RESEARCH PROFILE
AOD-9604
Synthetic Human Growth Hormone Fragment
AOD-9604 is a synthetic peptide derived from the C-terminal region of human growth hormone. It was developed to investigate whether metabolic effects associated with this region of growth hormone could be separated from the broader growth-promoting effects of the full hormone.
INVESTIGATIONAL • NOT FDA APPROVED • LIMITED HUMAN EFFICACY EVIDENCE
AOD-9604 AT A GLANCE
Category
Growth hormone derived metabolic peptide
Also Known As
HGH Fragment 176-191 • Hexadecapeptide 177-191
Structure
16 amino acid synthetic peptide
Research Focus
Fat metabolism • Obesity research
Regulatory Status
Not FDA approved
Human Evidence
Phase 1 and Phase 2 clinical research
AOD-9604 corresponds to the final 15 amino acids of human growth hormone, positions 177 through 191, with an additional tyrosine added to stabilize the molecule.
It was investigated primarily as a potential obesity treatment, with researchers attempting to isolate metabolic effects associated with the C-terminal region of growth hormone without reproducing the broader effects of full length HGH.
Human clinical trials were conducted, but the largest Phase 2b study did not demonstrate a statistically significant weight loss advantage over placebo at its primary endpoint.
WHAT IS AOD-9604?
AOD-9604 is a synthetic peptide derived from the C-terminal region of human growth hormone.
Rather than reproducing the entire 191 amino acid growth hormone molecule, AOD-9604 was designed around the portion of HGH that researchers believed might participate in regulation of fat metabolism.
The peptide contains 16 amino acids. It corresponds to HGH residues 177 through 191 with an additional tyrosine incorporated for molecular stability.
Researchers developed AOD-9604 to investigate whether metabolic effects attributed to this region of growth hormone could occur without the muscle-building, growth-promoting, blood glucose, and IGF-1 effects associated with full length HGH.
AOD-9604 therefore should not be described simply as injectable growth hormone or as equivalent to HGH.
It is a distinct synthetic peptide with its own research history, pharmacology, and evidence limitations.
MECHANISM OF ACTION
AOD-9604 was designed to investigate metabolic signaling associated with the C-terminal region of human growth hormone.
LIPOLYSIS
Preclinical studies reported increased lipolysis, the process through which stored triglycerides are broken down and fatty acids are released.
This has been one of the primary proposed mechanisms underlying interest in AOD-9604 for metabolic research.
LIPOGENESIS
Animal research also reported suppression of lipogenesis, the process involved in formation and storage of new fat.
Together, increased lipolysis and decreased lipogenesis formed the original biological rationale for investigating AOD-9604 in obesity.
BETA 3 ADRENERGIC SIGNALING
Animal experiments suggest that intact beta 3 adrenergic receptor signaling may be involved in AOD-9604's metabolic effects.
In genetically modified mice lacking beta 3 adrenergic receptors, much of the reported fat metabolism effect was lost.
GROWTH HORMONE RECEPTOR
Importantly, available research does not establish AOD-9604 as acting through the growth hormone receptor in the same manner as full length HGH.
FDA's review of the available evidence concluded that AOD-9604's actual mechanism of action remains unknown and that its effects are unlikely to be mediated through the growth hormone receptor. U.S. Food and Drug Administration
WHAT REMAINS UNKNOWN
The specific molecular receptor or target responsible for AOD-9604's proposed effects has not been definitively identified.
For that reason, descriptions of AOD-9604 as a precisely understood “fat burning peptide” go beyond what the current evidence establishes.
WHAT THE RESEARCH SHOWS
HUMAN CLINICAL DEVELOPMENT
AOD-9604 is unusual among many research peptides because it progressed through formal Phase 1 and Phase 2 human clinical research.
Across its development program, approximately 900 participants were exposed to AOD-9604 in controlled clinical studies.
However, having human clinical research does not mean that efficacy was established.
EARLIER OBESITY TRIAL
An earlier randomized clinical study evaluated oral AOD-9604 in approximately 300 adults with obesity.
Several doses were investigated over 12 weeks.
The investigators reported a statistically significant difference in weekly weight loss at the 1 mg dose, while the overall dose response was not straightforward.
These findings helped support continued clinical development but were not sufficient to establish AOD-9604 as an effective obesity treatment.
LARGEST PHASE 2B STUDY
The strongest test of AOD-9604's proposed weight loss effect came from the METAOD005 / OPTIONS Phase 2b trial.
