HGH Fragment 176-191 (AOD-9604)
/ Synthetic 16-residue C-terminal fragment of human growth hormone (residues 176-191); proposed lipolytic without GH-axis activationALIAS · AOD-9604 · AOD9604 · HGH Fragment 176-191 · Frag 176-191
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Tier 2. Synthetic 16-residue C-terminal fragment of human growth hormone (residues 176-191), originally developed by Metabolic Pharmaceuticals as AOD-9604 for obesity. Phase 2b trial in obesity (Stier 2013, also reported in earlier Heffernan-led studies) failed to meet primary weight-loss endpoint; development for the obesity indication was discontinued. AOD-9604 has separately been positioned as a novel food / nutraceutical ingredient in Australia and the US (FDA Generally Recognized as Safe self-affirmation 2014) without therapeutic approval.
The molecule reproduces the C-terminal sequence of human GH that early biochemical work attributed to a putative lipolytic and anti-lipogenic activity distinct from the somatogenic (GH receptor) and metabolic (IGF-1 mediated) effects of full-length GH. The proposed pharmacology is direct stimulation of beta-3-adrenergic-like lipolytic signalling in adipose tissue without elevation of IGF-1 or insulin resistance. Independent confirmation of the originally reported lipolytic activity has been inconsistent in the broader literature.
Tier 2 by Phase 2b human exposure, but the substantive efficacy claim is negative. Rodent characterisation (Heffernan 2001, Endocrinology) reported lipolytic and body-composition effects in obese rodents. Human Phase 2b in obese adults (Stier 2013, Obes Res Clin Pract; earlier Metabolic Pharmaceuticals-sponsored studies) failed to produce significant weight-loss difference versus placebo on the primary endpoint; the program for obesity was discontinued. No subsequent Phase 3 development.
In published Phase 2b exposure, the 16-residue peptide was well tolerated with no consistent safety signal beyond placebo. No long-term human safety database. The molecule is reported not to elevate IGF-1 or impair glucose tolerance, which was the rationale for distinguishing it from full-length GH; that pharmacological claim rests on the original developer's measurements.
Regulatory status
- FDA status:
- Not FDA-approved
Vendor marketing in the peptide-research channel often presents AOD-9604 as a validated lipolytic with established weight-loss benefit. The most directly relevant human trial - the obesity Phase 2b - failed primary endpoint, and that failure is rarely disclosed in vendor materials. Independent replication of the rodent lipolytic findings is sparse. The repositioning of AOD-9604 as a 'GRAS' food ingredient is a regulatory rather than therapeutic-evidence development.