Editorial note: this article summarises published research on HGH Fragment 176-191 and AOD-9604. Baclabs does not sell HGH Fragment 176-191, AOD-9604 or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.
HGH Fragment 176-191 and AOD-9604 are marketed as two different fat-loss peptides. They are not. Both names describe the same 16-amino-acid sequence taken from the carboxyl (C-terminal) end of human growth hormone (hGH), and the “176-191” label simply counts the stabilising tyrosine that Metabolic Pharmaceuticals added when it turned an academic fragment into a drug candidate.
The interesting question is what the molecule actually does. In obese mice it mobilises fat without the rise in blood glucose that full-length GH causes. In roughly 900 human trial participants it was as safe as placebo, and about as effective. This article covers both halves of that record and ends with reconstitution maths for a 5 mg vial.
HGH Fragment 176-191 and AOD-9604: one peptide, two names
In the 1990s Frank Ng’s group at Monash University showed that the C-terminal region of hGH, residues 177–191, retained the hormone’s ability to stimulate lipolysis in fat cells while lacking its growth-promoting effects. Their first synthetic version was called AOD9401 (AOD for “anti-obesity drug”). In Zucker fatty rats, AOD9401 stimulated hormone-sensitive lipase, reduced lipogenesis and lowered body weight gain without altering blood glucose [1].
AOD-9604 is that sequence with a tyrosine added at position 176 to improve stability, which makes it hGH 176-191 by numbering. When vendors list “HGH Frag 176-191” and “AOD-9604” as separate products, they are describing the same molecule; any differences are in purity, salt form and fill weight, not pharmacology.
What the rodent lipolysis data showed
The key mouse study is Heffernan and colleagues, published in the International Journal of Obesity in 2001. Obese (ob/ob) and lean C57BL/6J mice received hGH, AOD-9604 or saline by mini-osmotic pump for 14 days. Both hGH and the fragment reduced body-weight gain in the obese animals and increased fat oxidation measured by indirect calorimetry. The difference was in the side effects: hGH raised plasma glucose and insulin, while AOD-9604 did not [2]. In vitro, both compounds increased lipolysis and reduced lipogenesis in isolated adipocytes.
A companion paper in Endocrinology explored mechanism: the fragment’s long-term effects on weight and fat were blunted in beta-3 adrenergic receptor (β3-AR) knockout mice, suggesting the receptor is part of the pathway [3]. Earlier work had reported oral activity in mice, which is why the human trials used tablets.
“Without hyperglycaemia”: what the claim rests on
GH is diabetogenic: it raises blood glucose by opposing insulin action, and it raises insulin-like growth factor 1 (IGF-1), which drives tissue growth. The fragment was designed to keep the lipolytic domain and lose the rest.
The human data support the “no hyperglycaemia” half. In the pooled safety analysis of six trials, AOD-9604 had no effect on serum IGF-1, no adverse effect on carbohydrate metabolism, and did not provoke anti-AOD9604 antibodies [4]. That is a real pharmacological distinction from GH. What the human data do not support is the implied second half, that isolating the lipolytic domain produces meaningful fat loss.
Six human trials, one outcome
Between 2001 and 2006 Metabolic Pharmaceuticals ran six randomised, double-blind, placebo-controlled studies (METAOD001–006) in about 893 adults. Doses ranged from 25 to 400 mcg/kg intravenously in the early studies to 0.25–54 mg/day orally in the later ones, with treatment lasting from a single dose up to 24 weeks [4]. The largest, METAOD006, was a phase 2b study of oral tablets at 0.25, 0.5 or 1 mg daily in 536 obese adults, with weight loss at 12 and 24 weeks as the primary endpoint [5].
The safety paper published in 2013 concludes that the compound was “very well tolerated” with a profile “indistinguishable from placebo”: no withdrawals or serious adverse events attributable to treatment, no antibody formation, no IGF-1 signal [4]. It does not present efficacy data. The phase 2b results announced in 2007 did not show a statistically significant difference from placebo in weight loss, and the company stopped drug development. No efficacy paper from the programme was ever published in a peer-reviewed journal, which is itself informative.
From failed drug to food ingredient
The safety record found a second use. AOD-9604 was later accorded “generally recognised as safe” (GRAS) status in the US for use in foods, drinks and supplements, conditional on publication of the existing safety data; Moré and Kenley’s 2014 paper summarises the genotoxicity and six-month rat and nine-month primate toxicology behind it [6]. GRAS is a food-law status for oral ingestion. It is not a marketing authorisation, says nothing about efficacy, and has no bearing on injectable products.
In the US, AOD-9604 has also featured in FDA reviews of bulk substances nominated for pharmacy compounding, where the agency raised immunogenicity risk and “limited safety-related information” for the injectable route [7]. In the UK it has no licence of any kind; injectable AOD-9604 is sold under research-use labelling only.
