AOD-9604
hGH Fragment 176-191 (Anti-Obesity Drug 9604)
AOD-9604 is a synthetic peptide corresponding to amino acids 176–191 of human growth hormone, with an added tyrosine residue. It was developed specifically to isolate the fat-metabolising properties of hGH without stimulating IGF-1 production or affecting insulin sensitivity — the key concerns with full hGH therapy.
Mechanism of Action
AOD-9604 mimics the lipolytic (fat-breaking) action of the C-terminal fragment of growth hormone at the beta-3 adrenergic receptor in adipocytes. By activating beta-3 receptors, it promotes lipolysis (fat cell triglyceride breakdown) and inhibits lipogenesis (new fat formation) through similar pathways to full hGH, but without engaging the anabolic growth pathway.
Critically, AOD-9604 does not bind the GH receptor and does not stimulate IGF-1 production. This dissociation of metabolic and anabolic hGH effects is the core therapeutic rationale for AOD-9604 development as a potential anti-obesity agent.
In obese animal models, AOD-9604 reduced visceral fat accumulation, improved metabolic parameters, and improved insulin sensitivity — despite no direct insulin receptor interaction.
Research Evidence
AOD-9604 completed Phase 2b trials for obesity (METRO study) before development was discontinued. Despite clear mechanistic rationale and positive preclinical data, the Phase 2b trial did not demonstrate statistically significant weight loss versus placebo at the dose tested. Research interest continues, particularly for non-obesity metabolic indications.
AOD-9604 Stimulates Lipolysis in Rodent Adipocytes
hGH176-191 stimulated in vitro lipolysis in rat adipocytes and inhibited lipogenesis at concentrations that had no effect on glucose uptake or IGF-1 secretion, confirming selectivity for fat metabolism pathways.
Typical Research Protocol
Phase 2b trials used 1mg/day orally without significant effect. SC delivery at 300–500mcg is the current research-context standard. Does not require calorie cycling to time with GH pulses (unlike GHRP/GHRH protocols).
Safety Profile
Reported Side Effects
- Injection site redness
- Mild flushing
- Headache (transient)
Contraindications
- Active cancer (theoretical, given GH receptor homology)
- Pregnancy (no data)
Common Research Stacks
Frequently Asked Questions
Does AOD-9604 affect IGF-1 or insulin?
No — this is its key differentiator from full hGH. AOD-9604 does not bind the growth hormone receptor, does not stimulate IGF-1 production, and has no measurable effect on insulin sensitivity at studied doses. This profile makes it safer from a metabolic standpoint than full hGH for weight management.
Why did AOD-9604 fail in clinical trials?
AOD-9604 failed to show statistically significant weight loss in the Phase 2b METRO trial at the oral dose tested (1mg/day). The failure was attributed to insufficient dose finding prior to Phase 2b and the challenge of oral bioavailability. Preclinical data at SC doses remained positive, and many researchers believe the compound was not given a fair test at the oral dose selected.
Can AOD-9604 be combined with other fat-loss peptides?
Yes — AOD-9604 is often combined with GH-stimulating peptides like Ipamorelin or CJC-1295. AOD-9604 contributes direct lipolytic activity (beta-3 adrenergic receptor activation in fat cells) while GHRPs/GHRHs drive the GH pulse that improves overall metabolic rate and body composition. The combination targets fat loss through complementary pathways.
Does AOD-9604 need to be taken fasted?
Pre-workout or morning fasted dosing is generally recommended to maximise the metabolic window. Unlike GHRP/GHRH protocols that require strict fasting to preserve GH pulse amplitude, AOD-9604's mechanism is more direct (beta-3 receptor activation) and less affected by insulin levels. Still, fasted use is the standard research approach.
Is AOD-9604 legal to purchase?
AOD-9604 exists in a similar regulatory grey area as most research peptides. It is not FDA-approved for any indication and was removed from the TGA approved list in Australia. It is available as a research chemical. Legal status varies by jurisdiction — verify current regulations in your country before obtaining.
Key Research References
- Ng FM et al. (2000). Metabolic studies of a growth hormone fragment. Mol Cell Endocrinol.
- Heffernan M et al. (2001). The effects of the GH fragment AOD-9604 on adiposity. Endocrinology.
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