AOD-9604 peptide: what it is, trial findings and research (not fragment 176-191)
AOD-9604 is a modified fragment of human growth hormone (16 residues: a tyrosine added to hGH 177-191, with one disulfide bond) studied for lipolysis in obese rodents, oral tolerability in 12- and 24-week trials and effects without growth hormone receptor signaling. PrymaLab supplies it as an AOD9604 5MG vial, an AOD9604 10mg Nasal Spray and a preloaded AOD-9604 pen (6mg).
- Sequence: 16 amino acids, tyrosine followed by hGH residues 177 to 191, with one disulfide bond between two cysteines.
- Class: synthetic C-terminal hGH fragment (hexadecapeptide); not a growth hormone secretagogue and not full hGH.
- Studied for: lipolysis in obese mice, oral tolerability in humans (Stier 2013), and cartilage repair after intra-articular injection in a collagenase-induced knee osteoarthritis model in rabbits (Kwon and Park, 2015).
- Trial designs: oral, placebo-controlled trials of 12 weeks (METAOD005, 300 participants) and 24 weeks (METAOD006, 502 participants); earlier intravenous studies were single-dose.
- Clinical outcome: the 12-week trial reported more weight loss than placebo, the 24-week trial did not repeat it, and obesity development ended in 2007.
- Storage: lyophilized vial refrigerated; reconstituted solution refrigerated and protected from light.
- Forms and sizes at PrymaLab: AOD9604 5MG, AOD9604 10mg Nasal Spray, AOD-9604 pen (6mg), HGH Fragment 176-191 pen.
| Feature | AOD-9604 | HGH fragment 176-191 |
|---|---|---|
| Structure | Tyrosine plus hGH 177-191 (16 residues); the N-terminal phenylalanine of the native fragment is replaced by tyrosine | hGH residues 176-191 as they occur in the hormone (16 residues) |
| Origin | Metabolic Pharmaceuticals (Melbourne), from Monash University work on the lipolytic domain of hGH; the tyrosine allowed radiolabelling | Native C-terminal sequence of hGH |
| Human trials | Oral trials METAOD004 to METAOD006, up to 502 participants over 24 weeks | No published human trial |
| Forms at PrymaLab | AOD9604 5MG, AOD9604 10mg Nasal Spray, AOD-9604 pen | HGH Fragment 176-191 pen (10mg) |
The peptide reconstitution calculator converts the 5 mg vial into mcg per unit volume. For the other compounds studied in this area, see the peptides and weight loss guide.
Also known as: AOD9604, AOD 9604, Tyr-hGH(177-191)
Quick answer: AOD 9604 peptide
AOD-9604 is the C-terminal lipolytic region of human growth hormone, residues 177 to 191, with a tyrosine added at the N-terminus so the fragment could be radiolabelled during early tracer work. It has been through placebo-controlled human trials: METAOD005 (300 participants, 12 weeks) and METAOD006 (502 participants, 24 weeks) confirmed oral tolerability. The 12-week trial reported weight loss beyond placebo, with the sponsor citing an average 2.8 kg in one dose group against 0.8 kg on placebo, but the larger 24-week trial did not repeat that result and obesity development was stopped in 2007. This guide covers the structure, the lipolysis data, what each trial measured and how it differs from the unmodified fragment 176-191; the peptides and weight loss guide covers the wider field, and the peptide reconstitution calculator converts the 5 mg vial into mcg per unit volume. PrymaLab supplies the AOD9604 5MG vial, an AOD9604 10mg Nasal Spray and a preloaded AOD-9604 autoinjector pen for research use only.
A research summary of AOD 9604, a fragment of human growth hormone studied in six human clinical trials, a rabbit cartilage study, and a GRAS assessment for food use. It covers the science and the evidence.
If you have been researching peptides for weight loss, you have almost certainly met aod-9604. Originally developed as an anti-obesity drug candidate by Professor Frank Ng and colleagues at Monash University, this peptide fragment has progressed through six human clinical trials involving roughly 893 participants — a level of clinical scrutiny rare among research peptides.
The AOD 9604 peptide literature extends beyond fat loss: a rabbit study reported effects on cartilage, human trials of up to 24 weeks reported a safety profile similar to placebo, and its proposed mechanism differs from both growth hormone therapy and the GLP-1 agonists.
