HGH Fragment (AOD-9604)

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HGH fragment, also known as AOD-9604, is a synthetic version of HGH (human growth hormone) fragment 176-191. AOD-9604 is a short hexadecapeptide that has been found to promote lipolysis.

Although it is derived from HGH, it does not exert its activity through the same pathway. Instead, it works independently of IGF-1, so it does not raise blood glucose levels or stimulate growth.

Mechanism of Action

The mechanism of action of AOD-9604 has not been fully elucidated, but research has uncovered some information about its workings:

• It does not bind to the growth hormone receptor (GHR): Any binding is outcompeted by the full-length growth hormone. This means that, although it does confer some of the benefits of HGH, its range of activity is narrower and not dependent on GH receptor binding. It has no anabolic or growth-promoting effects [1].
  • It can modulate the beta-3 adrenergic receptor (β3-AR) pathway: It can increase the expression of β3-AR mRNA, a lipolytic receptor, in adipose tissue, increasing energy expenditure and fat oxidation [2].
  • It can inhibit lipogenesis: It has been found to reduce lipogenesis (the synthesis of fat) in animal models [3].

Therapeutic Potential

Research on AOD-9604 has been guided so far by its parent hormone, HGH. As such, it has been researched for several different therapeutic uses for which HGH has also demonstrated promise in:

• Weight loss: Much of the research has focused on the ability of AOD-9604 to promote lipolysis and weight loss. Clinical trials have been conducted to test its efficacy as a drug for treating obesity, with initial trials reporting weight loss in participants. A later trial reported less significant results but also incorporated diet and exercise changes into participants’ treatment [4].
• Joint health: Animal tests have found that, when injected into damaged joints, it significantly improves the speed of healing [5].
• Bone health: It was able to prevent bone loss in animal models of postmenopausal osteoporosis [6].

Safety

Both animal and human studies have found AOD-9604 to be well-tolerated, with no serious adverse events reported.

AOD-9604 may be used as a performance-enhancing drug and is banned by the World Anti-Doping Agency (WADA).

How AOD-9604 Compares To HGH

The HGH Fragment AOD-9604 is a short chain of amino acids that represents a specific domain of the full HGH protein, giving it a narrower range of activity than HGH.

AOD-9604 and HGH both increase fat oxidation and stimulate the breakdown of fat in adipose tissue, promoting weight loss, but they differ in the following ways:

• HGH can cause hyperglycaemia and reduce insulin secretion, while AOD-9604 does not.
• HGH promotes the growth of muscle and bone tissues, while AOD-9604 does not. It may, however, help to prevent hormone-driven bone loss.

Data Sheet

• Application: Research on lipolysis, joints, and bone health.
• CAS Number: 221231-10-3
• Molecular Weight: 1815.1
• Sequence: YLRIVQCRSVEGSCGF
• Chemical Formula: C₇₈H₁₂₃N₂₃O₂₃S₂
• Synonyms: AOD9604, AOD 9604
• Storage: Keep refrigerated at 2-8°C until use. Store it at a temperature of -20°C for long-term storage.
• Reconstitution: Reconstitute in sterile water. The reconstituted solution is stable for up to 30 days at 2-8°C.
• Organoleptic Profile: White to off-white lyophilised powder
• Physical Form: Solid

Conclusion

AOD-9604 is a synthetic version of fragment 176-191 of HGH. Since it does not bind to typical GH receptors, it avoids the systemic effects associated with GH. The exact mechanism by which it works is not fully understood, but we know that it stimulates lipolysis by upregulating β3-AR.

It may also be useful for the treatment of other health conditions, such as joint problems and osteoporosis, but more conclusive evidence from research is required in these areas. Its main benefit over HGH is that it has a much narrower range of effects on the body and does not interfere with carbohydrate metabolism or stimulate growth.

References

1. Stier H, Vos E, Kenley D. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans.
   J Endocrinol Metab. 2013;3(1-2):7-15. doi:10.4021/jem.v3i1-2.157
2. Heffernan M, Summers RJ, Thorburn A, et al. The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice and β
   3-AR Knock-Out Mice. Endocrinology. 2001;142(12):5182-5189. doi:10.1210/endo.142.12.8522
3. Heffernan MA, Jiang WJ, Thorburn AW, Ng FM. Effects of oral administration of a synthetic
   fragment of human growth hormone on lipid metabolism. Am J Physiol-Endocrinol Metab.
   2000;279(3):E501-E507. doi:10.1152/ajpendo.2000.279.3.E501
4. Metabolic Pharmaceuticals Ltd. AOD9604 Phase II Clinical Trial Update. Australian Securities Exchange; 2007. Accessed December 3, 2025. https://www.sec.gov/Archives/edgar/vprr/0702/07021963.pdf
5. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic
   Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015;45(4):426-432