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AOD-9604

AOD-9604 is a synthetic 16-amino-acid peptide corresponding to the C-terminal "lipolytic" fragment of human growth hormone (hGH residues 177-191) with an added N-terminal tyrosine (hence also labeled hGH 176-191 or "GH fragment"). It was developed as an oral anti-obesity drug candidate meant to trigger fat breakdown while avoiding growth-hormone-receptor-mediated growth signaling and IGF-1 elevation. Despite heavy marketing as a fat-loss/"body recomposition" and joint-repair peptide, the human evidence is weak and largely negative. Its clinical development was abandoned after a 24-week obesity program (roughly 500 randomized subjects) failed to beat placebo on weight loss, and those conclusions rest on sponsor-reported phase 2 data rather than peer-reviewed randomized trials. It is not approved by any major regulator for any indication, is banned by the World Anti-Doping Agency, and is flagged on the U.S. FDA Category 2 Bulk Drug Substances list over immunogenicity concerns. Most efficacy data are from obese mice and rats, not people. The greatest real-world dangers are therefore not a well-characterized toxicity but the unknowns: no long-term human safety data, no established human pharmacokinetics, unregulated gray-market product of uncertain identity/purity/sterility, and a documented history of counterfeit/mislabeled vials. Anyone using it should do so only under medical supervision with bloodwork, and should understand that claimed fat-loss and cartilage-repair benefits are unproven in humans.

Clinical readoutPeptide · gh-fragment
Hepatic strainLow
CardiovascularNone
HPTA suppressionNone
Half-life
Not reliably esta…
Route
Studied as an oral
Evidence
C
Active
Unknown/not characteriz…
1·t½2·t½3·t½4·t½5·t½
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Not reliably established in humans. As a small unmodified peptide it is expected to have a short plasma half-life (order of minutes to a low number of hours); no validated human half-life has been published in the peer-reviewed literature.
Pharmacology

Mechanism of action

AOD-9604 is derived from the C-terminal lipolytic domain of human growth hormone. In preclinical models it increases fat oxidation and markers of lipolysis and attenuates weight gain in obese mice, and increases lipolytic activity in adipose tissue of obese Zucker rats. Critically, it does not bind or activate the growth hormone receptor and does not induce GH-receptor-mediated cell proliferation, so it does not raise IGF-1 or reproduce the classical somatotropic/growth effects of full-length GH. Its metabolic actions appear to be independent of, but associated with, up-regulation of beta-3 adrenergic receptor expression in fat cells: chronic hGH and AOD-9604 raised beta-3-AR RNA, yet in beta-3-AR knockout mice the chronic weight/lipolysis effect was lost while an acute rise in energy expenditure and fat oxidation persisted, indicating the mechanism is not directly through the beta-3-AR. Unlike full-length GH, it did not cause hyperglycemia or reduce insulin secretion in rodents. Human confirmation of these mechanisms and of any meaningful lipolytic effect in vivo is lacking.
Kinetics

Pharmacokinetics

Half-life

Not reliably established in humans. As a small unmodified peptide it is expected to have a short plasma half-life (order of minutes to a low number of hours); no validated human half-life has been published in the peer-reviewed literature.

Active duration

Unknown/not characterized in humans. Clinical anti-obesity studies used once-daily oral dosing, implying investigators assumed at least a once-daily practical window, but pharmacodynamic duration in humans was not established.

Route

Studied as an oral (p.o.) anti-obesity agent (e.g., 1 mg once daily) and by single intravenous infusion (25-400 micrograms) in early human work; gray-market/off-label use is typically subcutaneous. No route has an approved or validated human PK profile.

Metabolism & clearance

Peptide is proteolytically degraded; in vitro serum/urine incubation identifies multiple metabolites, with a relatively stable fragment (amino acids CRSVEGSCG) used as an anti-doping marker. Renal elimination of parent peptide/metabolites underlies urinary detection. Detailed human clearance/renal-hepatic handling is not characterized. Note: PK is presented here for washout/monitoring context only, not to evade drug testing (AOD-9604 is WADA-banned and detectable).