This guide unpacks everything the published science actually says about AOD 9604 — its cell-level mechanism, fat-body function effects, joint health possible, clinical safety data, and how it compares to other fat loss peptides and modern weight loss drugs. You will find every claim traced back to its original source.
What is AOD 9604 peptide?
AOD 9604 — an abbreviation for Advanced Obesity Drug, serial number 9604 — is a synthetic peptide consisting of 16 amino acids that correspond to amino acids 177-191 of the C-terminal region of human growth hormone, with an extra tyrosine residue attached at the N-terminal end for peptide stabilization (Ogru et al., 2000, J Pept Res).
Its amino acid sequence reads YLRIVQCRSVEGSCGF, and the molecule is cyclized through a disulfide bond between its two cysteine residues, giving it a three-dimensional conformation that closely mirrors the same region within the intact, 191-amino-acid hGH molecule.
The growth of aod-9604 peptide arose from a simple but powerful finding: human growth hormone regulates fat body function through a specific domain located at its carboxy terminus, entirely separate from the domains responsible for IGF-1 boost, tissue growth, and diabetogenic effects. In the early 1990s, Professor Frank Ng and colleagues at Monash University in Melbourne, Australia, began systematically synthesizing and testing C-terminal hGH fragments to isolate the fat-metabolizing region.
Their work identified amino acids 177–191 as the key lipolytic domain — a segment that increased fat breakdown and reduced fat formation in their experiments without the metabolic side effects linked with full-length growth hormone therapy (Wu & Ng, 1993, Biochem Mol Biol Int; Ng et al., 2000, Horm Res).
What makes this peptide scientifically notable is what it deliberately cannot do. Full start of the hGH receptor needs one intact growth hormone molecule to sequentially bind two receptor molecules at two distinct binding sites, forming a trimer that starts downstream signal transduction. AOD 9604 partially overlaps with binding site 1 (located in the fourth helix of hGH) but completely lacks binding site 2.
Competition binding assays in cells transfected with the hGH receptor have confirmed that AOD 9604 cannot compete with hGH for receptor binding, and BaF3 cell proliferation tests showed that even at very high levels, AOD 9604 does not induce cell proliferation (Heffernan et al., 2001, Int J Obes). This structural limitation is the proposed reason AOD 9604 lacks the growth-promoting effects of the full hormone.
C-terminal fragments before AOD-9604
Work on the C-terminal end of human growth hormone began well before AOD-9604. In 1978 Ng and Bornstein synthesised peptides matching hormone residues 172-191, 176-191, 177-191, 178-191, 179-191 and 180-191 and tested them in normal rats (Ng et al. 1978). The four longest, from 172-191 down to 178-191, produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin, while 179-191 and 180-191 were inert (Ng et al. 1978). Peptides containing the 178-191 sequence also lowered insulin sensitivity in intravenous insulin tolerance tests (Ng et al. 1978). The authors concluded that an active peptide needed the minimum sequence and also the correct physical configuration (Ng et al. 1978).
That early picture was hyperglycaemic, the opposite of what the later AOD-9604 papers reported. In obese Zucker rats, AOD-9604 showed no adverse effect on insulin sensitivity by euglycaemic clamp, unlike chronic treatment with intact growth hormone (Ng et al. 2000), and in obese mice it did not cause hyperglycaemia or lower insulin secretion (Heffernan et al. 2001). The 1978 tests were acute, in normal rats, and used native sequences, including 176-191 and 177-191; the later work was chronic, in obese animals, and used the tyrosine analogue. The abstracts do not explain the difference, and the two sets of results are best read side by side, with neither assumed to cancel the other.
How AOD 9604 works: the lipolysis findings
The mechanism of action behind the AOD 9604 peptide is why researchers consider it different from both traditional hGH therapy and appetite-based weight loss drugs. In the studies below, AOD 9604 increased fat breakdown and reduced new fat formation in fat cells and obese rodents, without engaging the growth hormone receptor or the insulin-like growth factor-1 (IGF-1) signaling axis.
Stimulating Lipolysis: Breaking Down Stored Fat
The first arm of AOD 9604’s mechanism involves boosting lipolysis and fat mobilization — the biochemical process by which triglycerides stored within adipocytes (fat cells) are hydrolyzed into glycerol and free fatty acids, which then enter the bloodstream for energy use. In genetically obese mice (ob/ob model), chronic AOD 9604 treatment greatly increased fat oxidation rates and reduced cumulative body weight gain without affecting lean mass, food intake, or water consumption (Heffernan et al., 2001, Int J Obes).
