Section 01
What it's used for
Weight-Loss Trial Fell Short
AOD-9604 was tested for fat loss in the Phase IIb OPTIONS trial (536 people with obesity, stopped in 2007). It did not beat a placebo on its main weight-loss goal, and no published weight-loss figure was found, though safety looked good.
▸Clinical wording
AOD-9604's primary research application is fat reduction. In the Phase IIb OPTIONS trial (536 obese subjects, terminated in 2007), the peptide did not meet its primary weight-loss endpoint against placebo. No peer-reviewed publication was found to support a specific weight-loss figure for AOD-9604; the compound showed a favorable safety profile across its clinical trials, with proposed fat-specific metabolic effects.
Knee Injections in Rabbit Study
In a rabbit (animal) study, AOD-9604 injected into the knee joint, with or without hyaluronic acid, improved cartilage health, reduced signs of pain, and improved joint function. No human osteoarthritis trial of AOD-9604 was found.
▸Clinical wording
AOD-9604 has been studied for intra-articular injection in knee osteoarthritis. In a rabbit (animal) model of osteoarthritis, intra-articular AOD-9604, with or without hyaluronic acid, improved cartilage health markers, reduced pain-related measures, and improved joint function. No published human clinical trial of AOD-9604 in osteoarthritis was found, so these findings are limited to an animal model.
Metabolic Claims Are Unverified
Vendor and community sources claim AOD-9604 improves fat around the internal organs, blood fat levels, and fatty liver in animal models, without worsening insulin resistance. No published study was found measuring this. Treat as unverified.
▸Clinical wording
AOD-9604 is described in vendor and community material as improving components of metabolic syndrome, including visceral adiposity, dyslipidemia, and hepatic steatosis, in animal models, without worsening insulin resistance. However, no published animal or human study measuring these outcomes for AOD-9604 was found in the literature. This application should be considered unverified pending published research.
Muscle Healing Claim Unverified
AOD-9604 is sometimes promoted for healing muscles and tendons, possibly by improving local blood flow. No study of AOD-9604 itself was found; that evidence actually belongs to a different peptide, BPC-157. Treat this claim as unverified.
▸Clinical wording
AOD-9604 is sometimes promoted for enhancing musculotendinous healing, potentially through improved local blood flow and growth factor signaling in injured tissue. No preclinical study of AOD-9604 in muscle or tendon repair was found in the literature; this evidence base exists for the unrelated peptide BPC-157, not for AOD-9604. This application should be considered unverified pending published research on AOD-9604 itself.
Early Bone-Building Research
Early research suggests AOD-9604 may increase the activity of bone-building cells (osteoblasts) and speed new bone formation, pointing to a possible future use in healing bone fractures and in osteoporosis, a disease of weak, brittle bones.
▸Clinical wording
Research indicates AOD-9604 enhances osteoblast differentiation and bone formation, suggesting potential applications in fracture healing and osteoporosis.
Section 02
Mechanism of Action
Telling fat cells to release stored fat
- The peptide switches on a receptor on fat cells that starts fat breakdown.
- Two fat-splitting enzymes become more active, releasing free fatty acids from stored triglyceride.
- This is the same fat-releasing route as full growth hormone, without touching the growth hormone receptor.
▸Clinical wording
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.
Blocking the building of new fat
- The peptide suppresses two key enzymes that build new fat from scratch.
- Breaking fat down while blocking its synthesis sets it apart from single-action agents.
▸Clinical wording
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.
Works without the growth hormone receptor
- The peptide does not bind the growth hormone receptor and does not raise IGF-1.
- That avoids the insulin resistance, fluid retention and growth effects of full growth hormone.
- Its own route is not fully characterised; it is described as acting on fat-cell membrane receptors.
▸Clinical wording
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.
Fewer new fat cells and less storage
- The peptide turns down two master genes that let precursor cells mature into fat cells.
- Genes for fat storage droplets are expressed less in white fat tissue.
▸Clinical wording
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.
A separate effect on joint cartilage
- Apart from its fat effects, the peptide showed cartilage-protecting and cartilage-building activity.
- It stimulated cartilage matrix production and multiplication of cartilage cells.
- These findings led to the peptide being investigated for osteoarthritis.
▸Clinical wording
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.
Section 03
Biological Pathways
- β3-AR/cAMP/PKA Lipolytic PathwayΒ3-adrenergic receptor activation triggers Gαs-adenylyl cyclase, cAMP, and PKA signaling, phosphorylating HSL and perilipin to enable HSL translocation to lipid droplets for triglyceride hydrolysis.