AOD 9604 dosage: what the literature reports
The doses below are those used in the cited studies. They are not recommendations, and the rodent figures do not translate to humans.
| Study | Population | Dose used | Route and duration | Result |
|---|---|---|---|---|
| Ng et al. 2000 [1] | Zucker fatty rats | AOD9401 (177-191) | Injection, chronic | Reduced weight gain, no glucose change |
| Heffernan et al. 2001 [2] | ob/ob mice | Continuous infusion | Osmotic pump, 14 days | Less weight gain, more fat oxidation |
| METAOD001–004 [4] | Healthy adults | 25–400 mcg/kg IV; up to 54 mg oral | Single dose to 7 days | Safety only |
| METAOD005 [4] | Obese adults | Oral (within 0.25–54 mg/day range) | 12 weeks | Safety only reported |
| METAOD006 [4][5] | 536 obese adults | 0.25, 0.5, 1 mg/day oral | 24 weeks | No significant weight loss vs placebo |
Two things stand out. The doses actually tested in humans were oral and, in the pivotal trial, small. And the daily injectable doses circulating online have no clinical trial behind them; they are vendor convention, and no figure from that source is reproduced here.
Reconstituting a 5 mg vial
AOD-9604 and HGH Fragment 176-191 are supplied as lyophilised powder, most often in 5 mg vials. The concentration after reconstitution depends only on how much diluent is added:
Concentration (mg/mL) = 5 mg ÷ diluent volume (mL). Multiply by 1,000 for mcg/mL, and divide by 100 for mcg per unit on a U-100 insulin syringe.
Worked example: 5 mg + 2 mL bacteriostatic water = 2.5 mg/mL = 2,500 mcg/mL. Each unit on a U-100 syringe is 0.01 mL, so one unit holds 25 mcg and 10 units hold 250 mcg.
| Diluent added to 5 mg | Concentration | mcg per U-100 unit | Units for 250 mcg | Units for 500 mcg |
|---|---|---|---|---|
| 1 mL | 5 mg/mL (5,000 mcg/mL) | 50 | 5 | 10 |
| 2 mL | 2.5 mg/mL (2,500 mcg/mL) | 25 | 10 | 20 |
| 2.5 mL | 2 mg/mL (2,000 mcg/mL) | 20 | 12.5 | 25 |
| 3 mL | 1.67 mg/mL (1,667 mcg/mL) | 16.7 | 15 | 30 |
Once reconstituted, a vial drawn from repeatedly must be kept refrigerated and used within the 28-day window the preservative supports; see bacteriostatic water storage and shelf life.
Diluent choice
Multi-dose vials need a preserved diluent. Bacteriostatic water contains 0.9 per cent benzyl alcohol, which keeps the vial suitable for repeated draws for up to 28 days after first puncture; sterile water for injection has no preservative and is intended for a single draw. The comparison is set out in bacteriostatic water vs sterile water. Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials; the reconstitution guide covers the full method.
AOD-9604 is the best-studied compound in the metabolic peptides group and the clearest cautionary tale: clean mouse data, clean human safety, no human efficacy. The mitochondrial peptides MOTS-c and SS-31 have the opposite profile.
Frequently asked questions
Is HGH Fragment 176-191 the same as AOD-9604?
Yes. AOD-9604 is hGH residues 177–191 with an added N-terminal tyrosine, which gives the 176-191 numbering. Both names describe one 16-amino-acid peptide. Product differences are about supplier purity and vial fill, not the molecule, so any claim that one “works better” than the other has no pharmacological basis.
Does AOD-9604 raise blood sugar like growth hormone?
The evidence says no. In obese mice it increased fat oxidation without raising glucose or insulin, and in six human trials it had no effect on IGF-1 or carbohydrate metabolism. That is a real difference from GH. It is a statement about what the fragment does not do, not evidence that it produces fat loss.
What dose of AOD-9604 was used in human trials?
The phase 2b trial used oral tablets at 0.25, 0.5 or 1 mg daily for 24 weeks; earlier studies used intravenous doses of 25–400 mcg/kg and oral doses up to 54 mg/day. No injectable subcutaneous dose was tested in a published human trial, so online figures for injection have no trial basis.
Is AOD-9604 approved anywhere?
Not as a medicine. It failed to show weight loss in phase 2b and development stopped in 2007. It later gained US GRAS status as a food ingredient, which concerns oral safety at declared levels only. In the UK it is unlicensed and sold for research use.
References
- Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. Ng et al., Journal of Molecular Endocrinology, 2000
- Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan et al., International Journal of Obesity, 2001
- The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knock-out mice. Heffernan et al., Endocrinology, 2001
- Safety and tolerability of the hexadecapeptide AOD9604 in humans. Stier, Vos and Kenley, Journal of Endocrinology and Metabolism, 2013
- Metabolic Pharmaceuticals’ obesity trial update: first 100 subjects complete the phase 2B trial of AOD9604. BioSpace press release, 2006
- Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health. Moré and Kenley, Journal of Endocrinology and Metabolism, 2014
- Certain bulk drug substances for use in compounding that may present significant safety risks. US Food and Drug Administration, 2025
Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.