysis (fat breakdown) in adipose tissue through interaction with beta-3 adrenergic receptors, the same receptors activated by the fat-burning region of full-length growth hormone.

Inhibition of lipogenesis: Beyond promoting fat breakdown, AOD-9604 also inhibits lipogenesis — the process of converting non-fat nutrients into stored fat. This dual action (increased breakdown + reduced new fat storage) contributes to its fat-reducing effects.

No IGF-1 elevation: Unlike full HGH or GHRH analogs (like tesamorelin), AOD-9604 does not stimulate the liver to produce IGF-1. This means it does not carry the risks associated with elevated IGF-1 levels, including potential cancer promotion and glucose dysregulation.

Cartilage repair (emerging): More recent research has explored AOD-9604's potential for stimulating chondrocyte (cartilage cell) proliferation, opening possible applications in osteoarthritis treatment. Australian company Regeneus has been developing it for this indication.

Phase 2 clinical trial (obesity): A 24-week randomized, placebo-controlled trial in 300 obese individuals tested AOD-9604 at oral doses of 1, 5, 10, and 20 mg daily. Results showed a trend toward greater weight loss in the AOD-9604 groups compared to placebo, but the differences did not reach statistical significance at the primary endpoint. However, the study demonstrated excellent safety and tolerability.

Animal studies: Rodent studies have consistently shown significant reductions in body fat with AOD-9604 treatment, without changes in IGF-1 levels or glucose tolerance — confirming the peptide's selectivity for fat metabolism without broader growth hormone effects.

Cartilage research: In vitro and animal studies have shown that AOD-9604 stimulates proteoglycan and collagen synthesis in cartilage tissue, suggesting potential as an osteoarthritis treatment. Phase 2 trials for this indication have been conducted in Australia.

Safety data: Across all clinical trials, AOD-9604 has demonstrated an excellent safety profile with adverse events comparable to placebo. The FDA's GRAS determination further supports its safety for human consumption.

Injectable: Common research doses range from 250-500 mcg per day, administered subcutaneously in the abdominal area (near fat deposits) on an empty stomach. Morning administration before breakfast is commonly recommended.

Oral: Based on clinical trial data, oral doses of 1-20 mg daily have been studied. Oral bioavailability is significantly lower than injectable, hence the much higher oral doses.

Timing: Administer on an empty stomach, ideally 30 minutes before food. Food intake, particularly carbohydrates, may interfere with the lipolytic mechanism.

Duration: Typical research cycles run 8-12 weeks. Some protocols extend to 20+ weeks for continued fat loss effects.

AOD-9604 has one of the best safety profiles of any peptide, largely because it does not affect the broader growth hormone axis:

Reported side effects (mild): Injection site reactions, mild headache, indigestion or nausea (oral form), and transient flu-like symptoms (rare).

What it does NOT cause (unlike full HGH): No IGF-1 elevation, no glucose impairment / insulin resistance, no water retention or edema, no joint pain or carpal tunnel, and no acromegaly risk.

FDA GRAS status: The fact that AOD-9604 has been granted GRAS status by the FDA for food use provides additional reassurance regarding its safety profile.