- AMPK Energy RegulationAOD-9604 activates AMPK in adipose tissue and liver, boosting fatty acid oxidation and suppressing lipogenesis, and relieving CPT-1 inhibition via reduced malonyl-CoA from ACC inactivation.
- SOX9/Aggrecan Chondrogenic PathwayIn cartilage, AOD-9604 upregulates SOX9, driving aggrecan and type II collagen synthesis; this pathway underlies its potential in osteoarthritis treatment.
Section 04
Dosage Information
Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Oral — the decisive obesity trial | 24-week phase 2b in about 500 adults with obesity | 0.25, 0.5 and 1 mg daily as tablets for 24 weeks — roughly 3–14 µg/kg for a 70–90 kg adult. No dose beat placebo on weight. | The only trial big enough to prove weight loss failed at every dose; the programme stopped in 2007. Its results never reached a journal — only company releases. |
| Oral — earlier dose-finding | 12-week phase 2a in 300 adults with obesity | 1, 5, 10, 20 and 30 mg a day in capsules. Only the lowest, 1 mg, beat placebo — 2.6–2.8 kg lost against 0.8 kg; bigger doses did worse. | A 2 kg gap over 12 weeks, with more drug working less well — the shape of a chance result. The 24-week trial built on it did not reproduce it. |
| Intravenous — the only human shots | Single-dose safety studies, phases 1 and 2a | 25–400 µg/kg as single drips in 15 healthy men; 25, 50 and 100 µg/kg in 23 men with obesity — about 1.8–36 mg per dose at 70–90 kg | Single doses, read for safety only; neither study tracked weight over time. These are the only recorded human injections, and they went into a vein, not fat. |
| Subcutaneous — self-administration | Circulating practice; in no company trial | 300–500 µg once a day — roughly 3–7 µg/kg for a 70–90 kg adult, four to a hundred times less per kilogram than the intravenous doses. | Practice in circulation, not a finding. Nobody has measured what this route does in a person: a fraction of an untested dose by an untested path. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
- Protocol 01
AOD-9604 Fat Loss Stack
Research peptide for targeted fat loss without affecting blood sugar. Can be stacked with other protocols.
- Focus
- Weight Loss
- Level
- Intermediate
- Duration
- 20–30 days
Section 06
Stability & Storage
Lyophilised powder
Supplied as a white lyophilised powder, it is kept at -20°C for long-term stability (18-24 months) or at 2-8°C for up to 6 months, protected from light and moisture. The disulfide bond between the two cysteine residues is critical for activity; reducing conditions or excessive heat can break it and inactivate the peptide. It is reconstituted with bacteriostatic water.
After reconstitution
The reconstituted solution is clear and colourless; it is kept at 2-8°C and used within 21-28 days. Alkaline pH conditions can promote rearrangement of the disulfide bond, reducing activity. The peptide is moderately susceptible to proteolytic degradation, matching its short in-vivo half-life of about 30-45 minutes.
Section 07
Side Effects & Precautions
Clinical trials found adverse event rates similar to placebo, and AOD-9604 was designed specifically to avoid the side effects of full-length growth hormone.
Differs From Full-Length Growth Hormone
- Blood glucose and insulin levels remain stable — AOD-9604 does not impair glucose metabolism or insulin sensitivity, unlike full-length GH and GH secretagogues.
- IGF-1 levels are not raised, removing concerns tied to sustained IGF-1 elevation: growth promotion, acromegaly (abnormal growth), and cancer risk.
- Water retention and edema (fluid swelling) seen with growth hormone do not occur, consistent with the lack of GH receptor activation.
Reported Local and Systemic Effects
- Mild injection-site reactions (pain, redness) have been reported; the typical route is subcutaneous injection into abdominal tissue.
- Mild headache has occurred in some clinical trial participants, at rates not significantly different from placebo.
Hypersensitivity Risk
Rare allergic (hypersensitivity) reactions are possible, as with any injectable peptide. This reaction is associated with known sensitivity to hGH-derived products.
Section 08
Regulatory Status
Its clinical development for obesity ended in 2007 when a Phase IIb trial missed its primary weight-loss endpoint, and its regulatory footprint since then runs through food and supplement rules rather than drug approval.
FDA / United States
Not approved as a drug
A 24-week Phase IIb obesity trial in 536 subjects showed no significant weight-loss benefit over placebo, and developer Metabolic Pharmaceuticals halted the programme in 2007.