Approximately 502 adults with obesity were randomized to oral AOD-9604 or placebo alongside a supervised diet and exercise program.
Participants received 0.25 mg, 0.5 mg, or 1 mg per day for 24 weeks.
The trial was designed to detect a clinically meaningful difference in body weight compared with placebo.
PRIMARY ENDPOINT NOT MET
The Phase 2b study did not demonstrate a statistically significant weight loss advantage over placebo.
The primary efficacy endpoint was therefore not met, and development of AOD-9604 as an obesity drug was subsequently discontinued.
This is one of the most important pieces of evidence to communicate when discussing AOD-9604.
PRECLINICAL FAT METABOLISM EVIDENCE
Animal studies provide stronger mechanistic signals than the human efficacy data.
Research in obese rodents reported:
Increased lipolysis
Reduced lipogenesis
Reduced weight gain in some models
No apparent increase in plasma glucose or insulin
Dependence of some effects on beta 3 adrenergic signaling
These findings provide biological rationale for continued scientific interest but cannot be assumed to predict meaningful fat loss in humans. FDA's review similarly describes the lipolysis and lipogenesis findings as nonclinical evidence. U.S. Food and Drug Administration
CARTILAGE & JOINT RESEARCH
A separate animal study evaluated intra-articular AOD-9604 in a rabbit osteoarthritis model.
The study reported improvements in some cartilage and lameness measures compared with hyaluronic acid alone.
This was preclinical animal research, not evidence of established joint or cartilage benefits in humans.
IMPORTANT EVIDENCE LIMITATIONS
There is currently:
No FDA approved indication for AOD-9604
No established human subcutaneous treatment protocol
No published human evidence establishing the commonly marketed subcutaneous amounts as clinically effective
No convincing Phase 3 efficacy program establishing weight loss benefit
No established human evidence demonstrating cartilage or joint repair
The largest controlled obesity trial failed its primary efficacy endpoint.
Marketing claims about predictable fat loss, “targeted fat burning,” cartilage regeneration, or other clinical outcomes therefore exceed what the available human evidence establishes.
SAFETY & RESEARCH CONSIDERATIONS
AOD-9604 has more human exposure data than many experimental peptides, but its safety evidence remains incomplete, particularly for routes of administration now commonly marketed outside the original clinical trials.
OBSERVED HUMAN TRIAL EFFECTS
Reported adverse events in human research included:
Headache
Fatigue
Dizziness
Nasopharyngitis
Diarrhea
Flatulence
Increased appetite
Nausea
Back pain
Most reported events were mild or moderate.
However, individual serious or potentially significant findings occurred during development, and the available data do not establish long term safety for current nonapproved uses.
ROUTE OF ADMINISTRATION MATTERS
Published human research primarily investigated oral and intravenous AOD-9604.
FDA's review found no published human pharmacokinetic study adequately characterizing the commonly marketed subcutaneous route.
Therefore, safety and dosing information from oral or intravenous research should not simply be transferred to subcutaneous administration.
IMMUNOGENICITY & PRODUCT QUALITY
FDA has specifically identified potential concerns involving:
Immunogenicity for certain administration routes
Peptide related impurities
Active pharmaceutical ingredient characterization
Limited safety information for proposed compounded routes
FDA states that it lacks sufficient information to determine whether compounded AOD-9604 would cause harm in humans and has identified serious adverse events potentially associated with the substance, although causality is unclear. U.S. Food and Drug Administration
ANIMAL TOXICOLOGY SIGNALS
Animal toxicology studies reviewed in your Project profile identified findings that warrant caution, including changes in serum osteocalcin and liver findings in monkey studies.
These findings do not establish that the same effects occur in humans, but they reinforce the limitations of assuming long term safety.
LIMITED POPULATION DATA
Published human studies primarily involved adults with obesity.
Safety information is especially limited or absent for populations such as:
Pregnant or breastfeeding individuals
Children and adolescents
People with significant liver disease
People with poorly controlled bone turnover disorders
Many patients with active or recent cancer histories
Specific drug interaction studies are also lacking.
REGULATORY CONTEXT
AOD-9604 IS NOT FDA APPROVED
AOD-9604 is not an FDA approved drug or active ingredient in an FDA approved drug product.
It has no FDA approved therapeutic indication.
