AOD-9604 (Anti-Obesity Drug
9604)

1980s-1995

The GH Fragment Hypothesis

Separating Fat Burning from Growth

Growth hormone does many things: it burns fat, builds muscle, grows bones, and affects glucose metabolism. These effects come from different parts of the large GH molecule and different downstream pathways.

Researchers noticed that certain fragments of GH had specific effects. The C-terminal region — the tail end of the molecule — seemed particularly important for fat metabolism. What if you could use just this fragment?

In Australia, scientists began systematic studies of GH fragments. They found that the region from amino acid 177 to 191 could stimulate lipolysis (fat breakdown) without the growth effects. This fragment didn't raise IGF-1 and didn't affect glucose the way full GH did.

1995-2000

Creating AOD-9604

From Fragment to Drug Candidate

Metabolic Pharmaceuticals took the GH 177-191 fragment and made a small modification — changing the C-terminus to make it more stable. The result was AOD-9604: Anti-Obesity Drug 9604.

Animal studies were promising. Obese mice and rats on AOD-9604 lost weight and increased fat oxidation. The compound appeared to work through beta-3 adrenergic receptors, stimulating fat cells to release and burn their contents.

Importantly, AOD-9604 didn't raise IGF-1 levels or cause the diabetogenic effects of growth hormone. It seemed to be a clean fat-burning agent. Metabolic moved toward human trials.

2000-2007

The Clinical Journey

Trials and Tribulations

Human trials began. Phase I showed safety — no serious adverse effects, no GH-like side effects. The peptide was well-tolerated. Phase II trials began in earnest.

Results were mixed. A 12-week trial showed subjects on AOD-9604 lost 1.8 kg more than placebo — statistically significant but modest. Larger trials aimed to confirm and extend this finding.

The critical Phase IIb trial enrolled 536 subjects for 24 weeks. The results were disappointing: AOD-9604 failed to show statistically significant weight loss over placebo. The primary endpoint was missed. In 2007, Metabolic announced it was discontinuing obesity development.

2007-2015

Pivot to New Applications

Cartilage and Beyond

Though it failed for obesity, AOD-9604 wasn't finished. Researchers noticed the peptide had effects on cartilage and bone repair. A pivot began toward osteoarthritis and joint health.

Studies suggested AOD-9604 could stimulate cartilage regeneration and reduce joint inflammation. While not as dramatic as weight loss claims, these effects opened new potential applications.

The peptide also entered the food supplement space. In 2015, AOD-9604 received FDA GRAS (Generally Recognized As Safe) status as a food ingredient. It began appearing in weight management and joint health supplements.

2015-Present

The Continuing Story

Research Peptide and Beyond

AOD-9604 occupies a unique space. It's one of the few peptides with extensive human safety data (900+ subjects), FDA GRAS status, and yet it never became an approved drug.

It remains popular in the research peptide community, often used for body composition goals. Some clinics offer it for weight management and joint health, though evidence for efficacy remains limited.

The compound's story reflects the challenges of obesity drug development. Even safe, mechanistically sound drugs can fail if effects are too modest. As GLP-1 drugs achieve 15-20% weight loss, the bar for new obesity treatments has risen dramatically.