AOD-9604: Complete Guide

AOD-9604 was developed by Professor Frank Ng at Monash University in Australia through a systematic investigation of which region of the growth hormone molecule is responsible for its fat-metabolizing effects. Researchers identified that the C-terminal fragment (amino acids 176-191) of human growth hormone retained lipolytic activity independent of the full molecule's growth and metabolic effects.

The "AOD" designation stands for "Anti-Obesity Drug," reflecting the compound's original development purpose. The fragment was modified with an additional tyrosine at the N-terminus to improve stability and activity, resulting in the 17-amino-acid peptide known as AOD-9604.

The critical innovation of AOD-9604 is what it does not do. Full-length growth hormone stimulates lipolysis but also raises blood glucose (diabetogenic effect), increases IGF-1 (growth-promoting), and can cause fluid retention, joint pain, and carpal tunnel syndrome. AOD-9604 was designed to deliver the fat-metabolizing benefits without these unwanted effects, and research has largely confirmed this selectivity.

AOD-9604 mimics the way natural growth hormone regulates fat metabolism through two complementary mechanisms:

• Stimulation of lipolysis: AOD-9604 activates beta-3 adrenergic receptors on adipocytes, stimulating hormone-sensitive lipase (HSL) to break down stored triglycerides into free fatty acids and glycerol for energy utilization.
• Inhibition of lipogenesis: Simultaneously, AOD-9604 suppresses the formation of new fat by inhibiting the activity of lipogenic enzymes including fatty acid synthase and acetyl-CoA carboxylase.

This dual action — breaking down existing fat while preventing new fat formation — distinguishes AOD-9604 from compounds that only address one side of the fat metabolism equation.

Importantly, AOD-9604 does not bind to the growth hormone receptor in a way that activates the JAK-STAT signaling pathway responsible for GH's growth-promoting effects. This is why it does not increase IGF-1 levels, stimulate tissue growth, or impair glucose metabolism.

Preclinical Studies

Animal studies at Monash University demonstrated that AOD-9604 reduced body fat in obese mice without affecting lean mass, food intake, or blood glucose levels. Treated animals showed increased fat oxidation and decreased fat accumulation compared to controls. Notably, the peptide was effective in both genetic and diet-induced obesity models.

Human Clinical Trials

AOD-9604 progressed through Phase 2 clinical trials in obese human subjects. Results showed:

• Statistically significant fat loss compared to placebo at the 1mg oral dose
• No effect on IGF-1 levels, confirming the absence of growth-promoting activity
• No adverse effects on glucose tolerance or insulin sensitivity
• No antibody formation against the peptide

However, the overall magnitude of weight loss in Phase 2 trials was modest, and the compound did not advance to Phase 3 for the obesity indication. It subsequently pursued a different regulatory pathway, receiving FDA GRAS status for use as a food ingredient.

Cartilage and Joint Research

More recent research has explored AOD-9604's potential in cartilage repair. Studies published in the Journal of Stem Cells and Regenerative Medicine found that AOD-9604 stimulated proteoglycan and collagen synthesis in chondrocytes. This has led to interest in AOD-9604 for osteoarthritis and joint health applications, and an intra-articular formulation is under investigation in Australia.

AOD-9604 dosing in research settings:

Route	Typical Research Dose	Timing
Subcutaneous	250–500 mcg daily	Morning, fasted state
Oral	1 mg daily (clinical trial dose)	Before meals

Fasted administration is generally used in research because insulin inhibits lipolysis, and post-meal insulin elevations could theoretically counteract AOD-9604's mechanism. The peptide is reconstituted using standard bacteriostatic water protocols — use the peptide calculator for volumes and the reconstitution guide for step-by-step instructions.

For detailed protocols, visit the AOD-9604 dosage guide.

AOD-9604 has one of the strongest safety profiles among research peptides, supported by both clinical trial data and FDA GRAS determination:

• No effect on blood glucose: Multiple studies confirmed AOD-9604 does not impair glucose tolerance or insulin sensitivity — a key advantage over full-length growth hormone
• No IGF-1 elevation: AOD-9604 does not increase IGF-1, eliminating concerns about tissue growth stimulation
• No antibody formation: Clinical trials detected no anti-AOD-9604 antibodies, suggesting low immunogenicity
• Injection site reactions: Mild, transient redness at injection sites — the most common reported event
• No significant adverse events: Clinical trials reported no serious adverse events attributable to AOD-9604

The FDA GRAS status (for oral use as a food ingredient) further supports the safety profile, as GRAS determination requires a consensus of qualified experts that the substance is safe under intended conditions of use. More in the AOD-9604 side effects guide.

Peptide	Mechanism	GH Effects?	FDA Status
AOD-9604	GH fragment — lipolysis only	No (no IGF-1 increase)	GRAS (food ingredient)
Tesamorelin	GHRH analog — stimulates GH release	Yes (raises IGF-1)	FDA-approved drug
Retatrutide	GLP-1/GIP/glucagon triple agonist	No	Phase 3 trials
Tirzepatide	GLP-1/GIP dual agonist	No	FDA-approved drug

AOD-9604 occupies a unique niche: it targets fat metabolism directly through the GH fragment pathway without the systemic hormonal effects of GHRH analogs or the appetite/GI effects of GLP-1 agonists. However, its magnitude of weight loss in trials was more modest compared to GLP-1-based drugs. For a broader comparison, see the peptides for weight loss guide.