Overview
HGH Fragment 176-191 is a synthetic peptide corresponding to amino acids 176 through 191 of the C-terminal region of human growth hormone (hGH). It is structurally identical or near-identical to AOD-9604, and the two are often discussed interchangeably. The fragment was developed at Monash University in Australia in the 1990s with the goal of isolating the lipolytic activity of GH while eliminating its growth-promoting and insulin-antagonistic effects.
Full-length growth hormone produces both desirable effects (lipolysis, lean-mass support) and undesirable effects (insulin resistance, IGF-1-mediated tissue growth, fluid retention). By using only the lipolytic C-terminus, researchers hoped to obtain a peptide that mobilized fat without raising IGF-1 or impairing glucose tolerance. In animal studies this strategy worked—rodents given HGH Fragment 176-191 lost adipose mass without changes in circulating GH or IGF-1.
Translating these findings to humans has been more difficult. The most extensive clinical program for AOD-9604 included multiple Phase IIb obesity trials sponsored by Metabolic Pharmaceuticals; while the peptide was well tolerated, the magnitude of weight loss did not reach statistical or clinical significance over placebo. AOD-9604 was subsequently repositioned as a food/cosmetic ingredient and later evaluated for osteoarthritis rather than obesity.
HGH Fragment 176-191 is not FDA-approved for any indication. It is widely sold as a research chemical and is sometimes included in compounded weight-loss formulations through non-FDA pathways. There are no large modern controlled human trials demonstrating clinically meaningful body-composition change from this peptide alone.
Quick facts
- Mechanism
- C-terminal GH fragment selectively stimulating lipolysis without GH/IGF-1 effects
- Primary use
- Selective fat-metabolism research
- Evidence
- limited
- FDA
- Not approved
- Route
- Subcutaneous injection, typically in a fasted state
- Typical results
- Modest reductions in adipose tissue over 8–12 weeks in animal models; human trials have not consistently reproduced clinical weight loss
Chemical information
HGH Fragment 176-191 (C₇₈H₁₂₅N₂₃O₂₃S₂) is a metabolic compound with a molecular weight of 1815 g/mol. Its structural characteristics underpin its biological activity in metabolic regulation and energy homeostasis.
How HGH Fragment 176-191 works
HGH Fragment 176-191 is thought to act on β3-adrenergic-receptor-coupled pathways in adipocytes, increasing intracellular cAMP, activating hormone-sensitive lipase, and promoting hydrolysis of stored triglycerides into free fatty acids and glycerol. Unlike full-length GH, the fragment does not bind the GH receptor with high affinity and therefore does not generate downstream JAK2/STAT5 signaling, IGF-1 induction, or insulin-receptor antagonism.
Preclinical studies in obese rodents have shown that HGH Fragment 176-191 increases lipolytic enzyme activity in white adipose tissue and inhibits lipogenesis in the same depots, producing a net reduction in fat mass over 4–8 weeks. The same studies report no change in IGF-1, glucose, or insulin, supporting the 'selective lipolysis' hypothesis at preclinical doses.
Mechanistic work suggests the fragment binds a distinct, GH-receptor-independent site on adipocytes. The β3-adrenergic axis appears central: β3 knockouts lose responsiveness to the fragment, and pharmacologic β3 antagonism abolishes its lipolytic effects in vitro.
Human pharmacokinetic data are sparse. Subcutaneous dosing produces plasma peaks within ~15–30 minutes and the peptide is cleared rapidly thereafter. Whether the brief plasma exposure achieves meaningful intracellular signaling at adipocyte targets in vivo remains a key uncertainty and is the most plausible explanation for the negative weight-loss outcomes in clinical trials.
- Selective lipolysis: Stimulates fat breakdown without GH-receptor activation
- β3-adrenergic axis: Effects depend on β3-receptor signaling in adipocytes
- No IGF-1 induction: Does not raise IGF-1 or impair glucose tolerance in animal models
- Short plasma exposure: Rapid clearance after subcutaneous dosing
- Weak clinical signal: Human obesity trials did not reach efficacy endpoints
Pharmacokinetics
| Parameter | Value | Significance |
|---|---|---|
| Molecular Mass | 1815 g/mol | Compact 16-residue peptide |
| Plasma half-life | ~15–30 minutes | Brief systemic exposure per dose |
| Bioavailability (SC) | Moderate | Subcutaneous is the typical research route |
| Bioavailability (oral) | Very low | Peptide is degraded in the GI tract |
| Metabolism | Enzymatic peptide hydrolysis | No CYP450 interactions expected |
Dosing & administration
HGH Fragment 176-191 dosing varies by indication and individual factors. No FDA-approved dosing exists for this compound; protocols in the literature derive from limited clinical or preclinical data and practitioner experience.
Any use should be conducted under qualified medical supervision with appropriate monitoring of safety markers.
Important: These dosing ranges are not FDA-approved. Any use should be under qualified medical supervision.
Side effects & safety
Safety data for HGH Fragment 176-191 is primarily derived from preclinical studies and limited human data. Long-term effects in humans remain incompletely characterized.
Common
- • Injection-site redness or itching
- • Mild headache
- • Transient fatigue or lightheadedness
- • Occasional GI upset
Serious / potential risks
- • Hypersensitivity reactions (rare)
- • Unknown long-term safety in humans
- • Cardiovascular effects from excessive free fatty acid release (theoretical)
- • Lack of efficacy in controlled trials raises concerns about misleading marketing
Drug interactions
| Medication | Interaction | Recommendation |
|---|---|---|
| β3-adrenergic agonists | Additive lipolytic signaling | Combination may amplify free fatty acid release and cardiovascular load |
| Beta blockers (non-selective) | Block lipolytic pathway | Expect attenuated effects of the fragment |
| Insulin and oral hypoglycemics | Generally neutral; no IGF-1 induction | Standard glucose monitoring |
| Other weight-loss agents (GLP-1 agonists, stimulants) | Unstudied combinations | Avoid stacking without medical supervision |
Storage & handling
Lyophilized (powder)
- • Store at -20°C to 4°C (freezer or refrigerator)
- • Protect from light and moisture
- • Stable for 12–24 months when stored properly
- • Keep in original sealed container until reconstitution
Reconstituted solution
- • Refrigerate at 2–8°C after reconstitution
- • Use bacteriostatic water for multi-dose reconstitution
- • Typical stability: 14–28 days refrigerated
- • Do not freeze reconstituted solution
Cost & availability
| Source | Cost | Notes |
|---|---|---|
| Research suppliers | Varies widely | Quality and purity vary significantly between sources |
| Compounding pharmacies | Prescription required | Higher quality assurance and purity testing |
The bottom line
HGH Fragment 176-191 is a metabolic compound with research interest in fat metabolism, weight loss, lipolysis. While preclinical evidence is encouraging, it remains investigational and is not FDA-approved. Any use should be under qualified medical supervision.
Best for
- • Researchers studying metabolic regulation and energy homeostasis
- • Individuals interested in fat metabolism under medical guidance
Not for
- • Self-administration without medical supervision
- • Pregnant or breastfeeding individuals
- • Individuals with contraindicated conditions
Related compounds
Frequently asked questions
References
- [1] Heffernan M, Summers RJ, Thorburn A, et al.. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knockout mice. Endocrinology (2001). doi: 10.1210/endo.142.12.8520 PMID: 11713218
- [2] Ng FM, Sun J, Sharma L, et al.. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res (2000). doi: 10.1159/000023253 PMID: 10810254
- [3] Stier H, Vos E, Kenley D.. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J Endocrinol Metab (2013).