metabolichGH fragment 176-191

AOD-9604

AOD-9604 is a 16 amino acid peptide corresponding to residues 177-191 of the human growth hormone C-terminus with a tyrosine added at the N-terminus. It was developed at Monash University in Australia by Frank Ng and colleagues and taken forward by Metabolic Pharmaceuticals as an anti-obesity candidate. The premise came from earlier work showing that the fat-metabolizing activity of growth hormone sits in a discrete region of the molecule that can be separated from the growth-promoting activity, which is what the fragment was designed to isolate.

class
modified C-terminal fragment of human growth hormone (Tyr-hGH 177-191)
route
subcutaneous in self-directed use; the human trials used oral dosing
plasma half-life
short, reported on the order of tens of minutes after parenteral dosing
typical dose
300 mcg once daily fasted, 250 to 600 mcg total daily range
IGF-1 effect
none reported at studied doses, unlike GH or GH secretagogues
storage
lyophilized refrigerated or frozen; reconstituted 2–8°C, 28-day max
Dose calculatorlive
U-100
Concentration
2.50mg/mL
Injection vol.
0.120mL
Syringe cap.
100units
Draw to12units
02040608010012 units
Dosing guide

AOD-9604 Reconstitution & Dosage Protocol

weekly dose · reduces side effects
PhaseWindowWeekly doseDraw (U-100, 2mL BAC)Note
Tolerance startDays 1–30.15 mg6 units· 0.06 mL150 mcg once in the morning. At 2.5 mg/mL (5 mg vial in 2 mL BAC water) this is 0.06 mL, which is 6 units on a U-100 syringe. AOD-9604 is one of the better tolerated research peptides, so this step is mostly about confirming the vial reconstituted cleanly and that the injection site behaves, not about managing systemic effects
Standard dailyWeeks 1–120.30 mg12 units· 0.12 mL300 mcg once daily on an empty stomach, typically on waking with food delayed 30 to 60 minutes. At 2.5 mg/mL this is 0.12 mL, which is 12 units. The fasted requirement matters here for the same reason it does with GH secretagogues: insulin is antilipolytic, and eating before the dose works directly against the mechanism you are dosing for
Split dosingOptional0.30 mg12 units· 0.12 mLA second 300 mcg dose in the evening, at least 2 hours after the last meal, brings the daily total to 600 mcg. The short plasma half-life is the usual rationale for splitting. There is no human dose-response data supporting 600 mcg over 300 mcg, so treat this as preference rather than an established improvement
Upper single doseAs used0.50 mg20 units· 0.20 mL500 mcg as a single fasted dose, which is 0.2 mL or 20 units at 2.5 mg/mL. This is the top of what appears in self-directed protocols. The published human work never established a subcutaneous dose-response curve, so higher figures circulating online are extrapolation, not evidence
ReassessWeek 120.00 mg0 units· 0.00 mLStop and evaluate against objective measures (weight, waist circumference, body composition) rather than perceived effect. The largest human trial ran 24 weeks and did not separate from placebo on its primary endpoint, so an honest 12-week checkpoint is the point at which continuing should require actual evidence it is doing something
How it works

What is AOD-9604?

AOD-9604 is a 16 amino acid peptide corresponding to residues 177-191 of the human growth hormone C-terminus with a tyrosine added at the N-terminus. It was developed at Monash University in Australia by Frank Ng and colleagues and taken forward by Metabolic Pharmaceuticals as an anti-obesity candidate. The premise came from earlier work showing that the fat-metabolizing activity of growth hormone sits in a discrete region of the molecule that can be separated from the growth-promoting activity, which is what the fragment was designed to isolate.

That separation is the entire point of the compound. Full growth hormone raises IGF-1, can worsen insulin sensitivity, and drives tissue growth. AOD-9604 does not bind the growth hormone receptor and, in the animal and human work published, did not raise IGF-1 or disturb blood glucose at the doses studied. What it did do in obese mice was increase lipolysis, reduce lipogenesis, and lower body weight gain and adipose mass. The 2001 Endocrinology work by Heffernan and colleagues also tested it in beta3-adrenergic receptor knockout mice, which mattered because an early hypothesis held that the fragment worked by upregulating beta3-AR; the knockout results argued the effect was not dependent on that receptor.

The human program is where expectations should be set carefully. The clinical trials that generated the compound's reputation used ORAL dosing in obese subjects, not injection. A 12-week phase 2b program reported modest weight loss favoring the drug over placebo, and on that basis the compound advanced. A subsequent longer trial running roughly 24 weeks failed to separate from placebo on its primary weight endpoint, and commercial development as an obesity drug effectively stopped there. AOD-9604 has never been approved as a drug in any jurisdiction.

Its afterlife has been in two other places. In the United States it went through a self-affirmed GRAS determination in 2014 aimed at use as a food ingredient, and it has since been sold in the grey market for research purposes only. The FDA has separately flagged it in its evaluation of substances nominated for use in compounded drug products, placing it in the category of substances raising significant safety concerns rather than the approved-for-compounding list. Anti-doping science has paid it real attention: it is prohibited by WADA as a growth hormone fragment, and Drug Testing and Analysis has published both an in vitro metabolism and detection method for it and a 2013 paper confirming it does not interfere with the WADA hGH isoform immunoassay, meaning it requires its own detection approach.

A separate research thread looks at AOD-9604 in cartilage rather than fat. A 2015 rabbit osteoarthritis model published in Annals of Clinical and Laboratory Science tested intra-articular injection with and without hyaluronic acid and reported improvement in cartilage measures. This is the origin of the joint and tendon claims attached to the peptide in self-directed use. It is a single small animal study using a route (into the joint) that has nothing in common with the subcutaneous abdominal injection people actually perform, and it should not be read as support for that practice.

Common questions

AOD-9604 Frequently Asked Questions

Self-directed protocols run 250 to 300 mcg once daily subcutaneously in a fasted state, with a total daily range of roughly 250 to 600 mcg when split into two doses. These numbers come from community practice, not from a label or a dose-finding trial. The published human trials used oral administration, so there is no controlled human data establishing an optimal subcutaneous dose.
Sources

Research & References

Effect of an antilipogenic fragment of human growth hormone on glucose transport in rat adipocytesPubMed · Biochemistry and Molecular Biology International 1993Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptidePubMed · Biochemistry and Molecular Biology International 1994Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormonePubMed · Hormone Research 2000Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragmentPubMed · International Journal of Obesity 2001The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta3-AR knock-out micePubMed · Endocrinology 2001AOD-9604 does not influence the WADA hGH isoform immunoassayPubMed · Drug Testing and Analysis 2013Detection and in vitro metabolism of AOD9604PubMed · Drug Testing and Analysis 2015Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis modelPubMed · Annals of Clinical and Laboratory Science 2015
Also calculate

Related Peptide Calculators