AOD-9604 did what it was designed to do in animals and failed where it mattered in humans. It separated growth hormone’s fat-burning effect from its effects on glucose and IGF-1, then produced under 1 kg of drug-attributable weight loss in a 536-patient trial. Its developer ended the obesity program in 2007, and an FDA advisory committee voted 0 to 12 against listing it for compounding.
Key points
- AOD-9604 corresponds to residues 177-191 of hGH with an additional tyrosine at the N-terminus [1].
- In obese mice it reduced weight gain and increased fat oxidation without binding the GH receptor or causing hyperglycemia [2].
- In six randomized placebo-controlled trials it did not change IGF-1 or glucose tolerance, and its tolerability profile was similar to placebo [6].
- In the OPTIONS trial (536 adults), drug-attributable weight loss was under 1 kg in every dose group and the obesity program was terminated in 2007 [8].
- The FDA proposed not adding it to the 503A list and the advisory committee voted 0 to 12 in December 2024 [9].
US status (October 2026): Not FDA-approved, no 503A or 503B compounding pathway, and MDside providers do not prescribe it. See the AOD-9604 status page.
AOD-9604 is a fragment of growth hormone
Human growth hormone (hGH) has well-known lipolytic effects, but long-term use is associated with insulin resistance and hyperglycemia [7]. At Monash University, Frank Ng’s group proposed that the action on fat resided in a specific region of the molecule [4]. The result was AOD-9604: the C-terminal fragment of hGH (amino acids 177-191) with an additional tyrosine at the N-terminus [1], a 16-amino-acid peptide with a disulfide bridge [7]. The Australian company Metabolic Pharmaceuticals developed it as an oral anti-obesity candidate [7].
It does not stimulate the pituitary. That is a different group of compounds, covered in CJC-1295, ipamorelin and MK-677.
The laboratory data were promising
In obese ob/ob mice treated for 14 days with osmotic minipumps, both hGH and AOD-9604 significantly reduced weight gain, with increased fat oxidation and plasma glycerol, an index of lipolysis. Unlike hGH, AOD-9604 did not induce hyperglycemia or reduce insulin secretion, did not compete for the GH receptor and did not induce cell proliferation [2]. A second study linked the effect to increased expression of the β3-adrenergic receptor, although it concluded that the lipolytic action is not mediated directly through that receptor [3].
The oral route was also tested in rodents. In obese Zucker rats, oral treatment for 19 days reduced weight gain by more than 50% (15.8 vs 35.6 g), with no adverse effect on insulin sensitivity measured by euglycemic clamp [4]. In isolated adipose tissue from obese rodents and humans, a related synthetic fragment from the same group, named AOD-9401 in that paper, increased lipolysis and reduced lipogenesis in vitro. Given orally, it reduced weight gain in ob/ob mice [5].
- 16: amino acids, hGH 177-191 plus an N-terminal tyrosine [1][7]
- More than 50%: less weight gain in obese Zucker rats on oral AOD-9604 [4]
- 536: adults enrolled in the phase 2b trial that ended the program [8]
Human safety is the strongest part of the record
The best clinical evidence for AOD-9604 is on safety. Stier and colleagues summarized six randomized, double-blind, placebo-controlled trials, with particular attention to the unwanted effects of hGH: raised IGF-1, insulin resistance and glucose intolerance. AOD-9604 did not change serum IGF-1, the oral glucose tolerance test showed no negative effect on carbohydrate metabolism, and no anti-AOD-9604 antibodies were detected in the patients tested. The authors described a safety and tolerability profile “indistinguishable from placebo” [6].
According to the FDA’s summary, the two largest trials enrolled 300 and 502 participants with obesity, treated orally for 12 and 24 weeks. In the 300-person trial, five participants had serious adverse events, including skin cancers (basal cell carcinoma, squamous cell carcinoma and melanoma) and breast cancer, which the trial’s lead physician did not consider related to the drug. The FDA stated concern about those cancer reports [7]. It also noted that the authors were employees or consultants of the company that funded the trials [7].
The OPTIONS trial ended the obesity program
A first phase 2b trial, without a formal diet and exercise program, showed greater mean weight loss than placebo in all five dose groups at 12 weeks. The best dose (1 mg) missed significance on the primary analysis (p = 0.1), though it reached it in the female subgroup [8]. The OPTIONS trial set out to confirm this: 536 adults, BMI 30 to 45 kg/m², oral doses of 0.25, 0.5 or 1 mg daily or placebo for 24 weeks, with dietitian-supervised diet and exercise, powered to detect a 1.8 kg difference [8].