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • Marketed/intended effect is reduction of body fat via stimulation of lipolysis and fat oxidation, but this has not been demonstrated to produce meaningful weight loss in humans
  • In obese rodents: reduced body-weight gain, increased whole-body fat oxidation, and increased plasma glycerol (an index of lipolysis)
  • In rodents, unlike full-length GH, it did not raise blood glucose or suppress insulin
  • In humans: at most transient, modest metabolic changes reported in some studies, with no meaningful IGF-1 elevation and no consistent, interpretable efficacy signal
  • A 24-week oral obesity program failed to meet its primary weight-loss endpoint versus placebo
  • Claimed cartilage/joint-repair and osteoarthritis benefits are based only on animal work (e.g., intra-articular AOD-9604 with or without hyaluronic acid in a rabbit OA model) and are unproven in humans
  • Does not raise IGF-1 or produce GH-like growth/somatotropic effects (no GH-receptor activation)
Safety

Adverse effects by system

Cardiovascular

No specific cardiovascular toxicity has been documented for AOD-9604 in the limited human data, and no cardiovascular efficacy or safety signal is established. This is an absence of data, not a demonstration of cardiovascular safety; long-term cardiovascular effects in humans are unknown.

Hepatic

No hepatotoxicity has been reported in the available short-term human or animal data, and it is not a recognized hepatotoxin. However, hepatic safety has not been formally studied in humans and cannot be considered established.

Endocrine / HPTA

Mechanistically acts independently of the GH receptor with no meaningful IGF-1 elevation and no systematic somatotropic activation reported; it is not androgenic and is not expected to suppress the hypothalamic-pituitary-testicular/gonadal axis. It is not a steroid or SERM. Long-term human endocrine safety is nonetheless uncharacterized. Theoretical GH/IGF-axis concerns raised for this drug class have not been substantiated for AOD-9604 specifically.

Reproductive

No human reproductive, fertility, pregnancy, or lactation safety data exist. Use in pregnancy/breastfeeding or by those seeking conception is untested and should be avoided.

Neuropsychiatric

No specific psychiatric adverse effects established; mild transient fatigue and headache reported. No adequate human data on neuropsychiatric effects.

Renal

No renal toxicity reported; renal handling contributes to elimination (basis for urinary detection). No adequate human renal safety data.

Hematologic

No hematologic toxicity reported and no adequate human hematologic safety data available.

Dermatologic

Injection-site reactions (pain, redness) reported with subcutaneous off-label use; the compound is flagged for immunogenicity concerns, raising a theoretical risk of allergic/hypersensitivity reactions. No adequate controlled human dermatologic data.

Recovery

HPTA suppression & recovery

Suppression: Not an expected concern. AOD-9604 is not androgenic, acts independently of the GH receptor, and does not meaningfully raise IGF-1 or produce somatotropic activation, so it is not a recognized suppressor of the hypothalamic-pituitary-gonadal axis. Direct long-term human endocrine data are lacking.

Because HPTA suppression is not a described effect of this peptide, no SERM-based post-cycle intervention is indicated on the basis of AOD-9604 use itself. Do not start any SERM or hormonal 'recovery' protocol empirically. Anyone with symptoms of hypogonadism, menstrual disturbance, gynecomastia, or abnormal reproductive hormones (particularly if AOD-9604 was used alongside anabolic-androgenic steroids or other agents) should have this evaluated and managed by an endocrinologist rather than self-treated. If any single-agent SERM is ever considered for a genuine, lab-confirmed endocrine problem, that decision belongs to the treating endocrinologist.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Baseline and periodic fasting glucose and HbA1cFasting lipid panelLiver function tests (AST, ALT, bilirubin)Renal function (creatinine, eGFR)IGF-1 (expected unchanged; useful to confirm no unexpected GH-axis effect)CBCIf used alongside other performance agents or steroids: full hormonal panel (testosterone, LH, FSH, estradiol, prolactin) via a clinician

Cadence: Baseline before any use, then approximately every 8-12 weeks during use and if new symptoms arise; escalate immediately for concerning symptoms. All monitoring should be arranged and interpreted with a physician.

