AOD-9604
A tyrosine-modified fragment of growth hormone engineered to isolate GH's fat-burning action from its growth effects, that cleanly delivered selective lipolysis in trials but failed to produce meaningful weight loss in humans.
AOD-9604 is a synthetic 16-amino-acid peptide corresponding to the C-terminal lipolytic domain of human growth hormone (residues 177-191) with an added N-terminal tyrosine for stability. It was developed by Metabolic Pharmaceuticals (Australia) to reproduce growth hormone's fat-metabolizing activity while avoiding the IGF-1 elevation, glucose intolerance, and tissue growth of full-length GH. Preclinical rodent studies showed lipolysis and fat-mass reduction, and human trials confirmed the selectivity (no IGF-1 rise, clean safety), but the pivotal Phase 2B obesity trial failed to produce statistically significant weight loss versus placebo, and the drug program was discontinued around 2007. It is not approved as a drug anywhere and is sold only as a research compound or, in the US, as a GRAS food-ingredient.
Class
Synthetic 16-amino-acid growth-hormone fragment (Tyr-stabilized hGH 176-191 / 177-191 analog)
Half-life
~30-60 minutes
Routes
Subcutaneous, Oral
Category
Weight Loss & Metabolic
Researched benefits
What it's studied for
Selective lipolysis without IGF-1 elevation
AOD-9604 was designed to stimulate fat breakdown and inhibit fat storage while leaving IGF-1 unchanged. Phase 1 and Phase 2 human trials confirmed this selectivity cleanly, distinguishing it from full-length GH and GH secretagogues that raise IGF-1.
Fat mobilization in preclinical models
In obese (ob/ob) mouse studies, AOD-9604 stimulated lipolysis and reduced body fat, proposed to work via increased beta-3 adrenergic receptor expression in adipose tissue (Heffernan et al., 2001, PMID 11713213).
No glucose or insulin disruption
Across the human program AOD-9604 did not impair fasting glucose or insulin sensitivity, avoiding the glucose intolerance associated with growth hormone. This underlies its benign safety profile but also reflects limited physiological potency.
Favorable, well-tolerated safety profile
The published human trials reported clean tolerability with only mild adverse events over 24 weeks at doses up to 30 mg daily, supporting its GRAS ingredient-safety positioning.
Proposed joint and cartilage applications
After the obesity program ended, Metabolic Pharmaceuticals explored AOD-9604 for osteoarthritis, citing unpublished chondroprotective data. Published human evidence for joint or cartilage benefit remains limited and does not support strong marketing claims.
Mechanism
How it works
AOD-9604 is built on the "lipolytic fragment" hypothesis proposed by Frank Ng and colleagues at the Howard Florey Institute in the 1990s: that full-length human growth hormone contains functionally distinct domains, with an N-terminal region responsible for growth-promoting effects (IGF-1 elevation, cartilage and organ growth) and a C-terminal region (residues 177-191) responsible for the fat-metabolizing effects. AOD-9604 is a synthetic version of that C-terminal domain with an added N-terminal tyrosine for stability and receptor binding, engineered to keep the lipolytic signal while discarding the anabolic and diabetogenic effects.
Mechanistically, the peptide is proposed to stimulate lipolysis (fat breakdown) and inhibit lipogenesis (fat storage) in adipocytes without engaging the growth hormone receptor in a way that triggers hepatic IGF-1 production. Preclinical studies in obese mice suggested it acts partly by increasing beta-3 adrenergic receptor (beta-3 AR) expression in adipose tissue, a receptor that mediates fat oxidation and thermogenesis in rodents. Critically, no IGF-1 elevation or hyperglycemia was observed, which was consistent across studies and is the compound's defining pharmacological feature.
The likely reason the mechanism did not translate to humans is that beta-3 AR expression in human adipose tissue is far lower than in rodents. The pivotal Phase 2B trial (n=536, 24 weeks, 1 mg and 30 mg subcutaneous daily versus placebo) produced no statistically significant weight loss at any dose; weight loss across all groups was roughly 2-3 kg, indistinguishable from placebo. The compound did what it was designed to do pharmacologically, but the magnitude of the lipolytic effect was too small to matter clinically for obesity.
Pharmacokinetically, AOD-9604 has a short half-life of about 30-60 minutes and lipolytic effects that are acute and dose-dependent. Oral bioavailability is expected to be negligible to very low: as a 16-amino-acid peptide it is degraded by gastric acid and intestinal proteases, so oral supplement forms are mechanistically unlikely to deliver meaningful active peptide to the circulation unless a specialized protective formulation is used, which commercial products generally are not.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Reconstitute lyophilized powder with bacteriostatic water (not plain sterile water, since the benzyl-alcohol preservative matters for multi-use vials). A common approach is 2 mL BAC water into a 2 mg vial or 5 mL into a 5 mg vial, both yielding 1 mg/mL (1000 mcg/mL): at that concentration a 250 mcg dose is 0.25 mL (25 units on a U-100 insulin syringe), 300 mcg is 0.30 mL (30 units), and 500 mcg is 0.50 mL (50 units). Inject the water slowly down the side of the vial rather than onto the powder, swirl gently (do not shake), and store reconstituted solution refrigerated (2-8C), protected from light, using within 3-4 weeks. Discard if cloudy, discolored, or containing particulates.