In that study the lipolytic effect was comparable in magnitude to that produced by full-length hGH.
Research using beta-3-adrenoreceptor knockout mice revealed an important mechanistic detail: AOD 9604 appears to partially exert its lipolytic effects by upregulating beta-3 adrenergic receptors (beta-3-AR) RNA expression in adipose tissue. In normal obese mice, chronic AOD 9604 treatment increased repressed beta-3-AR mRNA levels — a receptor subtype of beta-3 adrenergic receptors critically involved in fat cell lipolysis — while in beta-3-AR knockout animals, the fat-reducing effects of AOD 9604 were greatly attenuated (Heffernan et al., 2001, Endocrinology). This suggests the beta-3 adrenergic pathway is an important, though likely not exclusive, mediator of AOD 9604’s lipolytic activity.
Inhibiting Lipogenesis: Blocking New Fat Storage
The second arm involves blocking lipogenesis — the pathway through which the body converts excess calories into stored fat. AOD 9604 suppresses acetyl-CoA carboxylase activity in both adipocytes and hepatocytes (Ng et al., 2000, Horm Res). Acetyl-CoA carboxylase is the rate-limiting enzyme in fatty acid biosynthesis; by blocking this enzyme, AOD 9604 effectively slows the production of new fatty acids from dietary substrates.
In these models, AOD 9604 acted on both fat breakdown and fat synthesis.
What benefits are reported for AOD 9604 in the literature?
The evidence base for AOD 9604 spans more than two decades of research, from early in vitro studies at Monash University through Phase IIb human clinical trials with hundreds of participants. Three distinct benefit categories emerge from the published literature, each supported by different levels of evidence.
Fat Metabolism and Weight Loss
The main use driving AOD 9604 growth has always been fat body function, and this is where the strongest lab evidence resides. In chronically treated obese mice, AOD 9604 produced body effects equivalent to those of intact hGH about energy balance and fat oxidation, reducing cumulative body weight gain and adipose tissue mass over treatment periods of several weeks (Natera et al., 1994, Biochem Mol Biol Int; Heffernan et al., 2000, Am J Physiol Endocrinol Metab). Critically, these fat-reducing effects occurred in obese but not lean animal models, suggesting the peptide preferentially targets pathological fat buildup rather than disrupting normal adipose homeostasis.
In human trials, the picture is more nuanced. The Phase IIb study METAOD005 — a double-blind, placebo-controlled trial across five Australian hospitals with 300 obese participants given oral AOD 9604 at several dose levels or placebo for 12 weeks — and the larger METAOD006 study with 502 participants over 24 weeks both confirmed safety and tolerability. Weight loss effects were saw in earlier, smaller trials but were less pronounced in the final large study, which incorporated an intensive diet and exercise regime for all participants including the placebo group.
When weight loss was saw in earlier trials, it was similar in magnitude and distribution to that seen with full-length hGH in published studies — very targeting abdominal fat (Moré & Kenley, 2014, J Endocrinol Metab).
| Study | Participants | Route | Duration | Key Finding |
|---|---|---|---|---|
| Heffernan 2001 | Obese mice (ob/ob) | Chronic treatment | Several weeks | Reduced body weight, increased fat oxidation; no IGF-1 or glucose changes |
| METAOD001 (Phase I) | 15 healthy males | Intravenous | Single dose | Well tolerated; safety profile comparable to placebo and rhGH |
| METAOD002 (Phase IIa) | 23 obese males | Intravenous | Single dose | No clinically relevant changes in glucose, IGF-1, or safety labs |
| METAOD005 (Phase IIb) | 300 obese adults | Oral | 12 weeks | Safe; no IGF-1 changes; trend toward improved glucose tolerance |
| METAOD006 (Phase IIb) | 502 obese adults | Oral | 24 weeks | Safety indistinguishable from placebo over 6 months |
Cartilage findings in a rabbit osteoarthritis model
AOD 9604 has also been studied in a joint model. A 2015 study by Kwon and Park at the Catholic University of Daegu examined the effects of intra-articular AOD 9604 injections in a collagenase-induced knee osteoarthritis rabbit model (Ann Clin Lab Sci, 2015;45(4):426-32). Thirty-two rabbits got weekly injections of either saline, hyaluronic acid (HA) alone, AOD 9604 alone, or the mix of AOD 9604 with HA for four to seven weeks following osteoarthritis induction.
