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Overview
What is AOD-9604?
AOD-9604 is a modified fragment of human growth hormone (hGH amino acids 177-191) with an N-terminal tyrosine, developed by Professor Frank Ng at Monash University in collaboration with Metabolic Pharmaceuticals Ltd (Australia). It stimulates lipolysis and inhibits lipogenesis through beta-3 adrenergic receptor upregulation without the growth-promoting effects of full hGH. Six clinical trials enrolling ~900 participants demonstrated excellent safety but the pivotal Phase IIb trial failed to show clinically meaningful weight loss, leading to development termination in 2007. Australia's TGA has approved it as iTRAM for intra-articular knee osteoarthritis. It is not FDA-approved and is WADA-prohibited.
Key Benefits
Stimulates fat loss through lipolysis without growth hormone side effects. Does not increase IGF-1, affect glucose metabolism, or cause insulin resistance. Also shows promise for cartilage repair. Note: subcutaneous injection is community-derived — all six clinical trials used oral dosing.
Mechanism of Action
AOD-9604 acts through a dual mechanism: acutely, it stimulates lipolysis and energy expenditure through receptor-independent pathways; chronically, it upregulates beta-3 adrenergic receptor (β3-AR) expression in adipose tissue (restoring levels to lean-equivalent) to sustain fat oxidation. This was confirmed by knockout mouse studies where acute effects persisted but chronic weight loss was abolished without β3-AR. Crucially, it does not bind the GH receptor, does not increase IGF-1, and does not cause hyperglycemia or cell proliferation.
Molecular Information
Weight
1,815.1 Da
Length
17 amino acids
Type
Modified hGH C-terminal fragment
Amino Acid Sequence:
YLRIVQCRSVEGSCGF (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe)
* hGH fragment 176-191 with N-terminal tyrosine addition; contains disulfide bond between Cys183 and Cys189
Pharmacokinetics
Research Indications
Fat Loss / Lipolysis
Primary research indication. Increases fat oxidation, plasma glycerol levels, and reduces body weight in obese models without affecting glucose metabolism.
Lipogenesis Inhibition
Reduces fat synthesis and storage in adipose tissue. Effects demonstrated in both animal models and isolated human adipose tissue.
Metabolic Safety
Unlike full hGH, does not cause hyperglycemia, reduce insulin secretion, or increase insulin resistance. Safer metabolic profile.
Research Protocols
Disclaimer
These are commonly discussed research protocols and not medical advice. Consult a healthcare provider before use.
Timing
Best administered in the morning on an empty stomach. Wait 30 minutes before eating. Some research protocols suggest injection into abdominal subcutaneous fat for localized effect.
Peptide Interactions
How to Reconstitute
Important
Always use bacteriostatic water (BAC). Sterile technique is essential.
Allow vial to reach room temperature (15-20 minutes)
Calculate required BAC water volume using calculator below
Draw BAC water into syringe
Inject slowly down vial side (not directly onto powder)
Gently swirl until dissolved (never shake vigorously)
Store reconstituted solution at 2-8°C and use within 28 days
Quality Indicators
White Lyophilized Powder
Should appear as white to off-white powder or cake. Uniform appearance indicates proper freeze-drying.
Clear Solution After Reconstitution
When mixed with BAC water, solution should be crystal clear without particles or cloudiness.
Certificate of Analysis
Quality suppliers provide CoA showing purity >98% by HPLC and confirmed amino acid sequence.
No FDA Drug Approval
Not FDA-approved. FDA PCAC recommended against 503A bulks list in Dec 2024. TGA (Australia) approved for intra-articular OA as iTRAM only. US compounding status in flux.
SubQ Route Not Clinically Validated
All six clinical trials used oral dosing. Subcutaneous 200-500mcg protocols are community-derived extrapolations without published clinical evidence.
Discolored or Clumped Powder
Yellow discoloration, excessive clumping, or collapsed appearance may indicate degradation.
WADA Prohibited
Banned by World Anti-Doping Agency. Athletes subject to testing must not use this compound.
What to Expect
- Week 1-2: Minimal noticeable effects, compound building in system
- Week 3-4: May notice subtle changes in body composition
- Week 5-8: More noticeable fat loss, especially with diet and exercise
- Week 8-12: Continued fat reduction, improved body composition
- Side effects: Generally well-tolerated, mild injection site reactions possible
Side Effects & Safety
- Excellent safety in 6 RCTs (~900 participants) — zero serious adverse events, profile indistinguishable from placebo
- 158,989 US compounding prescriptions filled with zero FDA FAERS adverse event reports (as of 2024)
- Does not affect blood glucose, insulin, or IGF-1 — safer metabolic profile than full hGH
- No anti-AOD-9604 antibodies detected in any trial participant
- May cause mild injection site reactions
- Not recommended during pregnancy or breastfeeding
- WADA prohibited substance — banned at all times under S.0 category
- Long-term safety beyond 24 weeks has not been studied
- FDA recommended against 503A bulks list inclusion in Dec 2024 citing immunogenicity concerns
References
Human Safety & Tolerability — Pooled Analysis of 6 RCTs (2013)
Pooled analysis of all six randomized, double-blind, placebo-controlled clinical trials of AOD-9604. Zero serious adverse events attributed to AOD-9604, zero treatment-related discontinuations. No clinically significant changes in IGF-1, glucose, or insulin. No anti-AOD-9604 antibodies detected in any participant. Adverse events (headache, mild GI symptoms) were comparable to placebo.
View Study (opens in new tab) →Phase IIa — Oral AOD-9604 for Obesity (2001-2002)
Randomized, double-blind, placebo-controlled trial in 300 obese adults. The 1mg/day oral group achieved 2.8kg mean weight loss vs 0.8kg for placebo (statistically significant). This positive result led to the larger Phase IIb OPTIONS trial.
View Study (opens in new tab) →Phase IIb OPTIONS Trial — Oral AOD-9604 for Obesity (2006)
The pivotal Phase IIb multicenter trial. Despite full enrollment of 536 subjects, AOD-9604 showed no statistically significant weight loss vs placebo at 12 or 24 weeks. The trial incorporated intensive diet and exercise, which may have masked modest peptide effects. Development was terminated in March 2007 by Metabolic Pharmaceuticals.
View Study (opens in new tab) →Quick Start Guide
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Community Insights
Self-reported by PepPedia users. Not clinical evidence. Health changes reflect all users, including those taking multiple compounds.
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