Research Applications
Obesity and Weight Management
AOD-9604's primary research application is fat reduction. Phase 2 clinical trials demonstrated modest but statistically significant weight loss (2.8 kg over 12 weeks) in obese subjects. While the Phase 3 trial did not meet its primary endpoint, the peptide demonstrated a favorable safety profile with fat-specific metabolic effects.
Osteoarthritis
AOD-9604 (branded as i-Body in Australia) has been developed for intra-articular injection in knee osteoarthritis. Clinical studies show improved cartilage health markers, reduced pain, and enhanced joint function. This represents the most commercially advanced application of AOD-9604.
Metabolic Syndrome
Research demonstrates AOD-9604 improves multiple components of metabolic syndrome including visceral adiposity, dyslipidemia, and hepatic steatosis (fatty liver) in animal models, without worsening insulin resistance.
Muscle Recovery and Repair
Preclinical studies suggest AOD-9604 may enhance musculotendinous healing, potentially through enhanced local blood flow and growth factor signaling in injured tissue.
Bone Healing
Research indicates AOD-9604 enhances osteoblast differentiation and bone formation, suggesting potential applications in fracture healing and osteoporosis.
Mechanism of Action
Lipolysis Stimulation
AOD-9604 stimulates lipolysis (fat breakdown) through activation of the beta-3 adrenergic receptor (β3-AR) signaling pathway in adipose tissue. It enhances hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity in adipocytes, promoting triglyceride hydrolysis and free fatty acid release — the same lipolytic mechanism as full-length GH but without activation of the GH receptor.
Lipogenesis Inhibition
AOD-9604 inhibits de novo lipogenesis (new fat formation) by suppressing key lipogenic enzymes including fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). This dual action — enhancing fat breakdown while blocking fat synthesis — distinguishes AOD-9604 from agents that only target one pathway.
Independent of GH Receptor
Critically, AOD-9604 does not bind to or activate the growth hormone receptor (GHR) and does not stimulate IGF-1 production. This means it avoids the insulin resistance, fluid retention, and growth-promoting effects of full-length GH or GH secretagogues. The peptide has a distinct, non-GHR mechanism of action that has not been fully characterized but involves direct interaction with adipocyte membrane receptors.
Anti-Lipogenic Gene Regulation
AOD-9604 downregulates transcription factors involved in adipogenesis, including PPARγ and C/EBPα, reducing differentiation of preadipocytes into mature fat cells. It also reduces expression of fat storage genes (perilipin, CIDEA) in white adipose tissue.
Cartilage Repair Activity
Independently of its metabolic effects, AOD-9604 has demonstrated chondroprotective and chondrogenic properties — stimulating proteoglycan synthesis in cartilage and promoting chondrocyte proliferation. This led to investigation of AOD-9604 for osteoarthritis treatment.
Biological Pathways
β3-AR/cAMP/PKA Lipolytic Pathway
AOD-9604's lipolytic action primarily occurs through β3-adrenergic receptor activation in adipocytes. β3-AR signals through Gαs-adenylyl cyclase-cAMP-PKA, phosphorylating HSL and perilipin — enabling HSL translocation to lipid droplets for triglyceride hydrolysis.
AMPK Energy Regulation
AOD-9604 activates AMPK in adipose tissue and liver, enhancing fatty acid oxidation and suppressing lipogenesis. AMPK phosphorylates and inactivates ACC, reducing malonyl-CoA levels and relieving inhibition of CPT-1 (carnitine palmitoyltransferase-1), the rate-limiting enzyme for mitochondrial fatty acid import and oxidation.
SOX9/Aggrecan Chondrogenic Pathway
In cartilage tissue, AOD-9604 upregulates SOX9 transcription factor expression, driving aggrecan and type II collagen synthesis. This chondrogenic pathway is distinct from the metabolic effects and underlies the peptide's potential in osteoarthritis treatment.
Dosage Information
Calculation Results
Syringe Fill Level (100u syringe)
Protocols
AOD-9604 Fat Loss StackIntermediate⚖️Weight Loss20-30 days
Research peptide for targeted fat loss without affecting blood sugar. Can be stacked with other protocols.
Warning: Research peptide. Not FDA approved. Minimal side effects reported.
Stability & Storage
AOD-9604 is supplied as a lyophilized white powder. Store at -20°C for long-term stability (18-24 months) or 2-8°C for up to 6 months. Protect from light and moisture.
The peptide contains a disulfide bond between the two cysteine residues (Cys182 and Cys189 of the native hGH sequence) that is critical for biological activity. Reducing conditions or excessive heat can disrupt this bond, inactivating the peptide.
Reconstitute with bacteriostatic water. The solution should be clear and colorless. Store reconstituted AOD-9604 at 2-8°C and use within 21-28 days. Avoid alkaline pH conditions which may promote disulfide bond rearrangement. The peptide is moderately susceptible to proteolytic degradation, with an in-vivo half-life of approximately 30-45 minutes.
Side Effects & Precautions
Generally Well-Tolerated
Clinical trials demonstrated an excellent safety profile with adverse event rates similar to placebo. AOD-9604 was specifically designed to avoid the side effects of full-length growth hormone.
No Insulin Resistance
Unlike full-length GH and GH secretagogues, AOD-9604 does not impair glucose metabolism or insulin sensitivity. Blood glucose and insulin levels remain stable during treatment.
No IGF-1 Elevation
AOD-9604 does not raise IGF-1 levels, eliminating concerns about growth promotion, acromegalic effects, or potential cancer risk associated with sustained IGF-1 elevation.
Injection Site Reactions
Mild local reactions (pain, redness) at injection sites have been reported. Subcutaneous injection in abdominal tissue is the typical route.
Headache
Mild headache has been reported in some clinical trial participants, though rates did not significantly differ from placebo.
Hypersensitivity
Rare allergic reactions are possible, as with any injectable peptide. Individuals with known sensitivity to hGH-derived products should exercise caution.
No Fluid Retention
Unlike growth hormone, AOD-9604 does not cause significant water retention or edema — consistent with its lack of GH receptor activation.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Regulatory Status
AOD-9604 has a complex regulatory history. It was granted FDA GRAS (Generally Recognized As Safe) status for use as a food ingredient in 2017. The Australian TGA (Therapeutic Goods Administration) has approved AOD-9604 for certain therapeutic applications, including as an intra-articular injection for osteoarthritis.
The peptide did not receive FDA approval for obesity following Phase 3 clinical trials that did not meet the primary weight loss endpoint. However, its GRAS designation establishes its safety profile for oral consumption.
WADA prohibits AOD-9604 under category S0 (Non-Approved Substances) of the prohibited list. Notable doping cases in Australian Football League (AFL) involved AOD-9604 use. The peptide is banned in competition and out of competition for athletes under WADA jurisdiction.
Research Studies
AOD9604: A Novel Lipolytic Peptide Fragment of Human Growth Hormone
Ng FM, Sun J, Sharma L, et al.
Phase 2 Clinical Trial of AOD9604 for Obesity
Stier CT, Ng FM, Herington AC.
The Lipolytic Effect of Growth Hormone Resides in the C-Terminal Fragment
Heffernan MA, Jiang WJ, Thorburn AW, Ng FM.
AOD9604 Stimulates Proteoglycan Production in Cartilage
Metabolic Pharmaceuticals Research.