Warning signs — seek care
  • Signs of allergic/hypersensitivity or injection-site reaction (rash, swelling, difficulty breathing) — stop and seek urgent care
  • New or worsening hyperglycemia symptoms (excess thirst, urination, fatigue)
  • Unexplained persistent headache, fatigue, or malaise
  • Any new lump, mass, or rapidly changing skin lesion (prompt oncologic evaluation)
  • Symptoms suggesting contaminated/counterfeit product (fever, injection-site infection, abscess)
  • Endocrine/reproductive symptoms (especially if stacked with steroids): gynecomastia, testicular changes, menstrual disturbance
Do not use if

Contraindications

  • Pregnancy, breastfeeding, or attempting conception (no reproductive safety data)
  • Known hypersensitivity to the peptide or excipients; caution given documented immunogenicity concerns
  • Active or history of malignancy (AOD-9604 lacks GH-receptor/IGF-1 activation, but mitogenic safety in humans is unproven and use should be avoided without oncologic clearance)
  • Use in minors/adolescents (no safety data; growth/developmental effects untested)
  • Reliance on gray-market/counterfeit product of unverified identity, purity, or sterility
  • Use to circumvent anti-doping rules in competitive athletes (WADA-prohibited and detectable)
  • Any use as a substitute for evidence-based obesity treatment, given failed efficacy
Combinations

Interaction profile

  • ContraindicatedWith DNP: Additive cardiovascular strain

Check a specific combination in the interaction checker.

Harm reduction

Reducing harm & when to stop

  • Understand the evidence gap first: AOD-9604's fat-loss and joint-repair claims are unproven in humans; a large obesity program failed, so expectations of meaningful body-fat or weight change are not supported by data.
  • There is no established human pharmacokinetic, long-term safety, reproductive, or carcinogenicity dataset — you are effectively self-experimenting with an abandoned drug candidate.
  • Gray-market product is a major hazard: identity, dose, purity, and sterility are not guaranteed, and AOD-9604 has been found in counterfeit/mislabeled vials. Non-sterile injectable use risks infection and abscess.
  • Do not use as a replacement for evidence-based obesity care (diet, exercise, and, where appropriate, approved medications or bariatric referral supervised by a clinician).
  • If you choose to use it, involve a physician and get baseline plus periodic bloodwork (glucose/HbA1c, lipids, liver and kidney function, IGF-1, CBC).
  • Stop immediately and seek medical care for any allergic reaction, injection-site infection or abscess, persistent unexplained symptoms, or any new lump/mass.
  • Do not stack empirically with steroids, GH, insulin, or other peptides; polypharmacy makes any adverse event harder to attribute and manage, and any endocrine problem should be assessed by an endocrinologist.
  • Avoid entirely if pregnant, breastfeeding, trying to conceive, a minor, or if you have active/prior cancer without specialist clearance.
  • Competitive athletes: AOD-9604 is WADA-prohibited and detectable; this monograph does not support evading testing.
  • This is harm-reduction information, not an endorsement or a protocol; it does not replace individualized medical advice.
Evidence

Citations (13)

Every clinical claim above is tied to a primary source. Overall evidence grade C graded to the best available evidence for its core claims.

  1. 01

    AOD-9604 is a synthetic peptide comprising the C-terminal fragment of human growth hormone (amino acids 177-191) with an additional N-terminal tyrosine residue, sometimes labeled hGH 176-191/GH fragment.

