Compound reference

AOD-9604

Also known as Lipotropin, Tyr-hGH 177-191

A synthetic fat-loss fragment of human growth hormone. It was well tolerated in humans, but its pivotal obesity trial failed and pharmaceutical development was discontinued in 2007; it is unapproved and prohibited in sport.

· 3 min read

CAS
221231-10-3
Molar mass
≈1,817 g/mol
Sequence
Tyr-hGH(177–191) — 16-residue C-terminal fragment of human growth hormone

Research peptide; not FDA-approved as a drug, and evidence claims should be handled conservatively.

Mode of action

AOD-9604 is a synthetic 16-residue peptide based on the C-terminal lipolytic domain of human growth hormone (hGH 177–191), with an added N-terminal tyrosine. The design goal was to isolate growth hormone's fat-metabolising activity — stimulating lipolysis and inhibiting lipogenesis in adipose tissue — while leaving out the parts of the hormone that raise IGF-1, drive tissue growth, or impair glucose handling. In rodent obesity models it reduced body-fat gain without the glycemic penalty seen with full-length hGH. The mechanism is preclinical and proposed; how it acts at the molecular level in humans is not firmly established.

Main intended effect

AOD-9604 was developed as an anti-obesity drug — the "AOD" stands for anti-obesity drug — aiming for fat loss through increased lipolysis while sparing appetite, muscle, and glucose metabolism.

Areas of interest

Originally a pharmaceutical obesity candidate (developed from work at Monash University in Australia), it later resurfaced in aesthetic and "research-chemical" channels as a fat-loss compound, and it carries a doping-control history. Most current interest is gray-market fat loss rather than any active clinical program.

Evidence for intended effects

This is, in essence, a clinical failure story. Preclinical work in obese Zucker rats and ob/ob mice showed reduced fat and body-weight gain without the glycemic harm of growth hormone, and an early Phase IIa signal appeared (10 mg/day for a week produced ~1.0 kg loss versus 0.4 kg on placebo). But across six randomized, double-blind, placebo-controlled human trials between 2001 and 2007 in roughly 893 obese adults, the pivotal 24-week Phase IIb did not show statistically significant, dose-dependent weight loss, and pharmaceutical development was discontinued in 2007. Tellingly, safety was consistently good — the failure was efficacy, not tolerability.

Strand What exists Tier
Fat loss (animal) Obese Zucker rat / ob-ob mouse models Preclinical (positive)
Fat loss (human) Six RCTs incl. a 24-week Phase IIb Phase 2 — efficacy not shown
Safety / tolerability Six human trials, ~893 adults Good (placebo-like)

Studied amounts (literature dosing context)

Human trials tested oral doses from about 0.25 to 30 mg/day and intravenous doses of roughly 25–400 µg/kg. These are amounts from a development program that did not establish efficacy; there is no approved dose, and this page does not provide dosing guidance.

Safety and regulatory status

AOD-9604's human safety profile was favourable — comparable to placebo, and without the IGF-1 elevation, insulin resistance, or impaired glucose tolerance that limit full growth hormone. That clean tolerability is the main thing the trials established.

On regulation, AOD-9604 is not an approved drug; its obesity program ended after the failed pivotal trial. The FDA has flagged it (barred from compounding), it is prohibited in sport by the World Anti-Doping Agency, and it circulates online as an unregulated "research chemical" of unverified content.

Sources

  1. Safety and tolerability of the hexadecapeptide AOD9604 in humans safety · Journal of Endocrinology and Metabolism ·

    Review of human safety data for AOD9604 (Stier, Vos, Kenley, Journal of Endocrinology and Metabolism, 2013), summarizing six clinical trials conducted between 2001 and 2006 in 893 healthy and clinically obese adults. It details the single and multiple oral doses tested (e.g. 9, 27, 54 mg capsules; 0.25, 0.5, 1 mg tablets) and intravenous doses (25, 50, 100 µg/kg). AOD9604 showed a safety and tolerability profile indistinguishable from placebo, without the IGF-1 elevation, insulin resistance, or impaired glucose tolerance seen with full-length human growth hormone.

    https://www.jofem.org

  2. Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health safety · Journal of Endocrinology and Metabolism ·

