An evidence page summarising and grading the published record. It does not recommend use. Where trial doses appear, they describe the studies that were run, not a protocol to follow.

01 Identity

Common name	AOD-9604
Meaning	"Anti-Obesity Drug 9604"
Class	Synthetic 16-amino-acid peptide; C-terminal fragment of human growth hormone (residues 177–191) with an added N-terminal tyrosine
Origin	Metabolic Pharmaceuticals (Australia), 1990s–2000s
Route studied	Oral (tablet) in the pivotal human trials
CAS number	221231-10-3 · PubChem CID 71300630 · confirmed

Designed to isolate the lipolytic ("fat-burning") portion of growth hormone's C-terminal domain while avoiding its anabolic and glucose-disrupting effects. A repeatedly reported feature is that it does not raise IGF-1 or disturb glucose homeostasis — part of why its eventual efficacy failure is informative rather than trivial.

02 Regulatory status

AOD-9604 holds no marketing authorisation anywhere and is not approved by the FDA, EMA, or MHRA for any indication. Its pharmaceutical development for obesity was terminated in 2007 after the pivotal trial (see §5).

In December 2024 the FDA determined that AOD-9604 should not be added to the 503A bulk-substances list for pharmacy compounding, citing limited long-term safety data, peptide impurities, and potential immunogenicity. The World Anti-Doping Agency lists it as a prohibited substance (class S2). Regulatory specifics change; confirm against FDA and WADA primary documents.

03 Mechanism of action

The proposed mechanism is stimulation of lipolysis and inhibition of lipogenesis, mimicking the lipolytic action attributed to growth hormone's C-terminal region, with reported β3-adrenergic involvement in animals. The design intent — lipolysis without IGF-1 elevation or glucose disruption — appears to have been achieved pharmacologically.

The mechanism is reasonably characterised in animals. The problem AOD-9604 illustrates is downstream: a coherent mechanism and positive rodent data did not translate into a clinically meaningful human effect.

04 Pharmacokinetics / pharmacodynamics

Formulated for oral administration in the pivotal trials (once-daily tablet), with human exposure characterised sufficiently to run dose-ranging efficacy trials (0.25, 0.5, and 1 mg daily vs placebo).

Detailed human PK parameters are not well represented in the peer-reviewed literature; specifics should be drawn from the trial records rather than estimated.

05 Evidence by endpoint

5.1 — Weight / fat loss in obesity — the central question

The evidence has a characteristic shape: a positive early signal that did not survive a larger, longer trial. An early Phase 2a (≈12 weeks, ~300 participants) reported modest weight reduction (≈2.6 kg vs 0.8 kg placebo). The pivotal Phase 2b (24 weeks, n≈534; oral; dose-ranging vs placebo; 2007) did not meet its primary weight-loss endpoint at any dose, and development was discontinued. The detailed Phase 2b results were not published in a peer-reviewed journal, which is its own kind of result. Later reviews conclude AOD-9604 does not produce clinically meaningful fat loss.

Contested / negative

5.2 — Osteoarthritis / cartilage repair

Explored after the obesity programme ended; early-stage and preclinical, without the human efficacy base of the obesity work.

Preclinical only

5.3 — Lipolytic mechanism in animals

Rodent studies reported increased fat metabolism and reduced weight gain. The mechanism was supportive; it was never reproduced as a clinical effect in humans (see §5.1).

Preclinical

06 Safety and adverse events

AOD-9604 is unusual among the unapproved peptides here in that it does have a substantial human safety dataset — around six randomised, double-blind, placebo-controlled trials involving over 900 participants. Across that programme it was generally well tolerated, with no IGF-1 elevation, no reported glucose disruption, and no notable adverse signal at the doses and durations tested.

Two cautions qualify that. Long-term human safety is still not established (trials ran weeks to months). And the FDA's 2024 compounding determination cited peptide impurities and potential immunogenicity — issues attaching to the manufactured product's quality, not only the molecule. The honest summary is the inverse of a compound like KPV: here the human safety data exists and is broadly reassuring short-term, while it is the efficacy the evidence weighs against.

07 Evidence summary

Endpoint	Grade
Weight / fat loss (obesity)	Contested / negative
Osteoarthritis / cartilage	Preclinical only
Lipolytic mechanism (animal)	Preclinical
Short-term human safety	Characterised · broadly tolerated
Long-term human safety	No data

08 References

Ng FM, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. (Rodent mechanism.)Confirm full citation and year before publication
Metabolic Pharmaceuticals — Phase 2b obesity trial (≈534 participants, 24 weeks, oral, dose-ranging vs placebo), reported 2007.Pivotal results announced as not meeting the primary endpoint; not subsequently published in full — state explicitly
Contemporaneous trial reporting, 2006–2007 (industry disclosure of Phase 2b design and outcome).Add trial-registry entry if one exists
FDA — 503A bulk drug substances determination on AOD-9604, December 2024.Cite the FDA document directly
World Anti-Doping Agency — Prohibited List (class S2).Confirm current listing