    PreclinicalDetection and in vitro metabolism of AOD9604.DOI 10.1002/dta.1715

  2. 02

    AOD-9604 was developed as an anti-obesity candidate intended to retain GH lipolytic signaling while avoiding GH-receptor-mediated growth effects and IGF-1 exposure; human evidence is limited and a 24-week study (n=534, 502 randomized) failed the primary weight-loss endpoint, based on sponsor-reported phase 2 data rather than peer-reviewed RCTs.

    ReviewThe emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.DOI 10.3389/fendo.2026.1822475

  3. 03

    In humans, at most transient/modest metabolic changes were reported with no meaningful IGF-1 elevation and no systematic somatotropic activation; it was generally well tolerated with mild/transient headache, fatigue, and injection-site reactions and no significant alteration in glucose tolerance or IGF-1; AOD-9604 is unapproved, WADA-banned, and on the FDA Category 2 Bulk Drug Substances list over immunogenicity.

    ReviewThe emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.DOI 10.3389/fendo.2026.1822475

  4. 04

    AOD-9604 is assigned a tier B/C evidence level (short-term human trials exist but with limited interpretable signals; no robust peer-reviewed human efficacy data).

    ReviewThe emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.DOI 10.3389/fendo.2026.1822475

  5. 05

    In obese (ob/ob) mice, chronic hGH and AOD-9604 reduced body-weight gain, increased in vivo fat oxidation and plasma glycerol (lipolysis); unlike hGH, AOD-9604 did not induce hyperglycemia or reduce insulin, did not compete for the GH receptor, and did not induce cell proliferation.

    PreclinicalIncrease of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.DOI 10.1038/sj.ijo.0801740

  6. 06

    The lipolytic actions of hGH and AOD-9604 are not mediated directly through the beta-3 adrenergic receptor, although both increase beta-3-AR expression; chronic weight/lipolysis effects were lost in beta-3-AR knockout mice while an acute rise in energy expenditure/fat oxidation persisted.

    PreclinicalThe 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.DOI 10.1210/endo.142.12.8522

  7. 07

    Oral AOD-9604 in obese Zucker rats reduced body-weight gain by over 50% and increased adipose lipolytic activity with no adverse effect on insulin sensitivity by euglycemic clamp.

    PreclinicalMetabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.DOI 10.1159/000053183

  8. 08

    AOD-9604 is banned by WADA, is detectable in urine, and undergoes proteolytic metabolism yielding a relatively stable fragment (CRSVEGSCG) used as a detection marker.

    PreclinicalDetection and in vitro metabolism of AOD9604.DOI 10.1002/dta.1715

  9. 09

    AOD-9604 does not interfere with the WADA hGH isoform immunoassay, consistent with it not behaving as full-length GH.

    PreclinicalAOD-9604 does not influence the WADA hGH isoform immunoassay.DOI 10.1002/dta.1557

  10. 10

    Claimed cartilage/osteoarthritis benefits derive only from animal work: intra-articular AOD-9604, especially combined with hyaluronic acid, improved cartilage-related outcomes in a collagenase-induced rabbit knee OA model.

    PreclinicalEffect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.PMID 26275694

  11. 11

    AOD-9604 is an unapproved 'gray-market' peptide with scarce rigorous human safety data and potential for serious harm; efficacy is not established in humans.

    ReviewSafety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.DOI 10.1007/s40279-026-02437-0

  12. 12

    AOD-9604 has been identified in seized, unregulated/counterfeit pharmaceutical preparations, underscoring product-identity and purity risk in the gray market.

    Case reportIdentification and characterization of peptide drugs in unknown pharmaceutical preparations seized by the Belgian authorities: case report on AOD9604.DOI 10.1002/dta.1687

  13. 13

    AOD-9604 (Metabolic Pharmaceuticals) was in phase IIa obesity trials as an investigational anti-obesity agent, i.e., never advanced to approval.

    ReviewAOD-9604 Metabolic.PMID 15134286

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice