For research and educational purposes only · Not medical advice · Consult a qualified physician before any human use
GH Fragment 176-191 is the unmodified 16-amino-acid C-terminal fragment of human growth hormone (residues 176-191), identified as responsible for growth hormone's lipolytic activity. It differs from AOD-9604 (profiled at order 33) by a single amino acid at the N-terminus: phenylalanine versus tyrosine. Critically, GH Fragment 176-191 has no published human clinical trial. Every human clinical finding in this peptide class belongs to AOD-9604 specifically. Animal evidence shows significant fat oxidation and weight loss in obese mice without GH receptor activation or IGF-1 elevation. WADA explicitly names both AOD-9604 and hGH 176-191 as prohibited growth hormone fragments under S2.
GH Fragment 176-191 (the unmodified fragment, beginning with phenylalanine) has no published human clinical trial. The six METAOD trials (METAOD001 through METAOD006) that are commonly cited for this compound class were all conducted with AOD-9604, the modified version in which N-terminal phenylalanine is replaced with tyrosine. Wikipedia states directly: 'In contrast to AOD9604, hGH frag 176-191 has not been studied in humans.' When vendors or biohacker sources cite 'clinical trials' for GH Fragment 176-191, they are citing AOD-9604 data. These are different compounds.
The AOD-9604 clinical program found a modest 12-week signal (2.6 kg vs 0.8 kg placebo; METAOD005, n=300) but the pivotal 24-week OPTIONS trial (METAOD006, n=536) failed to show statistically significant weight loss. Development was discontinued in February 2007. Even the modified, more stable, more potent analog did not produce sufficient clinical weight loss for regulatory approval.
WADA explicitly prohibits both compounds by name under S2 (Growth Hormone Fragments). This makes GH Fragment 176-191 one of the few research chemicals explicitly named on the Prohibited List, not merely covered by general catch-all language. Any competitive athlete using this compound faces a potential multi-year anti-doping suspension.
Human growth hormone (HGH) is a 191-amino-acid peptide produced by the anterior pituitary gland with multiple physiological effects mediated through the growth hormone receptor. The somatogenic and lipolytic properties of growth hormone were long known to be separable, and in the 1990s Professor Frank Ng at Monash University (Melbourne, Australia) identified the C-terminal region spanning amino acids 176 to 191 as the region responsible for much of growth hormone's lipolytic activity.
This 16-amino-acid fragment, beginning with phenylalanine at the N-terminus, could stimulate fat oxidation and inhibit lipogenesis in vitro and in animal models without binding the growth hormone receptor or stimulating IGF-1 production. Metabolic Pharmaceuticals then modified the fragment by substituting tyrosine for phenylalanine at position 176, creating AOD-9604 (Anti-Obesity Drug 9604). This modification improved stability and enhanced lipolytic potency. AOD-9604 was advanced through clinical development; the unmodified fragment was never taken forward into human trials.
The unmodified GH Fragment 176-191 subsequently became widely traded as a research chemical by vendors who frequently conflate it with AOD-9604, referencing the METAOD clinical trial data as if it applied to both compounds. It does not. The two peptides have distinct identities and distinct evidence bases.
GH Fragment 176-191 stimulates lipolysis (triglyceride hydrolysis to free fatty acids and glycerol) and inhibits lipogenesis (de novo fatty acid synthesis) in adipose tissue, through a pathway that does not involve the growth hormone receptor.
The growth hormone receptor requires two distinct binding sites on the HGH molecule for functional activation. GH Fragment 176-191 corresponds to the C-terminal region that lacks the structural elements required for both binding events and therefore cannot activate the GH receptor. This was confirmed experimentally: neither the unmodified fragment nor AOD-9604 competed for GH receptor binding or induced proliferative signaling via the GH receptor in transfected cell systems.
The lipolytic mechanism without GH receptor activation involves at minimum the beta-3 adrenergic receptor pathway: AOD-9604 studies in beta-3-AR knockout mice showed that chronic weight-loss effects were absent in knockouts while acute fat oxidation was preserved, suggesting both beta-3-AR-dependent and independent components. AOD-9604 also increased beta-3-AR mRNA expression in obese mice to levels seen in lean mice, suggesting a restoration of downregulated lipolytic receptor expression in obese adipose tissue. The primary receptor mediating acute fat oxidation in the absence of beta-3-AR has not been identified.
