AOD-9604: The One That Got Its Phase 2b, and Missed
502 adults, 24 weeks, three doses against placebo, no separation on the primary endpoint. It is hGH 177-191 with a tyrosine on the front, one oxygen away from the fragment sold as 176-191, and neither of those records is this one's.
What it is, and the molecule sixteen daltons away
AOD-9604 is sixteen amino acids: the fifteen residue tail of human growth hormone, residues 177 to 191, with a tyrosine added at the front. Put a phenylalanine on the front of that same fifteen instead, and you have hGH fragment 176-191. I checked both against UniProt P01241 and PubChem: identical carbon, hydrogen, nitrogen and sulfur counts, one extra oxygen, 1815.1 daltons against 1799.1.
The literature that predates AOD-9604 is on neither of them. It is on the bare unmodified hGH 177-191, from the same Monash group that later built AOD-9604, and Wu and Ng 1993 reported that fragment was antilipogenic in rat fat pads, as active as the intact hormone (PMID 8358331). Antilipogenic means it blocks fat being made, not that it burns off fat already there. The lineage runs 177-191, then AOD-9604. hGH 176-191 is a third compound, and it has its own entry here. Nothing below is evidence for that one, and nothing in that entry is evidence for this one.
The confusion has reached peer review. A Frontiers in Endocrinology review of 18 June 2026 prints the two in its abstract as one compound (PMID 42395176).
What the animals were given
Ng and colleagues 2000 is the founding result. Obese Zucker rats, oral gavage, 500 mcg per kilogram per day for 19 days, and weight gain more than halved, 15.8 g against 35.6 g in controls, with no adverse effect on insulin sensitivity on a euglycemic clamp, unlike intact growth hormone (PMID 11146367). A euglycemic clamp checks insulin is still working.
Nobody has named a target since. Heffernan and colleagues found in 2001 that AOD9604 neither competed for binding nor induced proliferation in cells carrying the growth hormone receptor (PMID 11673763), and that its lipolytic effect does not run directly through the beta-3 adrenergic receptor either (PMID 11713213). So not the receptor its parent hormone uses, and not the one fat burning drugs usually use. FDA's pharmacology reviewers wrote in 2024 that the molecular targets and mechanisms of action remain unknown. The joint and cartilage marketing rests on one rabbit study, 0.25 mg a knee, injected into the joint (PMID 26275694).
What the trials found
Six randomised double-blind placebo-controlled trials were run, METAOD001 through METAOD006, roughly 900 subjects between them, all funded by Metabolic Pharmaceuticals, with the summary paper written by that sponsor's employees and consultants (DOI 10.4021/jem157w).
The first four were small and male, 15 to 36 subjects apiece. The intravenous ones ran 25 to 400 mcg/kg as single doses, then 25, 50 and 100 mcg/kg weekly in 23 men with obesity, where the 0.58 kg lost over three weeks did not separate from placebo, one severe chest tightness was judged possibly related, and five men reported euphoria against none on placebo. The oral ones ran 9, 27 and 54 mg, in 17 men and then in 36.
METAOD005 was the first with a real population. 300 adults with obesity aged 30 to 60, randomised after a two week run-in to oral 1, 5, 10, 20 or 30 mg once daily or placebo, 50 to a group, for 12 weeks. Stier reports no statistically significant changes in any parameter measured. A conference abstract of the same trial claims the largest weight loss at the smallest dose, 0.22 kg per week at 1 mg against 0.07 on placebo, and FDA judged that of unclear therapeutic meaning and could not find the methods published anywhere.
The trial built to settle it
METAOD006 was marketed as the OPTIONS Study. 536 enrolled and 502 randomised, adults 18 to 65 with a BMI of 30 to 45, oral 0.25, 0.5 or 1 mg once daily or placebo alongside a dietician-supervised diet and exercise programme, for 24 weeks. The primary endpoint was statistically significant weight loss at 12 weeks for any one of the three doses, powered for an 80 percent chance of reaching significance if the drug beat placebo by 1.8 kg. Powered means it was built large enough that a gap that size should have shown up. It did not.
Look at those doses against the 12 week study, which ran 1 through 30 mg by mouth. The phase 2b went an order of magnitude down, on the strength of an unpublished claim that the smallest dose worked best.
Development for obesity was terminated on 21 February 2007. FDA adds that the study does not appear to have been published in the medical literature at all, so the primary record for the largest trial ever run on this compound is a stock exchange filing. Go and search ClinicalTrials.gov for it yourself. I queried the v2 API three ways and every one came back zero. Six human trials, none of them on the registry.
A GRAS status FDA never saw
GRAS stands for generally recognised as safe. It is a food ingredient status, not a drug approval. In June 2012 Metabolic Pharmaceuticals, then a subsidiary of the ASX-listed Calzada Limited, announced that AOD9604 had self-affirmed GRAS status, conditional on publication of its existing safety data, for use in foods, drinks and dietary supplements in the United States at up to 1 mg per person per day.
I searched FDA's GRAS Notice Inventory for AOD9604 and it returned zero records. Self-affirmed means a company's own expert panel reached the conclusion and never asked FDA to look, so there is no agency review, no no-questions letter and no entry in the inventory. It is a survey of the house written by the owner selling it.