    Safety and metabolism review (Moré and Kenley, Journal of Endocrinology and Metabolism, 2014) of AOD9604, the C-terminal fragment (Tyr-hGH177-191) of human growth hormone, framing it as a candidate nutraceutical ingredient after its pharmaceutical obesity program. It summarizes six completed human clinical trials — including two intravenous and two oral pilot studies and two oral Phase IIb studies enrolling up to 500 obese adults — and concludes AOD9604 was generally safe and well tolerated, with intended effects of stimulating lipolysis and inhibiting lipogenesis.

    https://www.jofem.org

  3. 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 preclinical · Endocrinology ·

    Heffernan and colleagues tested AOD9604, a lipolytic fragment derived from the C-terminus of human growth hormone, against full-length hGH over 14 days of chronic intraperitoneal dosing in obese mice and beta(3)-adrenergic-receptor (beta3-AR) knockout mice with wild-type controls, measuring body weight, body fat, beta3-AR RNA expression, lipolysis, energy expenditure, and fat oxidation. Both hGH and AOD9604 reduced body weight and body fat and increased lipolytic sensitivity in obese mice, restoring the repressed beta3-AR RNA toward lean-mouse levels. In beta3-AR knockouts, chronic treatment failed to change body weight or increase lipolysis, yet acute AOD9604 still enhanced energy expenditure and fat oxidation, leading the authors to conclude the lipolytic effect is not mediated directly through the beta3-AR. These are rodent data; human efficacy and safety of AOD-9604 are unestablished.

    https://pubmed.ncbi.nlm.nih.gov/11713213/

  4. Novel targets for the treatment of obesity: a review of progress review · Drug Discovery Today: Therapeutic Strategies ·

    Review of emerging anti-obesity drug targets (Cheetham and colleagues, Drug Discovery Today: Therapeutic Strategies, 2004) describing AOD-9604 as an orally active fragment of human growth hormone (hGH 177–191) that selectively activates lipolysis in adipose tissue. It reports a Phase IIa study in which obese volunteers taking 10 mg/day for seven days lost 1.0 kg versus 0.4 kg on placebo (with a Phase IIb then underway), and notes preclinical weight reduction in obese Zucker rats and ob/ob mice without the adverse glycemic effects of growth hormone.

    https://www.sciencedirect.com/journal/drug-discovery-today-therapeutic-strategies

  5. Obesity Pharmacotherapy: Current Perspectives and Future Directions review · Current Cardiology Reviews ·

    Misra's review of obesity pharmacotherapy in Current Cardiology Reviews surveys approved and investigational anti-obesity agents and documents AOD-9604, an orally active analogue of the human growth hormone 177-191 fragment that selectively activates adipose-tissue lipolysis. Preclinical testing in genetically obese Zucker rats and ob/ob mice reduced body weight without the adverse glycemic effects associated with growth hormone, and a 12-week randomized clinical study of 1 mg daily produced an average 2.6 kg weight loss versus 0.8 kg with placebo. Critically, the review records that AOD-9604 development ceased in 2007 after the compound failed to induce significant weight loss in a 24-week trial of 536 subjects. This secondary review summarizes the human evidence and the discontinuation; AOD-9604 is not an approved therapeutic, and its weight-loss efficacy was not confirmed in the pivotal trial.

    https://pmc.ncbi.nlm.nih.gov/articles/PMC3584306/

  6. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance review · Sports Medicine ·

    Narrative review (Mendias and Awan, Sports Medicine, 2026) of approved and unapproved peptides marketed for musculoskeletal healing and athletic performance — including AOD-9604, CJC-1295, BPC-157, and others. For AOD-9604 it summarizes six randomized double-blind placebo-controlled human trials in over 900 patients that showed a favorable short-term safety profile but failed to demonstrate statistically significant dose-dependent weight loss versus placebo. The review's broader message is that many unapproved peptides carry potential for serious harm despite favorable tissue-repair or metabolic signals in animal models.

    https://link.springer.com/journal/40279

  7. Detection and in vitro metabolism of AOD9604 safety · Drug Testing and Analysis ·

    Analytical study (Cox and colleagues, Drug Testing and Analysis, 2015) developing methods to detect AOD9604 — a human growth hormone fragment (amino acids 176–191 with an added tyrosine) intended to mimic the lipolytic properties of growth hormone without diabetogenic effects. The authors identified six potential metabolites in serum and urine, note that AOD9604 is available online and has appeared in confiscated vials, and that it is prohibited by the World Anti-Doping Agency as a potential performance-enhancing drug.

    https://onlinelibrary.wiley.com/journal/19427611