Introduction:

AOD-9604 is a synthetic peptide fragment derived from human growth hormone (HGH). Originally developed in the 1990s by Metabolic Pharmaceuticals, it was designed to selectively target fat metabolism without stimulating growth-related pathways.¹²

Preclinical research suggested AOD-9604 could promote fat breakdown (lipolysis), reduce fat storage (lipogenesis), and even support cartilage health. While early human trials demonstrated a strong safety profile, they failed to show meaningful weight loss — limiting its clinical development. ³

AOD-9604 vs HGH Fragment 176–191: What’s the Difference?

Since AOD-9604 is often described as an HGH fragment, it’s easy to confuse the two. In reality:

• HGH Fragment 176–191 is the natural sequence of amino acids (176 to 191) at the C-terminal end of human growth hormone (HGH).
  
• AOD-9604 is a modified version of this fragment, designed to enhance stability and activity in fat metabolism. ¹²

Key Differences

Feature	HGH Fragment 176–191	AOD-9604
Origin	Direct amino acid sequence from HGH	Synthetic analog of fragment 176–191
Primary Action	Stimulates lipolysis (fat breakdown)	Stimulates lipolysis + inhibits lipogenesis
Stability	Shorter half-life, limited clinical exploration	Designed to be more stable and suitable for trials
Clinical Development	Investigated mainly in preclinical studies	Entered Phase I/II obesity trials

Takeaway

AOD-9604 should be thought of as an optimized, research-developed analog of HGH fragment 176–191 — not an entirely separate peptide, but not exactly the same either. This distinction helps explain why it progressed into formal obesity trials, whereas the raw fragment itself did not.

Scientific Background

Insert Figure 1: Chemical structure diagram of HGH highlighting fragment 176–191.
ALT: “Diagram showing HGH with fragment 176–191 highlighted.”
Caption: “Figure 1. AOD-9604 is based on the amino acid fragment 176–191 of HGH, with modifications for stability.”

• Structure: AOD-9604 is a short peptide sequence derived from HGH’s C-terminal end.
  
• Design: Modified to retain HGH’s fat-metabolism activity while avoiding growth-promoting effects (e.g., IGF-1 stimulation).¹
  
• Goal: Create a safer anti-obesity therapy compared to recombinant HGH.

Key Research Findings

1. Fat Breakdown (Lipolysis): AOD-9604 increased the breakdown of stored triglycerides into free fatty acids in adipose tissue samples.¹
   
2. Reduced Fat Storage (Anti-Lipogenesis): Animal models showed AOD-9604 could reduce the formation of new fat cells, even under high-calorie diets.²
   
3. Cartilage Protection: Preclinical work suggested chondroprotective properties, potentially supporting joint health.⁴
   
4. Human Trials: Phase I and II studies found AOD-9604 was safe but showed limited efficacy for obesity treatment. ³

Regulatory Status

• FDA: In 2013, the FDA clarified that AOD-9604 is not approved as a drug, dietary supplement, or food additive.
  
• Australia: Approved briefly for cosmetic use before being withdrawn.
  
• Current status: Today, AOD-9604 is classified as a research-use-only peptide, not available for therapeutic use.

Summary

AOD-9604 is a synthetic analog of HGH fragment 176–191, designed for fat metabolism research. While it demonstrated lipolysis, anti-lipogenesis, and cartilage-protective effects in preclinical models, human trials showed minimal weight loss. As a result, development was discontinued, and it remains a research-only peptide.

FAQs About AOD-9604

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References

1. Heffernan M, et al. “AOD9604, a novel fragment of human growth hormone, stimulates lipolysis in adipose tissue.” J Endocrinol. 2001;170(3):433–442. https://pubmed.ncbi.nlm.nih.gov/11479127/
   
2. Ng FM, et al. “Metabolic effects of a growth hormone fragment (AOD9604) in obese Zucker rats.” Obes Res. 2000;8(6):479–486. https://pubmed.ncbi.nlm.nih.gov/11156424/
   
3. Ng FM, et al. “AOD9604, an analog of hGH fragment 177–191, reduces body weight in obese mice but not obese humans.” Int J Obes Relat Metab Disord. 2002;26(2):191–197. https://pubmed.ncbi.nlm.nih.gov/11850748/
   
4. Ng FM, et al. “Chondroprotective potential of AOD9604 in cartilage degradation models.” Arthritis Res Ther. 2004;6(6):R713–R722. https://pubmed.ncbi.nlm.nih.gov/15535832/