FDA COMPOUNDING REVIEW
On December 4, 2024, FDA's Pharmacy Compounding Advisory Committee reviewed AOD-9604 free base and AOD-9604 acetate after the substances were nominated for potential inclusion on the 503A Bulks List.
The proposed use evaluated by FDA was obesity. U.S. Food and Drug Administration
FDA's review raised concerns involving characterization of the active pharmaceutical ingredient, peptide related impurities, immunogenicity, limited human safety information for proposed routes, and lack of convincing clinical effectiveness.
CURRENT FDA CATEGORY STATUS
This portion of your Project profile needed a current check because the regulatory status evolved after the 2024 review.
AOD-9604 had previously appeared in FDA's Category 2 framework. FDA's current page now places AOD-9604 among “bulk drug substances nominated but withdrawn.”
FDA nevertheless continues to list the potential safety concerns it identified during review, including immunogenicity, peptide related impurities, API characterization, limited safety information, and serious adverse events of uncertain causality. U.S. Food and Drug Administration
That means the most accurate website language is not simply “AOD-9604 is Category 2.”
Instead:
AOD-9604 is not FDA approved. Its nomination for the applicable compounding list was withdrawn after FDA review, and FDA continues to publish the potential safety concerns identified during that review.
SPORT & ANTI DOPING
AOD-9604 is prohibited under World Anti-Doping Agency rules.
Athletes subject to WADA or other anti-doping regulations should not assume that a substance's availability as a research compound makes it permissible in competition.
GRAS STATUS DOES NOT MEAN DRUG APPROVAL
AOD-9604 has also been associated with a self-affirmed GRAS determination for a limited food ingredient context.
That designation does not constitute FDA approval of AOD-9604 as a therapeutic drug, injectable medication, obesity treatment, or compounded drug product.
Regulatory terminology matters. Research history, GRAS status, and prior clinical trials should not be presented as FDA approval or proof of clinical effectiveness.
ANALYTICAL DOCUMENTATION
Croix maintains available third party analytical documentation for specific samples and lots represented in its research library.
AOD-9604 5 MG
The Croix Project catalog identifies:
AOD-9604 — 5 mg
LOT SPECIFIC ANALYTICAL DOCUMENTATION
Analytical documentation is displayed only when Croix has a corresponding laboratory report that can be matched to the specific product and lot.
No matching AOD-9604 COA is currently displayed.
IMPORTANT COA LIMITATION
When analytical documentation becomes available, results should be presented only for the specific sample and lot identified in the laboratory report.
A Certificate of Analysis for one sample does not establish the composition, purity, sterility, safety, efficacy, or characteristics of another sample, lot, batch, or product.
Croix's Project standard specifically requires matching the product, strength, lot or batch, sample ID, laboratory, and report date before analytical documentation is presented.
SELECTED RESEARCH & REFERENCES
Stier H, et al.
Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans.
Journal of Endocrinology and Metabolism. 2013.
Human safety and tolerability research examining AOD-9604.
Heffernan MA, et al.
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.
Endocrinology. 2001.
Preclinical investigation of fat metabolism and beta 3 adrenergic receptor involvement.
Ng FM, et al.
Metabolic studies of a synthetic lipolytic domain of human growth hormone.
Hormone Research. 2000.
Preclinical investigation of the metabolic properties associated with the C-terminal HGH fragment.
Wells J, et al.
Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model.
Annals of Clinical and Laboratory Science. 2015.
Preclinical cartilage and osteoarthritis research.
U.S. Food & Drug Administration
FDA Evaluation of AOD-9604-Related Bulk Drug Substances.
Pharmacy Compounding Advisory Committee briefing materials. December 2024. U.S. Food and Drug Administration
U.S. Food & Drug Administration
Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks.
Current FDA compounding status and identified safety concerns. U.S. Food and Drug Administration
RESEARCH & EDUCATIONAL INFORMATION
This profile is provided for research and educational reference. It does not constitute individualized medical advice or establish AOD-9604 as safe or effective for personal use.
AOD-9604 is not FDA approved for any therapeutic indication. Although it has undergone human clinical research, its largest Phase 2b obesity trial did not demonstrate a statistically significant weight loss advantage over placebo at the primary endpoint.
Preclinical findings involving fat metabolism, cartilage, or other biological effects should not be interpreted as established clinical benefits in humans.
Analytical documentation presented by Croix applies only to the specific samples and lots identified in corresponding laboratory reports.