AOD-9604 (also written AOD 9604 or AOD9604) is a 16-amino-acid synthetic peptide made of residues 177 to 191 of human growth hormone with an extra tyrosine added at the N-terminus, often written Tyr-hGH(177-191) (Cox 2015). It came out of lipid-metabolism work at Monash University in Australia and was developed as an oral obesity drug by Metabolic Pharmaceuticals, which ended the program in 2007 after a phase 2b trial missed its primary weight-loss endpoint (FDA briefing, 2024). Research-grade AOD-9604 5 mg is supplied for laboratory and animal studies only.
Growth hormone is a 191-amino-acid protein of about 22,000 daltons (Norditropin label). In the early 1990s, Frank Ng’s group in the Department of Biochemistry at Monash University reported that a synthetic peptide matching the last 15 residues of hGH (177-191) had antilipogenic activity in rat fat tissue equal to that of intact hGH, although it showed no significant lipolytic effect in that assay (Wu and Ng 1993).
AOD-9604 adds a tyrosine to the N-terminal end of that 15-residue fragment. FDA’s 2024 evaluation describes it as a hexadecapeptide, a synthetic 177-191 fragment of hGH with an additional N-terminal tyrosine, with the two cysteines cyclized into a disulfide bond, and states that it was developed by Metabolic Pharmaceuticals Limited in the late 1990s (FDA briefing, 2024).
AOD-9604 is also sold and discussed as “hGH fragment 176-191.” A 2026 review in Frontiers in Endocrinology notes that because AOD-9604 is hGH(177-191) plus an N-terminal tyrosine, it is “sometimes labelled” hGH 176-191 (Dominikowski 2026). The label is a convention rather than a literal description. In the NCBI reference sequence for human somatotropin, residue 176 of the mature hormone (position 202 in the precursor record) is phenylalanine, not tyrosine (NCBI NP_000506.2). A peptide that truly copied native residues 176-191 would start with Phe. Researchers comparing products or papers should check the actual sequence on the certificate of analysis, not the name.
| Feature | AOD-9604 | “hGH fragment 176-191” (as commonly labelled) | Full-length hGH (somatropin) |
|---|---|---|---|
| Length | 16 residues | 16 residues | 191 residues, about 22 kDa |
| Sequence | Tyr + hGH 177-191, one disulfide bond | Often the same Tyr-initiated sequence; a literal native 176-191 would begin with Phe | Identical to pituitary hGH |
| hGH receptor binding | Did not compete for the hGH receptor or drive receptor-mediated proliferation in vitro | Depends on the actual sequence supplied; not separately studied under this name | Binds dimeric GH receptors |
| IGF-1 | No effect on serum IGF-1 reported in the sponsor’s six-trial summary | No separate data | Induces IGF-1; label notes serum IGF-I may increase |
| Glucose effects | No hyperglycemia in obese mice; no negative effect on carbohydrate metabolism reported in humans | No separate data | Label warns of decreased insulin sensitivity and glucose intolerance |
| Regulatory status | Not approved; development for obesity terminated in 2007 | Not approved | FDA-approved for labeled indications |
Sources for the table: Heffernan 2001a, Stier 2013, FDA briefing 2024, NCBI NP_000506.2 and the Norditropin prescribing information.
Heffernan and colleagues at Monash treated obese (ob/ob) and lean C57BL/6J mice with hGH, AOD-9604 or saline for 14 days using mini-osmotic pumps. Both hGH and AOD-9604 significantly reduced body-weight gain in the obese mice, with higher in vivo fat oxidation and higher plasma glycerol, an index of lipolysis. Unlike hGH, AOD-9604 did not cause hyperglycemia or lower insulin secretion. In cells engineered to express the hGH receptor, AOD-9604 did not compete for receptor binding and did not induce proliferation (Heffernan 2001a).
A second 2001 study looked at how the fat-loss effect might work. After 14 days of treatment, hGH and AOD-9604 both reduced body weight and body fat in obese mice and raised beta-3 adrenergic receptor (beta3-AR) RNA back toward lean-mouse levels. In beta3-AR knockout mice, long-term treatment did not produce the weight change or increase in lipolysis seen in wild-type controls. In an acute experiment, though, AOD-9604 still increased energy expenditure and fat oxidation in the knockouts. The authors concluded that the lipolytic actions are not mediated directly through beta3-AR, even though both compounds increase its expression (Heffernan 2001b).
AOD-9604 is often described as a beta-3 agonist, and the source study does not support that description. FDA’s 2024 review did not describe it as one either. It stated that findings from one study suggest the lipolytic effects depend, at least in part, on beta3-AR signaling, but that the molecular target(s) and mechanism(s) underlying its pharmacological effects remain unknown (FDA briefing, 2024). That reading fits the chronic knockout results above.
Stier and colleagues, who were employees or consultants of the sponsor, summarized six randomized, double-blind, placebo-controlled trials. Two used single intravenous doses in small groups of men; four used oral dosing; the two largest ran 12 weeks (300 participants) and 24 weeks (502 participants). The authors reported a safety and tolerability profile “indistinguishable from placebo,” no effect on serum IGF-1, no negative effect on carbohydrate metabolism, and no anti-AOD-9604 antibodies in the participants tested (Stier 2013).
FDA’s reviewers read the same paper more cautiously. They noted that the trial summaries lacked a detailed breakdown of adverse events, that intravenous studies were small and short, and that the serious adverse events reported by five participants in the 12-week oral study included basal cell carcinoma, squamous cell carcinoma, breast cancer and melanoma, along with a lipoma. The investigators judged these unrelated to treatment, but FDA wrote that the information was insufficient to say whether they were unrelated (FDA briefing, 2024).
Metabolic Pharmaceuticals’ OPTIONS study enrolled 536 adults with obesity (BMI 30 to 45), of whom 502 were randomized to oral AOD-9604 at 0.25, 0.5 or 1 mg once daily or placebo, alongside a dietitian-supervised diet and exercise program, for 24 weeks. The primary endpoint was statistically significant weight loss versus placebo at 12 weeks for any of the three doses; the trial was powered to detect a 1.8 kg difference. There was no significant difference in weight loss between AOD-9604 and placebo. On February 21, 2007, the company announced that the results did not support commercial viability and that development for obesity was terminated (FDA briefing, 2024).
FDA noted that the OPTIONS results were never published in the medical literature and that a search of ClinicalTrials.gov found no AOD-9604 studies. Its overall conclusion was that the available data do not support effectiveness for obesity by any route, and that no human data exist for subcutaneous or transdermal use (FDA briefing, 2024).
Many sources say AOD-9604 has FDA “GRAS” (generally recognized as safe) status as a food ingredient. We could not verify this. FDA’s GRAS Notice Inventory lists the notices filed with the agency since 1998, and a download of the full inventory in September 2026 contained no entry for AOD-9604 or a growth hormone fragment (FDA GRAS Notice Inventory).
In the 2024 compounding review, a nominator’s form listed “USA GRAS Status” but pointed to a 2012 company announcement on the Australian stock exchange, not to an FDA response letter (FDA briefing, 2024). Whatever GRAS conclusion the company reached, there is no FDA GRAS notice on record (FDA GRAS Notice Inventory), and GRAS status for a food use would not make it an approved drug.
FDA prepared an evaluation of AOD-9604 for its Pharmacy Compounding Advisory Committee meeting on December 4, 2024, after it was nominated for weight loss, osteoporosis and osteoarthritis. FDA did not evaluate the osteoporosis and osteoarthritis uses. Its nonclinical review flagged dose-dependent changes in serum osteocalcin in a 26-week rat study, minimal periportal hepatocyte vacuolation in a 9-month monkey study, and equivocal genotoxicity results (FDA briefing, 2024).
The nominations were later withdrawn. FDA’s page on bulk drug substances that may present significant safety risks now lists AOD-9604 under “nominated but withdrawn,” a list of substances previously in category 2 of its interim compounding policies, citing possible immunogenicity for certain routes, peptide-impurity and characterization issues, limited safety information, and serious adverse events whose causality is unclear (FDA, updated April 2026).
The World Anti-Doping Agency’s 2026 Prohibited List names AOD-9604 and hGH 176-191 as examples of prohibited growth hormone fragments, banned at all times (WADA 2026 Prohibited List, S2.2.3). Anti-doping labs have developed urine assays for the peptide and a stable metabolite (Cox 2015).
The cartilage claims trace mainly to one study. Kwon and Park induced knee osteoarthritis in 32 New Zealand white rabbits with collagenase, then gave weekly intra-articular injections of saline, hyaluronic acid (HA), AOD-9604, or AOD-9604 with HA. At 8 weeks, gross and histological cartilage-damage scores were higher in the saline group than in all treated groups, and lowest in the combined AOD-9604 plus HA group. The combination group also had the shortest period of lameness. The authors concluded that AOD-9604 enhanced cartilage regeneration in this model and that the combination worked better than either agent alone (Kwon and Park 2015).
This is a single, small animal study using a chemically induced injury. The 2026 Frontiers review describes osteoarthritis and joint-repair claims as grounded mainly in animal work, without convincing human trial evidence (Dominikowski 2026).
AOD-9604 sits apart from the GH-axis secretagogues. GHRH analogs such as tesamorelin act upstream on the GH-IGF-1 axis (Dominikowski 2026), whereas AOD-9604 was designed to keep a lipid-metabolism signal without engaging the GH receptor. It also differs from centrally acting appetite compounds; our tesofensine research overview covers one example. For sourcing, the guide to purity testing and vendor checks explains how to read HPLC and mass-spectrometry reports, which is the practical way to confirm the Tyr-initiated sequence and the disulfide bond.
Often. AOD-9604 is Tyr plus hGH 177-191, and it is sometimes labelled hGH 176-191 (Dominikowski 2026). Native residue 176 is phenylalanine, so check the sequence on the certificate of analysis.
Not in the trial designed to show it. The largest trial, OPTIONS, did not show a significant weight-loss difference from placebo at its 12-week primary endpoint, and the sponsor terminated obesity development in 2007 (FDA briefing, 2024).
The sponsor’s six-trial safety summary reported no effect on serum IGF-1 (Stier 2013), consistent with cell-based data showing no competition for the hGH receptor (Heffernan 2001a).
No. FDA’s 2024 review concluded that the available data do not support effectiveness for obesity by any route (FDA briefing, 2024). No GRAS notice for it appears in FDA’s inventory (FDA GRAS Notice Inventory), and FDA’s page on bulk drug substances that may present significant safety risks lists it as nominated but withdrawn, meaning it was previously in category 2 (FDA).
Peptides For Sale stocks AOD-9604 as AOD-9604 5 mg and AOD-9604 10 mg lyophilized vials. Both contain the same peptide; the choice depends on how much material a study design needs.
Research use only. All products sold on this site are intended strictly for in vitro laboratory research and preclinical study by qualified professionals. They are not drugs, foods, dietary supplements or cosmetics, are not intended for human or veterinary use, and must not be used to diagnose, treat, cure or prevent any disease. Doses mentioned above are reported only to describe what published studies used, and nothing in this article is medical advice or guidance for personal use.
