AOD9604

Also known as: AOD-9604, AOD 9604, Tyr-hGH(177-191), Anti-Obesity Drug 9604, sh-Oligopeptide-74

Evidence: Preclinical

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Overview

Modified hGH fragment (Tyr plus hGH 177-191) that reduced weight gain and raised fat oxidation in obese rodents; six human trials found no IGF-1 or glucose effects, with efficacy results unpublished.

AOD9604 is tyrosine-hGH(177-191), a synthetic analog of the C-terminal lipolytic region of human growth hormone developed at Monash University and Metabolic Pharmaceuticals. In obese mice and Zucker rats it reduced weight gain, raised fat oxidation and lipolysis, and unlike hGH did not cause insulin resistance or bind the GH receptor (Ng 2000; Heffernan 2001). Six randomised placebo-controlled human trials in about 900 adults used IV doses of 25 to 400 mcg/kg or oral doses of 0.25 to 54 mg; the published summary reports safety only: no change in IGF-1 or glucose tolerance and no antibodies (Stier 2013). Weight-loss results of the 12- and 24-week trials were never published in a peer-reviewed journal. Intra-articular injection aided cartilage repair in a rabbit osteoarthritis model (Kwon 2015). WADA prohibits it.

Benefits

Reduced body weight gain and increased fat oxidation and lipolysis (obese mice and rats), cartilage regeneration after intra-articular injection (rabbit); no effect on IGF-1 or glucose tolerance (human RCTs, safety data only)

Dosing reference

Research dose: 300 to 500 mcg once daily subcutaneously (community range); human trials used oral 0.25 to 30 mg daily or single IV doses of 25 to 400 mcg/kg
Range: 300 to 500 mcg, 1x daily
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 5 mg

Community protocols inject 300 to 500 mcg subcutaneously, often fasted in the morning. All published human dosing was oral (capsules 1 to 54 mg; tablets 0.25 to 1 mg for 24 weeks) or single IV infusions of 25 to 400 mcg/kg over 20 minutes (Stier 2013). No subcutaneous human study exists.

Mechanism

AOD9604 corresponds to the C-terminal region of hGH that carries its lipolytic and antilipogenic activity. In rodent adipose tissue it increased lipolysis and reduced lipogenesis (Ng 2000). Its effect on weight is not mediated through the beta-3 adrenergic receptor, although it raises beta-3 receptor expression, and it still raised fat oxidation acutely in beta-3 knockout mice (Heffernan 2001, Endocrinology). It does not compete for the hGH receptor or drive hGH-receptor cell proliferation (Heffernan 2001, Int J Obes). In serum it is degraded to a stable CRSVEGSCG fragment (Cox 2015). Its receptor is not identified. Chondroprotective effects are proposed from one rabbit study (Kwon 2015).

Evidence

Preclinical: animal or in vitro data only

Reduced body weight gain and raised fat oxidation and plasma glycerol in obese mice over 14 days without hyperglycaemia or hGH-receptor binding (Heffernan et al., 2001)
Oral 500 mcg/kg daily for 19 days halved weight gain in obese Zucker rats without impairing insulin sensitivity (Ng et al., 2000)
Six placebo-controlled human trials (about 900 adults; IV 25 to 400 mcg/kg, oral 0.25 to 54 mg daily up to 24 weeks): no change in IGF-1 or glucose tolerance, no antibodies, adverse events similar to placebo (Stier et al., 2013)
Weekly intra-articular 0.25 mg improved cartilage scores in a rabbit osteoarthritis model, more so with hyaluronic acid (Kwon et al., 2015)
Human-trial status: obesity programme ended without published efficacy results; no registered trial is active. A 2013 GRAS determination was by an industry-commissioned panel, not FDA

References

Side effects

In six placebo-controlled trials (Stier 2013), headache was the most common event, followed by diarrhoea, flatulence and nausea, at rates similar to placebo; 54 mg oral doses produced more headache and GI upset. Mild euphoria was reported by 5 of 23 subjects after IV dosing and not with placebo. IGF-1, glucose tolerance, ECG and safety labs did not change and no anti-AOD9604 antibodies were found. Five cancers (skin, breast, melanoma) arose in the 12-week trial and were judged unrelated by investigators. Injection-site irritation is commonly reported with subcutaneous use (anecdotal); no subcutaneous human data exist. Regulatory: AOD-9604 is in the 503A withdrawn-nomination table of FDA's compounding safety-risk page, page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks

Storage

Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located
Lyophilized: 24+ months at room temperature
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: No human PK published; the parent peptide degraded in serum and urine in vitro, leaving a stable CRSVEGSCG metabolite (Cox 2015)
Bioavailability: Not reported. Oral dosing was active in obese rodents (Ng 2000) and used in all long human trials (Stier 2013); no subcutaneous PK data
Molecular weight: 1815.1 Da
Sequence: YLRIVQCRSVEGSCGF [disulfide Cys7-Cys14]