AOD-9604

AOD-9604 is a synthetic 16-amino-acid peptide corresponding to the C-terminal region (residues 176-191) of human growth hormone (hGH). The peptide was developed by Metabolic Pharmaceuticals as a candidate anti-obesity agent that retains the lipolytic activity of hGH without the somatogenic effects that drive IGF-1 elevation.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / AOD-9604](https://peppudex.com/peptides/aod-9604).

Overview

The molecular argument for AOD-9604 is that hGH's lipolytic and somatogenic activities map to different regions of the molecule. The C-terminal "lipolytic fragment" hypothesis proposed that residues 176-191 carry the lipid-mobilization effects without engaging the growth-hormone receptor in a way that drives IGF-1 production. Phase 2 trials for obesity did not meet primary endpoints, and the compound was repurposed toward joint and cartilage research, with later interest in osteoarthritis pain.

Mechanism

The proposed mechanism is lipolytic activity via beta-3 adrenergic signaling and inhibition of lipogenesis, without growth-hormone receptor-mediated IGF-1 elevation. Mechanistic studies have been mixed; the lipolytic effect in vitro is dose-dependent but the in-vivo human bioavailability and translational efficacy have not held up in late-phase trials.

See: Growth_hormone, Growth_hormone_receptor.

Evidence

• Phase 2b obesity (2007) · 12-week trial in obese adults at 1 mg/day did not meet primary weight-loss endpoint.
• Veterinary cartilage trials · Phamatech/Metabolic studied AOD-9604 in osteoarthritis pain endpoints; results have been reported in registry data but not consistently in peer-reviewed journals.
• GRAS status as a food ingredient · AOD-9604 received Generally Recognized as Safe status in some jurisdictions for limited food-supplement use; the FDA has not approved it as a drug.

Dosing literature

Clinical trials have used subcutaneous 1 mg/day. Some compounded human-use formulations (in jurisdictions where compounding is permitted) have used similar dosing. The wiki does not recommend any human dose; AOD-9604 has not met its clinical-trial endpoints for obesity.

Pharmacokinetics

AOD-9604 has a plasma half-life of approximately 30 minutes after subcutaneous injection. Despite the short half-life, claimed lipolytic effects are reported to persist beyond the elimination window, attributed to downstream beta-3 adrenergic signaling activation. Most published research dosing is daily subcutaneous administration.

Storage

Lyophilized AOD-9604 is stable at –20 °C for at least 24 months. Once reconstituted with bacteriostatic water, store at 2-8 °C and use within 28 days.

Regulatory status

• United States. Not FDA-approved as a drug. Limited food-ingredient GRAS history.
• Australia. AOD-9604 was placed on the Australian TGA Schedule 4 (prescription medicine) in 2020.
• WADA. Growth hormone fragments are prohibited at all times under S2 (peptide hormones, growth factors, related substances) on the [WADA Prohibited List](https://www.wada-ama.org/en/prohibited-list).

Side effects (from published clinical literature)

Phase 2b trials in obesity reported a benign tolerability profile relative to native growth hormone. AOD-9604 lacks the IGF-1 elevation, glucose intolerance, and hypertrophic effects associated with full-length growth hormone because it is a C-terminal fragment that does not engage the GH receptor in the canonical somatogenic mode. No major adverse-event signals beyond mild injection-site reactions and occasional headaches were reported.

See also

• Growth_hormone · parent molecule
• Tesamorelin · upstream GHRH analog
• Reconstitution · vial-prep math
• [Peppudex card · AOD-9604](https://peppudex.com/peptides/aod-9604) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Heffernan M, et al. "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice." Endocrinology. 2001;142(12):5182-9. PMID 11713213.
• Ng FM, et al. "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone." Horm Res. 2000;53(6):274-8. PMID 11146368.