AOD-9604
Advanced Obesity Drug | Modified hGH Fragment 176-191
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.
Daily dose
250-500mcg
Frequency
1x daily
Cycle length
8-12 weeks
Storage
2-8°C
Key benefits
Stimulates fat loss through lipolysis without growth hormone side effects. Does not increase IGF-1 or affect glucose metabolism. Shows promise for cartilage repair. Excellent safety profile in ~900 clinical trial participants.
How it works
AOD-9604 acts through a dual mechanism: acute lipolysis via receptor-independent pathways, and chronic metabolic remodeling via beta-3 adrenergic receptor upregulation in adipose tissue. Does not bind the GH receptor, does not increase IGF-1, and does not cause hyperglycemia or cell proliferation.
Dosage protocols
Goal
Fat loss
Dose
250-300mcg · Once daily
Route
Subcutaneous
Goal
Enhanced fat loss
Dose
400-500mcg · Once daily
Route
Subcutaneous
Goal
Joint support
Dose
250mcg · Once daily
Route
Subcutaneous
Goal
Conservative start
Dose
200mcg · Once daily
Route
Subcutaneous
Research indications
fat Loss
joint
Administration
Interactions
Safety notes
Excellent safety in 6 RCTs (~900 participants) — zero serious adverse events
158,989 US compounding prescriptions with zero FAERS adverse events (2024)
Does not affect blood glucose, insulin, or IGF-1
No anti-AOD-9604 antibodies detected in trials
May cause mild injection site reactions
Not recommended during pregnancy
WADA prohibited at all times — S.0 category
Long-term safety beyond 24 weeks not studied
Research studies
Human Safety & Tolerability — Pooled Analysis of 6 RCTs (2013)
~900 obese adults | Oral 0.25-54mg/day & IV 25-400µg/kg | 6 trials | Safety indistinguishable from placebo
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 →Phase IIa — Oral AOD-9604 for Obesity (2001-2002)
300 obese adults | Oral 0.25, 0.5, 1.0mg/day | 12 weeks | Significant weight loss at 1mg
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 →Phase IIb OPTIONS Trial — Oral AOD-9604 for Obesity (2006)
536 obese adults | Oral dosing | 24 weeks | Failed primary endpoint
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 →Osteoarthritis Cartilage Repair Study (2015)
Rabbits (n=32) | 0.25mg weekly intra-articular | 4-7 weeks | Enhanced cartilage regeneration
Combined AOD-9604 and hyaluronic acid injections were more effective than either alone. Lameness recovery was fastest in the combination group (11±4 days vs 25±2 days for controls). AOD-9604 enhanced cartilage regeneration without stimulating IGF-1.
View study →Detection and Metabolism Study (2015)
In vitro | Various concentrations | Metabolite identification
Validated detection method with 50 pg/mL limit. Identified six potential metabolites. The metabolite CRSVEGSCG proved significantly more stable than the parent compound in serum. Confirmed peptide sequence structure.
View study →Fat Oxidation and Weight Loss in Obese Mice (2001)
Mice | Mini-osmotic pumps | 14 days | Significant weight reduction and increased fat oxidation
Both hGH and AOD-9604 significantly reduced body weight gain in obese mice, correlated with increased in vivo fat oxidation and plasma glycerol levels. Importantly, AOD-9604 did not cause hyperglycemia or reduce insulin secretion like full hGH.
View study →Beta-3 Adrenergic Receptor Mechanism Study (2001)
Mice & Beta-3-AR knockout mice | 14 days | Increased beta-3-AR expression, reduced adipose tissue
Treatment reduced body weight and adipose tissue while increasing beta-3-AR expression to levels comparable with lean mice. In knockout mice, chronic effects were abolished but acute energy expenditure increases persisted.
View study →Oral Administration Effects on Lipid Metabolism (2000)
Mice | Oral daily | 30 days | Reduced lipogenesis, increased lipolysis
From day 16 onward, body weight gain was significantly lower than controls. The compound significantly reduced lipogenic activity and increased lipolytic activity in adipose tissue. Effects also demonstrated on isolated human adipose tissue.
View study →Antilipogenic Action of C-Terminal hGH Fragment (1993)
In vitro | Various concentrations | Demonstrated antilipogenic activity
Foundational study showing the synthetic C-terminal peptide fragment demonstrated antilipogenic activity identical to intact hGH. Established that the antilipogenic functional domain resides in the C-terminal region of growth hormone.
View study →