AOD-9604

AOD-9604

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hGH fragment 177-191, a lipolytic peptide that retains the fat-reducing activity of human growth hormone without IGF-1 elevation or diabetogenic effects.

Quick Facts

Property Value
Also Known As AOD-9604, hGH Frag 177-191, Anti-Obesity Drug 9604, Tyr-hGH Fragment 177-191
Category Metabolic / Weight Loss
Sequence hGH residues 177-191, 15 amino acids with N-terminal tyrosine addition
Molecular Weight ~1815.1 Da
Molecular Formula C78H123N21O23S2
PubChem CID 9831659
Administration SubQ / Oral
Typical Dose Range 250-500 mcg/day SubQ; 1-5 mg/day oral (from literature)
Half-Life Unknown (short, estimated minutes)
Storage Lyophilized: -20C for 1-2 years; Reconstituted: 2-8C, use within 2-3 weeks
FDA Status Not approved. Phase IIb clinical trial completed for obesity (2007) but development terminated due to insufficient efficacy. Note: TGA (Australia) has listed AOD-9604 as a complementary medicine ingredient for joint/cartilage health (osteoarthritis), which is a distinct regulatory pathway from FDA drug approval.
WADA Status Prohibited (S0 – Non-Approved Substances)

Mechanism of Action

AOD-9604 represents the C-terminal fragment of human growth hormone (residues 177-191) with an added tyrosine residue at the N-terminus. This fragment retains the lipolytic activity of full-length hGH through a novel mechanism that is entirely independent of GH receptor binding. Critically, AOD-9604 does NOT bind the growth hormone receptor and therefore does not induce IGF-1 elevation, insulin resistance, or other somatotropic side effects associated with full hGH administration (PMID 11146367).

The primary metabolic mechanism involves stimulation of lipolysis and simultaneous inhibition of lipogenesis in adipose tissue. Studies in obese Zucker rats and ob/ob mice demonstrated that AOD-9604 enhances fat oxidation and reduces body fat accumulation without affecting lean mass, food intake, or circulating IGF-1 levels (PMID 11673763). The lipolytic activity appears to involve upregulation of beta-3 adrenergic receptor (beta3-AR) expression in adipose tissue, amplifying catecholamine-stimulated lipolysis.

Oral administration studies have confirmed bioactivity via the GI route, with AOD-9604 demonstrating effects on lipid metabolism parameters including reduced circulating triglycerides and improved fat oxidation markers in animal models (PMID 10950816). Additionally, AOD-9604 has shown chondroprotective activity in preclinical models, stimulating chondrocyte repair and proteoglycan synthesis while inhibiting cartilage-degrading enzymes such as MMP-13, supporting its potential role in osteoarthritis management (PMID 26275694).

Key Research Areas

  1. Obesity and fat loss – Primary research domain; demonstrated lipolytic activity without diabetogenic effects in multiple animal models and Phase IIb human trial
  2. Lipid metabolism – Enhancement of fat oxidation, reduction of lipogenesis, and modulation of circulating lipid profiles
  3. Osteoarthritis / joint health – Chondroprotective effects via cartilage repair stimulation and MMP-13 inhibition (basis for Australian TGA listing)
  4. Body composition – Fat reduction without lean mass loss, distinguishing it from caloric restriction
  5. Anti-doping detection – Development of detection methods for sports drug testing
  6. Oral peptide bioavailability – Demonstrated oral bioactivity, relevant to peptide drug delivery research

Evidence Level Summary

Evidence Type Count Notes
Human RCTs 1 Phase IIb obesity trial (terminated 2007, insufficient efficacy)
Human observational 0
Animal in vivo 5 Obese Zucker rats, ob/ob mice, rabbit OA model
In vitro 1 Metabolism and detection studies
Systematic reviews 0

All current evidence for AOD-9604 is preclinical (Level V). One Phase IIb human obesity trial was conducted by Metabolic Pharmaceuticals but was terminated in 2007 for insufficient efficacy. No completed human RCTs demonstrating therapeutic benefit exist in the published literature. The evidence base consists entirely of animal studies and reviews.

