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Limited Human Evidence

AOD-9604

A 16-amino-acid C-terminal fragment of human growth hormone studied for fat metabolism, with disappointing weight-loss outcomes in humans.

In plain English

AOD-9604 (Anti-Obesity Drug 9604) is a synthetic peptide corresponding to amino acids 176–191 of human growth hormone, with a tyrosine added at the N-terminus. In rodents, it stimulated lipolysis without the diabetogenic effects of full-length GH. Multiple Phase 2 trials in humans failed to show meaningful weight loss compared with placebo, and the originator discontinued development as a weight-loss drug. AOD-9604 has Generally Recognized as Safe (GRAS) status as a food ingredient and is permitted in cosmetic use in some jurisdictions, but it is not an approved drug.

What it is

AOD-9604 is a modified C-terminal fragment of human growth hormone (amino acids 176–191) with an added N-terminal tyrosine.

Mechanism (summary)

Preclinical work suggested fat-mobilizing activity via beta-3 adrenergic receptors and uncoupling protein modulation without acting at the GH receptor. Human data have not borne out these effects clinically.

Why people research it

  • Body-fat reduction without GH-receptor activation
  • Visceral adiposity
  • Osteoarthritis (more recent academic interest)

Human evidence

Two large Phase 2 trials in obesity (n>500 each) failed to show meaningful weight loss vs. placebo. AOD-9604 has GRAS status (FDA Notice No. GRN 000727) for use as a food ingredient.

Animal / lab evidence

Rodent studies showed reductions in body fat and increased fat oxidation without the diabetogenic effects of full-length GH.

Key studies

Each summary explains the design, what was found, and what it doesn't prove.

Human RCT2006·Adults with obesity
Effect of AOD9604 on body composition and metabolism in obese adults (Phase 2)

In a 12-week trial, AOD-9604 did not help adults with obesity lose meaningfully more weight than placebo did.

Finding: Weight loss with AOD-9604 was not significantly greater than placebo over 12 weeks of treatment.
Limitations: Phase 2 dose-ranging; subsequent program did not produce a positive Phase 3 signal.
Review2017·Regulatory review
GRAS Notice (GRN) No. 727 — AOD9604

The FDA accepted that AOD-9604 was safe enough to be used as a food ingredient — not the same as approving it as a drug.

Finding: FDA did not object to AOD-9604 GRAS status as a food ingredient at proposed levels of intake.
Limitations: GRAS food-ingredient status is regulatorily distinct from drug approval.

History

Originally developed by Metabolic Pharmaceuticals in Australia. Discontinued as a weight-loss drug after Phase 2 failed to show efficacy.

Important:

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