Both AOD 9604 alone and the combination produced significantly lower gross morphological and histopathological degeneration scores than the saline control in this model. Most notably, the AOD 9604 plus HA mix was greatly more effective than either treatment alone, yielding the lowest degeneration scores and the shortest lameness period among all groups. This combined effect suggests that AOD 9604 addresses a regrowth pathway that complements the viscosupplementation and anti-swelling properties of hyaluronic acid.
These joint findings come from one rabbit study.
No human trials have been conducted mainly for AOD 9604 in osteoarthritis, and the rabbit model, while informative, has known limitations in predicting human joint outcomes.
Metabolic Safety Advantages Over Full-Length hGH
A central question for AOD 9604 was whether it avoided the metabolic effects of growth hormone. Full-length human growth hormone therapy, while effective for fat reduction, carries a well-documented list of body liabilities: glucose intolerance, insulin resistance, increased diabetes risk, elevated IGF-1 with linked cancer risk, sodium retention with edema, and acromegalic features with long-term use (Baumann, 1999; Cameron et al., 1987; Scacchi et al., 1999). These side effects have historically limited hGH’s utility as a weight care tool.
AOD 9604 was designed to avoid these effects. Across six human clinical trials with about 893 participants, AOD 9604 produced no changes in serum IGF-1 levels, no impairment of glucose tolerance on oral glucose tolerance testing (OGTT), no evidence of insulin resistance, no clinically major changes in any safety laboratory parameters, vital signs, or electrocardiograms, and no generation of anti-AOD9604 antibodies at any time point up to 24 weeks of treatment (Stier et al., 2013, J Endocrinol Metab).
Notably, there was actually a trend toward improved glucose tolerance and blood sugar management in AOD 9604 treatment groups, with patients who had impaired glucose tolerance at baseline being less likely to progress to diabetes compared to placebo recipients.
How AOD 9604 compares with GLP-1 agonists and other fat loss peptides
The modern weight loss landscape has been transformed by GLP-1 receptor agonists like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound)alongside growth hormone secretagogues like tesamorelin. Grasp where AOD 9604 fits within this evolving toolkit needs an honest comparison of mechanisms, evidence levels, and practical factors.
| Feature | AOD 9604 | Semaglutide (GLP-1) | hGH (Somatotropin) | CJC-1295/Ipamorelin |
|---|---|---|---|---|
| Mechanism | Direct lipolysis + lipogenesis inhibition | Appetite suppression via incretin pathway | Full metabolic activation via hGH receptor | Stimulates endogenous GH release |
| Primary Target | Fat cells (adipocytes) | Brain appetite centers + GI tract | Multiple tissues systemically | Pituitary gland |
| IGF-1 Impact | None (confirmed in 6 trials) | None | Significant elevation | Moderate elevation |
| Glucose Effects | Neutral to improved | Improved (FDA-approved for T2D) | Impaired tolerance / insulin resistance | Variable |
| Appetite Effects | None | Strong suppression | Variable | May increase appetite |
| Human Trial Data | Phase IIb (893 participants) | Phase III + FDA approved | Extensive (FDA-approved indications) | Limited clinical data |
| FDA Status | Not approved; GRAS for foods | FDA approved | FDA approved | Not approved |
| Muscle Preservation | Favorable (no lean mass loss observed) | Moderate muscle loss (25–40% of weight lost) | Favorable | Favorable |
| Joint Benefits | Preclinical cartilage regeneration data | Indirect (weight reduction) | Can worsen joint symptoms | No direct evidence |
| Common Side Effects | Mild headache, local redness | Nausea, vomiting, GI distress | Edema, joint pain, insulin resistance | Flushing, headache |
The comparison reveals that AOD 9604, tesamorelin, and GLP-1 agonists address weight care through entirely paired mechanisms. GLP-1 drugs act as a brake on appetite, reducing caloric intake by an estimated 20–30% through central satiety signals and delayed gastric emptying. AOD 9604 acts as an accelerator on fat body function, directly instructing adipocytes to release stored energy and blocking de novo lipogenesis.
These are differences in mechanism, not results from combined use; the trial evidence for AOD 9604 is summarised in the table above.
However, intellectual honesty demands acknowledging the evidence gap. GLP-1 agonists have Phase III data in tens of thousands of patients, FDA approval, and showed weight loss of 15–20% of body weight. AOD 9604 has Phase IIb data confirming safety but with more modest and inconsistent effect signals. The peptide’s clinical growth stalled after the METAOD006 trial, and no Phase III effect trial has been conducted.