Separately from lipolytic stimulation, the fragment inhibits lipogenic enzymes, reducing new fat synthesis. This dual action (increased breakdown + decreased synthesis) distinguishes it from agents that only stimulate lipolysis.
Because all mechanistic studies at the molecular level used AOD-9604 or very closely related synthetic fragments, the specific mechanistic contributions of the unmodified GH Fragment 176-191 are assumed by structural similarity rather than directly established.
Heffernan 2001 (obese mice, 14 days): AOD-9604 (the modified fragment) significantly reduced body weight gain and increased fat oxidation in ob/ob obese mice. Effects associated with increased plasma glycerol (lipolysis) but not with hyperglycemia or reduced insulin. GH receptor competition was absent. The unmodified GH Fragment 176-191 was characterized in parallel mechanistic studies as having comparable lipolytic properties in vitro.
Phase IIb METAOD005 (n=300 obese subjects, 12 weeks, AOD-9604): At the 1 mg/day dose, subjects receiving AOD-9604 lost an average of 2.6 kg versus 0.8 kg in the placebo group, a statistically significant difference of 1.8 kg. This is the most favorable efficacy result in the clinical program.
Phase IIb METAOD006 OPTIONS (n=536 obese subjects, 24 weeks, AOD-9604): At all three dose levels tested (0.25, 0.5, and 1 mg/day), weight loss compared to placebo was not statistically significant. Metabolic Pharmaceuticals announced February 2007 that results 'do not support the commercial development of AOD9604.' Development was discontinued.
Stier 2013: Across six trials and 925 subjects, AOD-9604 showed no serious adverse events, no IGF-1 changes, and no glucose disruption.
The preclinical fat oxidation evidence is robust in animal models. The clinical evidence for the modified analog AOD-9604 showed a modest 12-week signal that did not replicate in the larger 24-week trial. This is the honest picture: a biologically real mechanism in animals that did not translate to commercially meaningful weight loss in humans. GH Fragment 176-191 itself has zero human clinical data. Citing AOD-9604's 1.8 kg 12-week result as evidence for the unmodified fragment's efficacy requires two inferential jumps (the modified to unmodified, and the 12-week to any-duration), neither of which is supported by published data.
The mechanistic advantage of GH fragment over full-length growth hormone for fat loss applications is genuine at the molecular level: the fragment retains lipolytic activity while lacking the two structural elements (binding sites 1 and 2) required for GH receptor activation. This eliminates IGF-1 elevation, insulin resistance, tissue growth promotion, and the proliferative risk associated with sustained GH receptor signaling.
Stier 2013 confirmed across 925 human subjects receiving AOD-9604 that IGF-1 levels remained unchanged at all dose levels in all trials. Fasting glucose and insulin sensitivity were unaffected. No growth-related adverse effects were documented. This clean metabolic profile distinguishes the fragment from full-length growth hormone.
The mechanistic case is solid: the fragment is genuinely selective for lipolysis and does not activate the GH receptor. The safety advantage over full-length growth hormone is real. The limitation is that this selectivity, while scientifically interesting, did not produce clinically meaningful fat loss in the pivotal human trial of the modified analog. For competitive athletes seeking fat loss, neither the safety profile advantage nor the preclinical mechanism translates to an approved or evidence-validated treatment, and WADA prohibits both compounds explicitly.
WADA's Prohibited List under S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics) explicitly names both 'AOD-9604' and 'hGH 176-191' as examples of prohibited growth hormone fragments. This is one of the rare cases where an unpatented, non-pharmaceutical research chemical is named explicitly on WADA's list rather than relying on general catch-all language covering substance classes.
Anti-doping laboratories have developed and validated LC-MS/MS analytical methods capable of detecting these fragments in urine and blood matrices and distinguishing them from each other and from full-length growth hormone. The detection methodology has been peer-reviewed and published.
There is no therapeutic use exemption pathway for either compound since neither has an approved therapeutic indication in any jurisdiction.
The anti-doping status is unambiguous. Both names are on the WADA Prohibited List. Any competitive athlete using GH Fragment 176-191 faces a potential multi-year anti-doping suspension. This has been the case since 2013. No change is expected given that neither compound has advanced toward pharmaceutical approval.
Following the failure of the AOD-9604 obesity program in 2007, Metabolic Pharmaceuticals pivoted to investigating GH fragment activity in cartilage repair. Preclinical models showed improved repair of cartilage defects in animals treated with GH fragment versus controls. In 2009, Metabolic Pharmaceuticals and Phosphagenics Limited signed a collaboration agreement to explore AOD-9604 and GH fragment for osteoarthritis and cosmetic applications.