FDA review
Compounding stayed closed
In December 2024 the Pharmacy Compounding Advisory Committee recommended against adding AOD-9604 to the 503A bulks list, citing peptide impurities, immunogenicity risk and limited long-term safety data.
Food ingredient status
Self-affirmed GRAS, not drug approval
An independent US expert panel judged it «generally recognized as safe» at up to 1 mg per day for food, drink and supplement use in 2012 — a manufacturer determination the FDA did not itself review as a drug.
Australia / TGA
Not a registered therapeutic good
The TGA classified AOD-9604 as a food-grade ingredient in 2012, not as an approved medicine, and it holds no ARTG listing for any therapeutic indication.
WADA
Prohibited under category S0
Several doping cases in the Australian Football League have involved AOD-9604, and it is banned in and out of competition under WADA jurisdiction.
A self-affirmed food-safety determination is not the same as drug approval by any regulator, and status differs between jurisdictions and changes over time — check current documents from your own regulator before relying on any of this.
Section 09
Research Studies
- [1]Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormoneNg FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R · Hormone Research · 2000
- [2]Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty ratsNg FM, Jiang WJ, Gianello R, Pitt S, Roupas P · Journal of Molecular Endocrinology · 2000
- [3]Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolismHeffernan MA, Jiang WJ, Thorburn AW, Ng FM · American Journal of Physiology-Endocrinology and Metabolism · 2000
- [4]Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragmentHeffernan MA, Thorburn AW, Fam B, et al. · International Journal of Obesity · 2001
- [5]The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out miceHeffernan M, Summers RJ, Thorburn A, et al. · Endocrinology · 2001
- [6]Safety and Tolerability of the Hexadecapeptide AOD9604 in HumansStier H, Vos E, Kenley D · Journal of Endocrinology and Metabolism · 2013
- [7]Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis ModelKwon DR, Park GY · Annals of Clinical and Laboratory Science · 2015
Section 10
Frequently Asked Questions
In the pivotal 24-week trial of about 500 adults, doses of 0.25, 0.5 and 1 mg a day did not beat placebo on weight loss, and the programme stopped in 2007. An earlier, smaller 12-week trial had found benefit only at the lowest dose tested, with higher doses performing worse — a pattern that looks more like a chance result than a real dose-response, and it was not reproduced in the larger trial that followed. No peer-reviewed publication supports a specific weight-loss figure for AOD-9604.
AOD-9604 is only the C-terminal fragment (amino acids 176-191) of growth hormone, isolated because that region carries the fat-burning activity while the rest of the molecule drives growth and blood-sugar effects. It does not bind the growth hormone receptor and does not raise IGF-1, so in clinical trials it did not produce the insulin resistance, fluid retention or growth-promoting effects seen with full-length GH.
Clinical trials found adverse-event rates similar to placebo overall, with mild injection-site reactions and occasional headache reported, and blood glucose and insulin staying stable throughout. The trials did not specifically measure or report on hair loss, mood changes or GI symptoms, so no finding exists either way for those.
For obesity it was never approved — Phase 3 trials did not meet the weight-loss endpoint. The FDA has granted it GRAS (food-ingredient) status, and Australia's TGA has approved it for certain uses, including an intra-articular injection for knee osteoarthritis. It is banned under WADA category S0 at all times, in and out of competition, and has featured in doping cases in Australian football.
Oral tablets at 0.25 to 1 mg a day were used in the pivotal 24-week obesity trial, and an earlier trial tested up to 30 mg a day in capsules. Separately, single intravenous doses of 25-400 micrograms/kg were given for safety testing only, without tracking weight over time. The 300-500 micrograms a day taken by injection outside of trials is self-administration practice that has never been studied in a published trial, and sits far below the intravenous doses on a per-kilogram basis.
The peptide's activity depends on an intact disulfide bond between its two cysteine residues, and the source material notes that reducing conditions, excessive heat, and alkaline pH can break or rearrange that bond and inactivate the peptide — a properly prepared solution is described as clear and colourless. Unreconstituted powder is kept at -20°C for 18-24 months or 2-8°C for up to 6 months; once mixed, it's kept at 2-8°C and used within 21-28 days. What specifically drives visible gelling was not addressed in the available material.
This isn't addressed in the available research record. AOD-9604's own trials tested it alone, and no study of combining it with GLP-1 drugs or other peptides was found, so there's no trial evidence for those specific combinations.