AOD-9604

AOD-9604 is a lab made chain of sixteen amino acids, the small building blocks that proteins are made from. Short chains like this are called peptides. Fifteen of them are the tail end of human growth hormone, the stretch numbered 177 to 191, with one more building block called tyrosine added at the front. The group at Monash that had worked on that tail of the hormone built it, and a company called Metabolic Pharmaceuticals funded six trials on it as an obesity drug, roughly 900 people between them, the last one large enough to answer the question. It did not beat the dummy capsule. The company read its own result and closed the obesity programme in February 2007, and it has been sold ever since.

The claim is that it strips fat without the blood sugar trouble that comes with growth hormone itself. The founding result is in animals: Ng and colleagues in 2000 gave obese Zucker rats 500 micrograms per kilogram of rat by mouth every day for 19 days, and weight gain more than halved, 15.8 grams against 35.6 grams in the untreated rats, with no harm to insulin sensitivity. What has not turned up in anything published since is a target. Heffernan and colleagues found in 2001 that it neither latched onto the growth hormone receptor nor made those cells multiply, and that its fat releasing effect does not run directly through the beta-3 adrenergic receptor either, the docking point fat burning drugs usually use. FDA's pharmacology reviewers wrote in 2024 that the molecular targets and mechanisms of action remain unknown. Worth keeping straight what the oldest work even showed: the plain unmodified tail was antilipogenic, which means it blocks fat being made, not that it burns off fat already there.

People buy it for fat loss. A second strand of the marketing is about joints and cartilage, and that one rests on a single rabbit study, 0.25 mg injected into a knee. Neither is what the human record measured: the trials measured weight, by mouth or into a vein, and the largest one did not beat placebo.

Two words carry the sales copy and neither means what it looks like. The first is GRAS, which stands for generally recognised as safe. That is a food ingredient status, not a drug approval, and this one was self-affirmed, meaning the company's own expert panel reached the conclusion, about up to 1 mg a day in food, and never asked the regulator to look. I searched FDA's GRAS Notice Inventory for AOD9604 and it returned zero records. The second is the hyphen. FDA writes the name AOD 9604, a space and no hyphen, which is the likeliest reason a search for the hyphenated name misses the warning letter it sent to a compounding pharmacy on 1 April 2020.

The safety record is small and all of it belongs to one sponsor. In the 12 week oral study in 300 adults, five subjects had serious adverse events and every one of them was a cancer or a tumour. The investigators called none of them related, and FDA found that insufficient. In the intravenous trial in 23 men with obesity, one severe chest tightness was judged possibly related, and five men reported euphoria against none on the dummy treatment. For the route it is actually sold by I could find no published human safety data at all, so the empty record there means unlooked at rather than clean.