The AOD 9604 trial record supports oral tolerability and a distinct mechanism; it did not show consistent weight loss.
What the AOD 9604 trials measured
AOD 9604 was never advanced to Phase III trials, so no approved use exists. Six human clinical trials tested it: single-dose intravenous studies (METAOD001 in 15 healthy males, METAOD002 in 23 obese males) and oral placebo-controlled trials, including the 7-day METAOD004 study, the 12-week METAOD005 trial in 300 obese adults and the 24-week METAOD006 trial in 502 obese adults. The trials measured tolerability, adverse events, serum IGF-1, glucose tolerance, anti-drug antibodies and body weight (Stier et al., 2013).
All tested doses were reported as well tolerated, though gut side effects including diarrhea and flatulence were more common at the highest oral dose in the 7-day METAOD004 study (Stier et al., 2013). No human injection trial has been published, and this page does not reproduce the regimens that clinics and forums circulate. PrymaLab supplies AOD-9604 for laboratory research only.
Handling AOD 9604 in the lab
AOD 9604 arrives as a freeze-dried powder that is dissolved in a suitable sterile diluent before laboratory use. Careful mixing technique is essential for keeping peptide integrity. Concentration is the peptide mass divided by the diluent volume: a 5 mg vial dissolved in 2.5 mL gives 2 mg/mL.
An AOD-9604 nasal spray skips this entire procedure. It is supplied as a metered aqueous solution, so there is no vial to reconstitute and no concentration to calculate, at the cost of not being able to choose either.
Dissolving and storing the peptide
- Clean the vial top: Swab the rubber stopper with alcohol and allow it to air dry.
- Add the diluent gently: Let the diluent run down the glass wall rather than directly onto the powder. Never shake the vial; AOD 9604 is a fragile peptide.
- Dissolve by swirling: Gently roll the vial until the powder fully dissolves. The solution should be clear and colorless. If it appears cloudy or contains particles, do not use it.
- Store properly: Store the reconstituted solution in the refrigerator at 2–8°C. Do not freeze reconstituted peptide.
Is AOD 9604 safe? What the clinical trial evidence shows
Among research peptides, AOD 9604 has one of the most full safety datasets available — a distinction that sets it apart from the vast most of compounds sold in the peptide marketplace. The safety evidence spans genotoxicity screening, chronic animal toxicology, and six human clinical trials.
Preclinical Safety Data
Before entering human trials, AOD 9604 underwent extensive non-clinical safety testing as summarized by Moré and Kenley (2014, J Endocrinol Metab). The genotoxicity battery included a bacterial reverse mutation test (Ames test), an in vitro chromosome aberration assay in CHO cells, and a bone marrow micronucleus assay — none showed evidence of mutagenic or clastogenic activity.
Chronic toxicology studies included a 6-month rat oral gavage study and a 9-month cynomolgus monkey oral gavage study. The no-observed-adverse-effect level (NOAEL) was the highest dose tested in both species.
Pharmacokinetic studies in pigs confirmed that orally gave AOD 9604 is absorbed with about 40% uptake, undergoes rapid sequential N-terminal amino acid breakdown (plasma half-life of about 3 minutes after IV injection), and distributes to all non-CNS tissues with principal localization in the pancreas, pineal body, thyroid, liver, and kidney cortex.
Importantly, AOD 9604 did not cross the blood-brain barrier in rat whole-body radiography studies, and no anti-AOD9604 antibodies were detected in any animal study, confirming the peptide is not immunogenic.
Human Clinical Trial Safety Summary
The human safety dataset covers about 893 participants across six randomized, double-blind, placebo-controlled trials conducted between 2001 and 2006. The key safety findings are consistent and unambiguous:
- IGF-1 Levels: No significant changes in serum IGF-1 at any dose or time point in any trial, confirming AOD 9604 does not activate the hGH/IGF-1 growth axis.
- Glucose Metabolism: Oral glucose tolerance testing showed no impairment of glucose handling. A trend toward improved glucose tolerance was observed in AOD 9604 groups, with participants having impaired glucose tolerance at baseline being less likely to progress to diabetes.
- Immunogenicity: No anti-AOD9604 antibodies were detected at any time point up to 24 weeks of treatment.
- Adverse Events: The adverse event profile was indistinguishable from placebo. No treatment-related withdrawals or serious adverse events occurred in any trial.
