JACKEDFORUMS

AOD-9604

Anti-Obesity Drug 9604 · AOD9604 · Tyr-hGH(177-191) · Modified GH fragment 176-191

Modified hGH tail fragment sold for lipolysis without the IGF-1 rise of growth hormone.

Typical dose

300 mcg

once daily

Range

250–500

mcg

Half-life

3 min

see Dosing

Evidence

Human trials

Subcutaneous · Oral

What it is

AOD-9604 is a 16-amino-acid fragment of the C-terminus of human growth hormone with a tyrosine on the front end. It came out of Monash University and was developed by Metabolic Pharmaceuticals on the premise that GH's fat-burning activity lives in this end of the molecule, separate from the growth and insulin-antagonising effects.

In rodents the premise held up: obese mice treated with AOD-9604 increased fat oxidation and lost weight without the IGF-1 elevation or insulin resistance that full-length GH causes. Human results did not follow. A 12-week phase 2a trial at 1 mg orally showed about 2.6 kg lost versus 0.8 kg on placebo, but the larger 24-week phase 2b in 536 subjects missed on weight loss and development was terminated in 2007.

So the honest position is this: AOD-9604 is one of the most-studied peptides on the fat-loss shelf and it is also one of the few with a clearly negative human trial behind it. It is extremely well tolerated — no IGF-1 movement, no glucose effect, essentially no side-effect signal — which is a different thing from being effective.

A secondary line of research looked at intra-articular use for cartilage and osteoarthritis. That work is animal-stage and does not support the joint-repair claims made by vendors.

How it works

The C-terminal region of growth hormone appears to stimulate lipolysis and inhibit lipogenesis in adipocytes, and in rodent work it does so partly through beta-3 adrenergic receptor expression rather than the GH receptor itself. Because the fragment does not bind the GH receptor in the way the intact hormone does, it does not raise IGF-1, does not blunt insulin sensitivity, and does not carry GH's growth signalling.

That receptor independence is also the problem: the beta-3 adrenergic pathway that carries the effect is far more prominent in rodent adipose tissue than in human adipose tissue, which is the most likely explanation for why the mouse data never translated to a human trial endpoint.

Dosing

Typical single dose300 mcg
Reported range250–500 mcg
Frequencyonce daily
Injections per week7
Half-lifeMinutes — around 3-4 minutes in plasma after IV dosing in animals; subcutaneous kinetics in humans have not been published
TimingFasted — first thing in the morning or pre-bed, at least 2 hours clear of food, on the theory that insulin blunts lipolysis.
Typical run length8-12 weeks
RoutesSubcutaneous, Oral
Molecular weight1815 Da
SequenceYLRIVQCRSVEGSCGF

The community 250-500 mcg subcutaneous range has no trial behind it; the human trials used 1 mg orally once daily and the larger one failed its endpoint.

Reconstitution calculator

Pre-loaded with AOD-9604’s vial size, water volume and typical dose. Change anything.

Typical: 300 mcg · range 250–500

05101520253030 units0.3 mL insulin · U-100 · half-unit marks

Draw to

30 u

0.3 mL · 300 mcg

Concentration

1 mg/mL

10 mcg per unit

Doses per vial

6.7

Vial lasts

7 days

CheckThe draw fills more than 90% of the barrel. Workable, but there is no room for an air bubble or a correction.

Once mixed
2-8 C, use within 3-4 weeks with bacteriostatic water. Do not freeze and thaw repeatedly.

Full calculator →
Suggested water2 mL per 2 mg vial
Common vial sizes2 mg, 5 mg

2 mL of bacteriostatic water into a 2 mg vial gives 1 mg/mL, so 300 mcg is 30 units on a U-100 insulin syringe. Run the water down the side of the vial and swirl — this fragment carries a disulfide bridge and shaking degrades it.

Storage

Before mixing

2-8 C and dark; stable for a year or more, and tolerates a few weeks at room temperature during shipping.

After mixing

2-8 C, use within 3-4 weeks with bacteriostatic water. Do not freeze and thaw repeatedly.

Reported benefits

  • Increased fat oxidation and reduced lipogenesis in rodent adipose tissue
  • No measurable IGF-1 elevation, unlike GH or GH secretagogues
  • No effect on blood glucose or insulin sensitivity in human trials
  • Very clean tolerability profile across multiple human studies
  • Does not suppress the HPTA or the GH axis, so it can sit alongside anything
  • Preliminary animal work on intra-articular use in osteoarthritis

Side effects

  • Injection site redness or itching, usually transient
  • Occasional headache or light-headedness
  • Rare mild GI upset with the oral form
  • Hypersensitivity reactions in principle, as with any injected peptide
  • No signal for IGF-1 rise, water retention, carpal tunnel or glucose disturbance in human trials
  • The main practical risk is spend without result — the largest human trial found no significant weight loss

Do not use if

  • Drug-tested athletes — AOD-9604 is a WADA prohibited substance and is detectable in urine
  • Active malignancy, on theoretical grounds shared with GH-related peptides
  • Pregnancy or breastfeeding
  • Known hypersensitivity to the peptide or to preservatives in bacteriostatic water

Evidence level — Human trials

Controlled human clinical data exists.

Not approved as a drug in any market and prohibited in sport under the WADA code; an oral form holds US self-affirmed GRAS status as a food ingredient, and injectable material is sold only as a research chemical.

Commonly run with

AOD-9604 FAQ

Is AOD-9604 different from HGH fragment 176-191?+

Chemically they are near-identical, but they are not the same molecule. Residue 176 of mature hGH is phenylalanine, so the native fragment 176-191 is FLRIVQCRSVEGSCGF. AOD-9604 is hGH 177-191 with a tyrosine put on the front instead of that phenylalanine, giving YLRIVQCRSVEGSCGF — one residue different, and 1815.1 Da against 1799.1 Da. The tyrosine was added so the peptide could be radioiodinated for tracer work. The practical difference is provenance and stability claims, not pharmacology, so expect the same results from both.

Why do people still run it if the phase 2b failed?+

Because it is cheap, does nothing to IGF-1 or glucose, and stacks with everything, so the downside is limited to cost. That is a reasonable position to hold as long as you are honest that the best human evidence is negative.

Does it need to be injected fasted?+

The fasted-dosing convention comes from GH practice — insulin opposes lipolysis, so people dose away from carbohydrate. It is a sensible heuristic rather than something demonstrated for this fragment specifically.

Will it show on a drug test?+

Yes. AOD-9604 is on the WADA prohibited list and validated urine detection methods for it have been published since 2014. Tested competitors should treat it as an out-of-competition positive risk.

References

  1. 1.Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormoneHormone Research (2000) PMID 11146367
  2. 2.Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragmentInternational Journal of Obesity and Related Metabolic Disorders (2001) PMID 11673763
  3. 3.Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis ModelAnnals of Clinical and Laboratory Science (2015) PMID 26275694
  4. 4.Detection and in vitro metabolism of AOD9604Drug Testing and Analysis (2015) PMID 25208511

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