Clinical Applications

  • Fat Loss — Stimulates lipolysis and inhibits lipogenesis without IGF-1 elevation
  • Weight Management — Body fat reduction without lean mass compromise
  • Injury Recovery — Chondroprotective and cartilage repair properties (OA model data)

Protocols Using This Peptide

Ageless Peps Products

  • AP-AOD9604-Vial — AOD-9604 Vial, SubQ, $48 (WC 651)

Dosing Reference

Research Dosing Ranges (from literature)

Route Dose Range Frequency Duration Source
SubQ 250-500 mcg Once daily (AM, fasted) 8-12 weeks Practitioner consensus; Phase II trial design
Oral 1-5 mg Once daily (fasted) 8-12 weeks PMID 10950816 (animal extrapolation)

Cycling

Typical cycling: 8-12 weeks on / 4 weeks off. Fasted administration is strongly recommended (food blunts GH-fragment activity). Morning dosing preferred; exercise within 1-2 hours post-injection may amplify lipolytic effect.

Contraindications & Safety

  • Contraindications: Active malignancy (prudent caution despite absent IGF-1 induction); pregnancy/breastfeeding (insufficient data)
  • Common side effects: Mild injection site reactions; transient hypoglycemia if administered in non-fasted state; headache
  • Drug interactions: No significant interactions documented; theoretical additive hypoglycemia with insulin or sulfonylureas
  • Pregnancy/nursing: Insufficient data; not recommended
  • Special populations: No specific renal/hepatic data; pediatric use not studied

Synergistic Combinations

  • CJC-1295 NO DAC + Ipamorelin + AOD-9604 — GH axis optimization + targeted lipolysis; complementary mechanisms
  • 5-Amino-1MQ + AOD-9604 — Dual metabolic attack: NAD+ restoration + direct lipolysis
  • BPC-157 + AOD-9604 — Tissue repair + joint protection synergy
  • Semaglutide or Tirzepatide + AOD-9604 — GLP-1 appetite suppression + direct fat oxidation

Related Research

PMID Title Year Study Type
PMID-11146367 – AOD9604 Metabolic Studies Lipolytic Domain Metabolic studies of the lipolytic domain of hGH (AOD9604) 2001 Animal in vivo
PMID-11673763 – AOD9604 Fat Oxidation and Weight Loss in Obese Mice Fat oxidation and weight loss in obese mice treated with AOD9604 2001 Animal in vivo
PMID-10950816 – AOD9604 Oral Effects on Lipid Metabolism Oral AOD9604 effects on lipid metabolism 2000 Animal in vivo
PMID-11713213 – The effects of human GH and its lipolytic fragment (AOD9604) The effects of human GH and its lipolytic fragment on lipid metabolism 2001 Animal in vivo
PMID-15134286 – AOD-9604 Clinical Development Review AOD-9604 clinical development review 2004 Review
PMID-25208511 – Detection and in vitro metabolism of AOD9604. Detection and in vitro metabolism of AOD9604 2014 In vitro
PMID-26275694 – AOD9604 Intra-articular Injection Rabbit OA AOD9604 intra-articular injection in rabbit OA model 2016 Animal in vivo
PMID-41966639 – Peptide Therapies for Musculoskeletal and Athletic Performance Peptide therapies for musculoskeletal and athletic performance 2024 Review

References

  • PMID 11146367 — Metabolic studies, lipolytic domain identification
  • PMID 11673763 — Fat oxidation and weight loss in obese mice
  • PMID 10950816 — Oral AOD9604 effects on lipid metabolism
  • PMID 15134286 — Clinical development review
  • PMID 26275694 — Intra-articular OA model
  • PMID 25208511 — Detection and metabolism

Related

#peptide #metabolic #subq #oral