What the regulators actually did
The 503A bulks list below is what a compounding pharmacy is allowed to make medicines from. The Pharmacy Compounding Advisory Committee took up AOD-9604 free base and its acetate for obesity on 4 December 2024, agreed 12 to 0 to take one vote covering both, then voted on placing them on the 503A bulks list. Twelve no, none yes, none abstaining, and the minutes record no committee discussion on the question. On FDA's own pages, read on 5 August 2026, it appears only under Bulk drug substances nominated but withdrawn.
There is also a warning letter. On 1 April 2020 FDA wrote to Tailor Made Compounding LLC, reference 594743, citing the firm for compounding drug products using AOD 9604 alongside twenty-one other bulk substances including BPC 157, CJC 1295 and Melanotan II, on the grounds that products compounded from them are not eligible for the section 503A exemptions. Note how FDA writes the name. AOD 9604, a space and no hyphen. That spelling is the likeliest reason a search for the hyphenated name misses it.
How it compares
| Approved? | Human trials behind it | What that evidence covers | |
|---|---|---|---|
| AOD-9604 | No. Twelve against, none in favour, at FDA's compounding committee | Six, one sponsor, roughly 900 subjects | Weight, by mouth and into a vein. The one trial powered to find an effect did not find it |
| HGH Fragment 176-191 | No, and never nominated | None, across six searches of four databases | Two rat papers and one cell study. The 1978 one raised blood glucose |
| Semaglutide | Yes, for diabetes and for weight | Past 25,000 people in outcome trials alone | Weight, heart attacks, strokes and kidney decline, all on manufactured product |
Where 300 mcg comes from
Vendor and clinic dosing pages converge on 300 mcg per day by subcutaneous injection into abdominal fat, first thing in the morning on an empty stomach, inside a wider band of roughly 250 to 500 mcg per day, cycled 5 days on and 2 days off in 8 week blocks.
Every human dose in the record is intravenous, 25 to 400 mcg/kg as single doses, or oral, 0.25 mg to 54 mg daily. I ran PubMed searches across every synonym I could construct and found nothing subcutaneous in humans, and FDA searched for the same thing in December 2024 and reported the same nothing. The only subcutaneous administration anywhere in the published record is 250 mcg/kg/day by implanted osmotic minipump in ob/ob mice.
I could not establish a stated derivation for the injectable numbers and I am not going to invent one. What can be observed is a coincidence of magnitude: the phase 2b used 0.25, 0.5 and 1 mg by mouth, and the GRAS level was up to 1 mg a day in food. Carrying an oral number across to an injection is not the cautious move it looks like.
What could go wrong
The safety record is small and it belongs to one sponsor. Five subjects had serious adverse events and every one was a cancer or a tumour. The investigators called none of them related, and FDA found that insufficient. That was the twelve week oral study, in three hundred people.
My take
Most of the compounds in this reference are sold on evidence that was never gathered. This one was gathered, at real expense, and came back negative. 502 people, a supervised diet and exercise programme, a pre-specified endpoint, and the sponsor read its own result and closed the programme in February 2007. Nineteen years on it is still sold, by a route nobody in the published record was given it by.
The word doing the heaviest lifting in the marketing is GRAS, self-affirmed by a panel the sponsor chose. The word doing the second heaviest is the hyphen, which is not marketing at all, just an accident of typing that keeps a 2020 warning letter out of everybody's search results.
If you have seen AOD-9604 sold with GRAS in the copy, did the page say self-affirmed anywhere, or did it just say GRAS?
Frequently asked
Does AOD-9604 work for fat loss?
The largest trial ever run on it says no. It was built to show significance if the drug beat placebo by 1.8 kg, it did not, and the sponsor terminated development for obesity on 21 February 2007.
Is AOD-9604 the same thing as HGH Fragment 176-191?
No. They differ by a single oxygen atom, 1815.1 daltons against 1799.1, and they are two separate compounds with two separate records. The fragment sold as 176-191 has its own entry on this site, and I could not find a human study of it.
Has AOD-9604 ever been studied as an injection under the skin?
I could not find one. Every human dose in the published record went into a vein, at 25 to 400 mcg/kg as single doses, or was swallowed, at 0.25 mg to 54 mg daily, and those are trial doses rather than anything anybody is recommending.
Is AOD-9604 approved, and what does GRAS actually mean here?
It is not approved as a drug anywhere I could find. I searched FDA's GRAS Notice Inventory for AOD9604 and it returned zero records.
What are the side effects of AOD-9604?
In the 12 week oral study in 300 adults, five subjects had serious adverse events and every one was a cancer or a tumour; the investigators called none of them related and FDA found that insufficient. I could find no published safety data for the route it is sold by, injection under the skin.
Why does searching for the FDA warning letter about AOD-9604 turn up nothing?
FDA writes the name with a space and no hyphen, so a search for the hyphenated form misses it.
This content is for educational and informational purposes only and is not medical advice. Peptides discussed are research compounds and may not be approved for human use. Nothing here should be used to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any peptide, supplement, or protocol. Individual responses vary. Do not self-administer compounds without proper medical supervision.
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