No human clinical trial of either GH Fragment 176-191 or AOD-9604 in osteoarthritis or cartilage repair has been published. The collaboration agreement has not resulted in any published clinical trial data as of March 2026.
Preclinical cartilage data exists and the mechanism is plausible (GH has documented cartilage effects; the fragment may preserve these while avoiding systemic GH side effects). However, 16 years after the osteoarthritis pivot, no human clinical trial has been published. This application remains at the preclinical hypothesis stage.
Similar lipolytic mechanism to AOD-9604. 250-500mcg before fasted cardio typical.
GH Fragment 176-191 has no validated human pharmacokinetic or dosing data. The numeric dose values above are from research chemical community consensus extrapolated from AOD-9604 (which is a distinct compound). AOD-9604 was studied at 0.25 to 30 mg/day in oral Phase IIb trials. The unmodified fragment is expected to be less stable and potentially less potent than AOD-9604 per unit dose. No pharmacokinetic study of the unmodified fragment in humans exists.
GH Fragment 176-191 is the parent compound from which AOD-9604 (order 33) was derived. AOD-9604 has an N-terminal tyrosine instead of phenylalanine, improved stability, and the entire clinical trial evidence base. For any practical research, AOD-9604 is the more appropriate compound. GH Fragment 176-191 is sometimes sold alongside or instead of AOD-9604 by research chemical vendors, and clinical data from the METAOD program is frequently misattributed to the unmodified fragment. The two peptides are not interchangeable from an evidence standpoint. Both are WADA-prohibited. The broader context for this class: even AOD-9604, after six human trials and 925 subjects, could not demonstrate sufficient clinical weight loss for regulatory approval. GH Fragment 176-191 starts from behind that starting line.
The safety profile of GH Fragment 176-191 specifically has not been formally characterized in humans. The human safety data for this peptide class belongs entirely to AOD-9604.
Stier et al. (2013) reviewed all six METAOD trials involving approximately 925 subjects who received AOD-9604 in various doses and routes (intravenous and oral) over periods up to 24 weeks. No serious adverse events were reported in any trial. No changes in IGF-1 levels, fasting glucose, or other metabolic markers were observed at any dose. The most common adverse events were mild and transient, consistent with general injectable peptide or oral capsule tolerability (headache at high oral doses, mild injection site reactions). This favorable safety record applies to AOD-9604.
In December 2024, FDA declined to add AOD-9604 to the 503A Bulks List that authorizes compounding pharmacies to prepare compounds for human administration. The stated reasons included limited long-term safety data, potential for peptide impurities in compounded preparations, and potential immunogenicity. These concerns about compounded peptide quality and long-term human safety data apply equally to the unmodified GH Fragment 176-191, which has even less safety characterization.
In animal models, both the unmodified fragment and AOD-9604 showed no significant toxicity at lipolytic doses. The absence of GH receptor activation eliminates the hyperglycemia, insulin resistance, IGF-1 elevation, and growth-promoting adverse effects associated with full-length growth hormone therapy.
GH Fragment 176-191 is a lipolytic peptide with genuine preclinical biology but no human clinical data of its own. Its modified analog AOD-9604 (profiled separately at order 33) advanced through six human trials involving 925 subjects, found a modest 12-week weight loss signal, failed in the 24-week pivotal trial, and was discontinued in 2007. The unmodified fragment never reached human clinical development.
The most important practical information: when research chemical vendors or community sources cite 'clinical data' for GH Fragment 176-191, they are almost always citing AOD-9604 trial data. These are different compounds. The clinical trial safety record and the efficacy signal (and the pivotal failure) all belong to AOD-9604.
Both compounds are explicitly prohibited by WADA. Neither is FDA-approved or available through compounding pharmacies. The FDA specifically excluded AOD-9604 from its compounding list in December 2024 citing limited safety data, impurity concerns, and immunogenicity risk.
For competitive athletes: unambiguous prohibition since 2013, both compounds named. For biohackers interested in fat loss: the clinical story for the better-studied analog ended with a pivotal trial failure. For researchers interested in the underlying biology: the mechanism is genuinely interesting and the cartilage application remains unexplored at the clinical level.
For research and educational purposes only · Not medical advice · Consult a qualified physician before any human use