Peptide

AOD-9604

Tyr-hGH 177-191 (human growth hormone C-terminal fragment)

Evidence TierCWADA PROHIBITED

tuneTypical Dose

1 mg (reported 12-week signal context). 0.25-1 mg/day in long-duration oral phase IIb context.

watchEffect Window

Most reported effects are short-to-moderate duration. Durability remains unproven in later efficacy contexts.

lockCompliance

WADA PROHIBITED

Overview

Clinical Summary

AOD-9604 is a peptide fragment of human growth hormone developed to influence fat metabolism. It is used for body fat reduction goals with claims of minimal growth hormone effects.

Human trial outcomes for weight loss have been small or inconsistent despite plausible lipolysis mechanisms. Some preclinical work suggests effects on cartilage and tissue repair signaling. Minority claims include improved metabolic flexibility and reduced inflammation markers, but direct clinical confirmation is limited. Overall evidence does not strongly support meaningful fat loss effects.

Synthetic hGH C-terminal fragment intended to favor lipolysis with reduced IGF-1 pathway activation compared with full-length GH.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Weight change
  • Fat metabolism signals
  • IGF-1 and glucose neutrality

Secondary Outcomes

  • Tolerability
  • Adverse event profile
  • Protocol adherence

Safety

Contraindications and Interactions

Contraindications

  • Pregnancy
  • Breastfeeding
  • Children
  • Severe endocrine instability
  • Active malignancy
  • Unstable severe cardiac/renal/hepatic disease

Side effects

  • Injection site irritation
  • Headache
  • Chest tightness

Interactions

  • Other GH-axis peptides
  • Poly-stimulant stacks
  • Unknown endocrine modulators

Avoid if

  • Athlete context without compliance review
  • No physician oversight
  • Unregulated sourcing
  • Uncertainty-intolerant users

Evidence

Study-level References

aod-9604-SRC-001Human safety review of six trials

Stier M, et al. "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans." J Endocrinol Metab. 2013. doi:10.4021/jem157w.

Population: Healthy and obese adults across early AOD9604 clinical studies.

Dose protocol: IV 25-400 µg/kg and oral 0.25-54 mg/day across six early trials

Key findings: Public human data support short-term tolerability and relative endocrine neutrality more clearly than durable efficacy.

Notes: Best available human safety anchor for the compound.

Paper content

The public human safety review reported no treatment-related withdrawal or serious adverse-event pattern clearly attributable to AOD9604 and did not show an obvious IGF-1 or glucose-intolerance signal in aggregate.

aod-9604-SRC-002Animal study
Sourceopen_in_new

Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone Research. 2000;53(6). doi:10.1159/000053183. PMID:11146367.

Population: Obese Zucker rats

Dose protocol: 500 µg/kg/day oral for 19 days in obese Zucker rats

Key findings: Preclinical work showed reduced weight gain and increased lipolytic activity without a clear insulin-sensitivity penalty.

Notes: Animal-only evidence and not directly translatable to human efficacy.

Paper content

Oral AOD9604 at 500 microg/kg daily for 19 days reduced body weight gain by over 50% in obese Zucker rats and increased adipose tissue lipolytic activity. Unlike chronic treatment with intact hGH, AOD9604 did not impair insulin sensitivity, suggesting it may have potential as an orally usable therapeutic agent for obesity without the metabolic side effects of full-length growth hormone.

aod-9604-SRC-003Animal study
Sourceopen_in_new

Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity. 2001;25(10). doi:10.1038/sj.ijo.0801740. PMID:11673763.

Population: Obese (ob/ob) and lean C57BL/6J mice

Dose protocol: Chronic dosing in obese and lean mice

Key findings: AOD-9604 increased fat oxidation and reduced body-weight gain in obese mice without the broader GH-like metabolic liabilities.

Notes: Supports mechanism and preclinical plausibility only.

Paper content

Both hGH and AOD9604 reduced body weight gain, increased fat oxidation, and stimulated lipolysis in obese mice over 14 days. Critically, AOD9604 did not interact with the hGH receptor, did not induce cell proliferation, and did not cause hyperglycaemia or insulin resistance, unlike full-length hGH. This supports the concept that fragments of hGH can replicate its lipolytic actions without the associated metabolic side effects.

aod-9604-SRC-004Review
Sourceopen_in_new

Bray GA, Greenway FL. Pharmacological treatment of the overweight patient. Pharmacol Rev. 2007;59(2):151-84. doi:10.1124/pr.59.2.2. PMID:17540905.

Population: Review covering overweight and obese patients across clinical trials of pharmacological treatments

Dose protocol: Daily oral dosing for 12 weeks across 1-30 mg arms in obese adults

Key findings: In a 12-week randomized trial, subjects receiving AOD-9604 at 1 mg/day lost 2.6 kg on average compared to 0.8 kg in the placebo group. Weight loss was not dose-dependent, with 10 mg/day showing a smaller reduction.

Notes: Trial results documented in review literature. No standalone peer-reviewed publication of the primary trial data exists.

Paper content

This comprehensive review covers pharmacological approaches to treating overweight patients, including anti-obesity agents, anticonvulsants, second-generation antidepressants, appetite depressants, and complementary therapies. The review examines clinical trial data across multiple drug classes and discusses age and sex factors influencing treatment outcomes.

aod-9604-SRC-005Review
Sourceopen_in_new

Misra M. Obesity pharmacotherapy: current perspectives and future directions. Curr Cardiol Rev. 2013;9(1):33-54. doi:10.2174/157340313805076322. PMID:23092275.

Population: Obese individuals and those with obesity-related metabolic disorders

Dose protocol: Later multi-arm 24-week obesity development context

Key findings: A 24-week trial of 536 obese subjects failed to demonstrate significant weight loss. Development was terminated in 2007.

Notes: The trial failure is documented in review literature. Important for preventing overstatement of the earlier 12-week signal.

Paper content

This review examines the current landscape of obesity pharmacotherapy, noting that existing medicines remain limited in number and effectiveness. The author discusses recent advances in understanding the neuroendocrine regulation of body weight and energy metabolism, highlighting emerging therapeutic targets and future directions for anti-obesity drug development.

aod-9604-SRC-006Validation study
Sourceopen_in_new

Cox HD, Smeal SJ, Hughes CM, et al. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015;7(1):31-38. doi:10.1002/dta.1715. PMID:25208511.

Population: In vitro samples for anti-doping detection method development

Dose protocol: Analytical detection workflow in anti-doping context

Key findings: AOD-9604 has a published anti-doping detection method and carries clear sport-governance risk.

Notes: Governance and detectability source, not efficacy evidence.

Paper content

This study describes the detection and in vitro metabolism of AOD9604, a peptide derived from the C-terminal fragment of human growth hormone (amino acids 177-191) with an additional tyrosine residue. AOD9604 is reported to mimic the lipolytic properties of growth hormone without diabetogenic side effects. The authors developed and validated an LC-MS/MS method for detecting AOD9604 and its metabolites in blood and urine for anti-doping purposes.

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