AOD-9604
AOD-9604 is unusual in this library: it was tested properly in humans for weight loss, and it did not work. The trial record is the most useful thing about it.
- Legal lane: not FDA-approved. Compounding status has moved repeatedly; check before assuming availability.
- Evidence grade: B for evidence quality, with a negative result
- Form: oral in the trials; sold as an injection
- Also called: hGH fragment 176-191
What it is
AOD-9604 is a modified fragment of the tail end of the human growth hormone molecule, developed by Metabolic Pharmaceuticals in Melbourne. It was designed to trigger the fat-burning part of growth hormone's activity without the rest of it. Notably, it does not bind the growth hormone receptor and does not raise IGF-1, which the trials confirmed.
What the evidence shows
This is the part that matters, and the part marketing tends to skip.
- An earlier, shorter trial reported about 2.6 to 2.8 kg of weight loss on the 1 mg dose against roughly 0.8 kg on placebo. That result is the one quoted on sales pages.
- The pivotal trial was a 24-week, placebo-controlled study in 536 participants, adequately powered to detect weight loss. It did not meet its primary endpoint. There was no significant weight loss against placebo.
- Metabolic Pharmaceuticals ceased development in 2007. The Australian regulator rejected an obesity indication.
- Across the human trials, tolerability was indistinguishable from placebo, with no serious adverse events attributed to the compound.
So: good safety record, well-run trial, negative result. The rodent mechanism did not translate, which researchers attribute to differences between mouse and human fat tissue.
About the GRAS designation
AOD-9604 received GRAS status ("generally recognized as safe") from the FDA for use as an ingredient in certain oral products at specified levels. This is a food-ingredient pathway. It is not a drug approval, it says nothing about whether the compound works, and it does not cover injection. It is the single most misused fact in AOD-9604 marketing.
Legal status
AOD-9604 has never held an FDA-approved indication. Its compounding status has changed several times as nominations were filed and withdrawn and the advisory committee reviewed it. Because this keeps moving, check the FDA's current bulk substances list rather than trusting a vendor's claim about availability.
Reported dosing
The human trials used oral doses of 1 mg, 5 mg, 10 mg and 30 mg daily. The 1 mg dose was the one that performed best in the earlier study. Note that the product sold today is an injection, which these trials did not test.