- Vital Signs and ECG: No clinically significant changes in blood pressure, heart rate, body temperature, or electrocardiogram parameters.
- Laboratory Parameters: No clinically significant changes in hematology, blood chemistry, or urinalysis.
AOD 9604 side effects reported in trials
The most often reported AOD 9604 side effects in clinical trials were mild and equally distributed between AOD 9604 and placebo groups, suggesting they may not be directly attributable to the peptide itself.
Documented Side Effects (from clinical trials)
Across all six human studies, the most often reported adverse events included headache (the most common event, reported at similar rates in both treatment and placebo groups), mild gut symptoms including diarrhea and flatulence (particularly at the highest oral dose tested), mild euphoria during IV use in a small number of subjects, and local reactions including transient redness and minor discomfort.
No dose-response relationship for adverse events was identified across the oral dose range tested, and the overall adverse event profile was consistently described as “indistinguishable from placebo” by study investigators (Stier et al., 2013).
What the safety data do not cover
AOD 9604 has not been tested in pregnant or breastfeeding women, and its effects on fetal growth are unknown. Its long-term effects on cell proliferation have not been studied in humans beyond 24 weeks.
People with severe hepatic or renal impairment were excluded from clinical trials, so safety in these populations is uncharacterized, and no drug interaction studies have been published.
Legal status and regulatory position
The control status of AOD 9604 is complex and evolving. It got “Often Recognized As Safe” (GRAS) status from a qualified expert panel for intended use in foods, drinks, and dietary supplements — a designation based on the extensive non-clinical and clinical safety data described above. However, GRAS status for food use does not equate to FDA approval as a pharmaceutical drug.
AOD 9604 is not FDA-approved for any treatment sign and remains classified as an unapproved compound when marketed for disease treatment or prevention. The FDA’s Pharmacy Compounding Advisory Committee (PCAC) has reviewed AOD 9604 in the context of bulk drug substances used in compounding. The compound’s control trajectory remains uncertain, with advocacy groups having submitted detailed safety dossiers to the FDA arguing for its inclusion on the approved compounding substances list.
In practice, AOD 9604 is often available through research peptide suppliers as a “research chemical” or through compounding pharmacies in jurisdictions where it is permitted. Purity, potency, and manufacturing quality can vary greatly between suppliers, making source check critically important. Always verify current regulations in your specific jurisdiction before buying, and check that the certificate of analysis matches the lot number on your vial and can be verified. PrymaLab tests every lot in its own laboratory (RP-HPLC purity, LC-MS identity), and its certificates can be checked at prymalab.net/testing/verify.
Frequently asked questions about AOD 9604
Is AOD-9604 the same as HGH fragment 176-191?
No. HGH fragment 176-191 is the natural C-terminal sequence of growth hormone. AOD-9604 is a modified version: residues 177 to 191 with a tyrosine added at the N-terminus, giving 16 amino acids and one disulfide bond. The tyrosine was added so the fragment could be radiolabelled. AOD-9604 is the version that went through human oral trials (METAOD005, METAOD006); the unmodified fragment has no published human trial.
What is AOD 9604 peptide?
AOD 9604 is a synthetic hexadecapeptide from the lipolytic domain of human growth hormone, studied for fat metabolism without the growth-promoting effects of the full hormone. It does not act on the growth hormone receptor. Developed by Metabolic Pharmaceuticals in Australia, it was tested orally in five-hospital Phase IIb trials. PrymaLab supplies it as an AOD9604 5MG vial, a nasal spray and a preloaded pen.
How were the AOD 9604 trials designed?
METAOD005 gave 300 obese participants oral AOD 9604 or placebo for 12 weeks; METAOD006 ran 24 weeks in 502 participants; METAOD004 was a 7-day study, and its highest dose was the only one linked with more gut side effects (Stier et al., 2013). Earlier intravenous studies were single-dose.
Does AOD 9604 cause weight loss?
In obese mice the fragment increased fat oxidation and reduced weight gain (Heffernan et al., 2001). In humans, the 12- and 24-week oral trials confirmed safety and tolerability. The 12-week trial in 300 obese adults did report weight loss beyond placebo, an average 2.8 kg in one dose group against 0.8 kg on placebo by the sponsor's account, but the 24-week trial in 502 adults did not repeat it and Metabolic Pharmaceuticals stopped obesity development in 2007. The animal lipolysis data and the human outcome data therefore point in different directions.