On February 21, 2007 the company announced that weight loss, after allowing for the diet and exercise program, was under 1 kg in every dose group at 12 and 24 weeks, and that development for obesity was terminated. In the same announcement it described safety and tolerability as excellent, with no difference from placebo [8]. According to the FDA, these results do not appear to have been published in medical journals [7].
Cartilage and bone remain a preclinical line
After closing the obesity program, the company announced it would continue studying AOD-9604 in osteoporosis on the basis of animal results [8]. In cartilage, the most cited published data come from a collagenase-induced knee osteoarthritis model in 32 rabbits. Weekly intra-articular AOD-9604 injections were associated with better morphological and histopathological scores than saline, and the combination with hyaluronic acid was more effective than either treatment alone, with a shorter lameness period [11]. There are no published clinical trials in osteoarthritis, and the FDA did not evaluate that use because the nomination lacked information [7].
The FDA found no evidence of efficacy by any route
In its briefing document for the December 2024 Pharmacy Compounding Advisory Committee, the FDA concluded that evidence of efficacy in obesity by any route is lacking. It found no human data by the subcutaneous or transdermal routes and no human pharmacokinetic studies [7]. In the nonclinical review it noted dose-dependent changes in osteocalcin in rats treated for 26 weeks, minimal periportal vacuolation in monkeys treated for 9 months, and equivocal genotoxicity results [7]. A search of the FAERS adverse event database retrieved no reports [7]. The committee voted 0 to 12 on adding it to the 503A list [9]. The FDA’s Category 2 page lists it among nominations withdrawn by their nominators [10]. The context of the 2026 votes on other peptides is in What the FDA actually said.
That vote matters for your sourcing. With no compounding pathway, the only AOD-9604 on the US market is sold outside the drug supply chain. The research-use-only peptides guide explains why that label does not make a product lawful for patients.
In sport. WADA’s 2026 list includes growth hormone fragments under S2.2.3, “e.g. AOD-9604 and hGH 176-191”, prohibited at all times [12]. A validated urine detection method exists with a limit of 50 pg/mL [1], and the peptide does not interfere with WADA’s hGH isoform immunoassay [13].
The evidence ends at weight loss
AOD-9604 fulfilled part of its design hypothesis. In animals it separated GH’s lipolytic effect from its effects on the receptor, glucose and cell proliferation [2], and in humans it did not raise IGF-1 or alter glucose tolerance [6]. What it did not show was clinically useful weight loss in a large trial with diet and exercise [8]. The safety data come from the oral and intravenous routes, were published in summary form by company-affiliated authors, and do not cover the subcutaneous route [6][7]. The compound remains of scientific interest for the biology of GH fragments and in cartilage models [3][11].
If a patient asks for it, the honest answer is short: the one large trial was negative, the injectable route was never studied in humans, and there is no lawful US source. For approved weight-loss options, see weight management programs.
References
- Cox HD, et al. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015;7(1):31-8. PMID 25208511. Link
- Heffernan MA, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001;25(10):1442-9. PMID 11673763. Link
- Heffernan M, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001;142(12):5182-9. PMID 11713213. Link
- Ng FM, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-8. PMID 11146367. Link
- Heffernan MA, et al. Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. Am J Physiol Endocrinol Metab. 2000;279(3):E501-7. PMID 10950816. Link
- Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J Endocrinol Metab. 2013;3(1-2):7-15. Link
- U.S. Food and Drug Administration. PCAC December 4, 2024 briefing document: AOD-9604-related bulk drug substances. Link
- Metabolic Pharmaceuticals Limited. Metabolic’s obesity drug – Phase 2B clinical trial results (ASX announcement, 21 February 2007), as filed with the SEC. Link
- U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee, December 4, 2024: final meeting minutes. Link
- U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (content current as of 22 April 2026). Link
- Kwon DR, Park GY. Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model. Ann Clin Lab Sci. 2015;45(4):426-32. PMID 26275694. Link
- World Anti-Doping Agency. 2026 Prohibited List, English text as published in Tractatenblad van het Koninkrijk der Nederlanden 2026, Nr. 25. Link
- Orlovius AK, et al. AOD-9604 does not influence the WADA hGH isoform immunoassay. Drug Test Anal. 2013;5(11-12):850-2. PMID 24124033. Link
This is general information, not medical or legal advice. Rules vary by state and change. Confirm your own facts with counsel.