Is AOD 9604 safe?
The published safety record is unusually deep for a research peptide. Animal toxicology in rats and monkeys set the no-observed-adverse-effect level at the highest doses tested. The oral doses tested in the METAOD trials were well tolerated, with diarrhea and flatulence more common only at the highest dose (Stier et al., 2013). No human injection trial has been published.
- AOD 9604 peptide (Tyr-hGH 177–191, not the native fragment 176–191) is a 16-amino-acid synthetic peptide studied for effects on fat metabolism (lipolysis and lipogenesis) without activating the hGH receptor or the IGF-1 growth axis.
- Clinical safety data from six human trials (~893 participants, up to 24 weeks) demonstrates a profile indistinguishable from placebo — no IGF-1 elevation, no glucose impairment, no insulin resistance, no immunogenicity, and GRAS status for food use.
- Proposed mechanism in obese mice involves beta-3-adrenoreceptor upregulation and acetyl-CoA carboxylase inhibition in adipocytes, with effects seen in obese but not lean animals.
- Cartilage findings come from one rabbit osteoarthritis study, in which AOD 9604 plus hyaluronic acid gave lower degeneration scores than either treatment alone (Kwon & Park, 2015).
- Trial designs: the human efficacy trials used the oral route for up to 24 weeks; no human injection trial has been published.
- Efficacy limitations: Phase IIb trials confirmed safety but showed inconsistent weight loss results.
- Regulatory status is complex: GRAS for food use, not FDA-approved pharmaceutically. Source quality varies significantly, so check that the certificate matches the lot number on your vial and can be verified.
This article is for informational and educational purposes only and does not constitute medical advice. AOD 9604 is not approved by the FDA for any therapeutic indication. The information presented reflects published preclinical and clinical research and academic sources. PrymaLab supplies AOD 9604 for laboratory research use only; it is not for human or veterinary use.
Related reading
- 5-Amino-1MQ: what it is, benefits, dosage and research
- Tesofensine: trials, half-life and approval status
References
- Wu Z, Ng FM. "Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone." Biochem Mol Biol Int. 1993;30(1):187-196. PMID: 8358331.
- Natera SH, Jiang WJ, Ng FM. "Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide." Biochem Mol Biol Int. 1994;33(5):1011-1021. PMID: 7987248.
- Ogru E, Wilson JC, Heffernan M, et al. The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone." J Pept Res. 2000;56(6):388-397. DOI: 10.1034/j.1399-3011.2000.00771.x
- Ng FM, Sun J, Sharma L, et al. "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone." Horm Res. 2000;53(6):274-278. DOI: 10.1159/000053183
- Heffernan MA, Jiang WJ, Thorburn AW, Ng FM. "Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism." Am J Physiol Endocrinol Metab. 2000;279(3):E501-507. PMID: 10950816.
- Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment." Int J Obes Relat Metab Disord. 2001;25(10):1442-1449. DOI: 10.1038/sj.ijo.0801740. PMID: 11673763.
- 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 beta(3)-AR knock-out mice." Endocrinology. 2001;142(12):5182-5189. PMID: 11713213.
- Stier H, Vos E, Kenley D. "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans." J Endocrinol Metab. 2013;3(1-2):7-15. DOI: 10.4021/jem157w
- Moré MI, Kenley D. "Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health." J Endocrinol Metab. 2014;4(3):64-77. DOI: 10.14740/jem213w
- Kwon DR, Park GY. "Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model." Ann Clin Lab Sci. 2015 Summer;45(4):426-32. PMID: 26275694.
- Baumann G. "Growth hormone heterogeneity in human pituitary and plasma." Horm Res. 1999;51(Suppl 1):2-6. DOI: 10.1159/000053128
- Cameron CM, Kostyo JL, Adamafio NA, Dunbar JC. "Metabolic basis for the diabetogenic action of growth hormone in the obese (ob/ob) mouse." Endocrinology. 1987;120(4):1568-1575. DOI: 10.1210/endo-120-4-1568
- Scacchi M, Pincelli AI, Cavagnini F. "Growth hormone in obesity." Int J Obes Relat Metab Disord. 1999;23(3):260-271. DOI: 10.1038/sj.ijo.0800807
- Ng FM, Jiang WJ, Gianello R, et al. "Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats." J Mol Endocrinol. 2000;25(3):287-298. DOI: 10.1677/jme.0.0250287