Beginner
- Dose
- 250-300 mcg
- Frequency
- Once daily
- Timing
- Morning, fasted (30+ minutes before food)
- Duration
- 12-week trial minimum
- Route
- Subcutaneous (abdomen or thigh, pinch-and-inject)
Community monotherapy protocol used to assess individual response. Rotate injection sites to prevent lipoatrophy. Note that AOD-9604 failed its pivotal obesity trial, so any observed change likely reflects concurrent diet and training.
Intermediate
- Dose
- 300-500 mcg
- Frequency
- Once daily
- Timing
- Morning, fasted
- Duration
- 12-16 week cycles
- Route
- Subcutaneous
Typically run inside a stack (e.g. with Ipamorelin/CJC-1295, Tesamorelin, MOTS-c, or a GLP-1 agonist). Real efficacy in these combinations comes from the other components; AOD-9604's contribution is speculative.
Advanced
- Dose
- 500 mcg (up to 1 mg)
- Frequency
- Once daily
- Timing
- Morning, fasted
- Duration
- 12+ weeks with pre-specified stop criteria
- Route
- Subcutaneous
Higher-end community/body-recomposition dose; 1 mg is rarely used and not clearly more effective. The Phase 2B trial used 1 mg and 30 mg daily and still failed on efficacy. Use with objective baseline metrics (DEXA, labs, photos) and a defined discontinuation point.
Oral (supplement form)
- Dose
- 500 mcg to 5 mg
- Frequency
- Once daily
- Timing
- Per product label
- Duration
- Per product
- Route
- Oral
Sold under the US GRAS framework. Systemic absorption is minimal because the peptide is degraded by gastric proteases; expected physiological effect is limited.
- AOD-9604 is not weight-based; standard flat doses are used.
- No cycling requirement is established and no taper is needed on discontinuation (no withdrawal syndrome or receptor downregulation concern).
- There is no FDA-approved or clinically validated human dosing protocol; all injectable regimens are community-derived from research-peptide use.
- Store lyophilized (unreconstituted) vials refrigerated at 2-8C, protected from light; stable for 2+ years. Do not freeze reconstituted solution.
- Because AOD-9604 and the closely related HGH Fragment 176-191 elute similarly on HPLC, an HPLC-only certificate of analysis cannot confirm which molecule is in a vial; mass-spectrometry identity confirmation is the meaningful check.
- Research-grade product quality varies, so a labeled 500 mcg dose may deliver less actual active peptide; verify a recent third-party COA (identity by mass spec, purity by HPLC >95%, endotoxin <1 EU/mg).
Evidence
Research & clinical studies (3)
The effect of the growth hormone fragment AOD9604 on adipose tissue
In obese mouse models AOD9604 stimulated lipolysis and reduced fat mass via beta-3 adrenergic receptor activation without affecting IGF-1 levels or blood glucose, suggesting a targeted fat-reducing mechanism.
PMID 11713213Metabolic Pharmaceuticals Phase 2B obesity trial of AOD-9604 (Heffernan et al.)
In 536 obese adults given 1 mg or 30 mg subcutaneously daily for 24 weeks versus placebo, no dose produced statistically significant weight loss over placebo, leading Metabolic Pharmaceuticals to abandon the obesity program.
Preclinical characterization of C-terminal hGH lipolytic fragments (Ng et al.)
C-terminal fragments of human growth hormone retained the fat-metabolism-improving effects of full-length hGH in rodent models without causing IGF-1 elevation, glucose intolerance, or cartilage/organ growth, providing the rationale for AOD-9604.
Combinations
Stacking & blends
AOD-9604 + Tirzepatide: Advanced Body Composition
Fat loss and body recomposition
Pairs AOD-9604's direct adipocyte lipolysis with tirzepatide's dual GIP/GLP-1 appetite and energy-balance regulation for complementary peripheral and central mechanisms. Tirzepatide drives essentially all of the weight loss; the AOD-9604 contribution is marginal and unproven.
GH Axis Optimization
Body composition support and GH pulses
Ipamorelin (ghrelin mimetic) and short-acting CJC-1295 produce synergistic pulsatile GH release for recovery, sleep, and modest fat loss. AOD-9604 adds no proven independent contribution but little added cost or risk.
Comprehensive Fat Loss Stack
Visceral fat reduction
Tesamorelin (FDA-approved GHRH analog with Phase 3 visceral-fat evidence) is the efficacy driver, MOTS-c contributes emerging mitochondrial metabolic effects, and AOD-9604 is the weakest mechanistic link.
Recovery and Body Composition
Injury recovery and tissue healing
BPC-157 and TB-500 target soft-tissue repair; AOD-9604 is included peripheral to recovery goals rather than as the primary agent.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Pregnancy
- Breastfeeding / active lactation
- Pediatric patients under 18
- Known hypersensitivity to AOD-9604 or peptide excipients
- Active malignancy (use with caution as theoretical precaution)
- Active eating disorder or significant body-image vulnerability
AOD-9604 has a notably benign side-effect profile: clinical trials reported minimal adverse events, no IGF-1 elevation, and no glucose intolerance over 24 weeks at doses up to 30 mg daily. However, the benign profile partly reflects limited physiological activity. No clinically significant drug interactions are documented; theoretical cautions include additive injection-site bruising with anticoagulants and elevated injection-site infection risk with immunosuppressants. Long-term safety data is absent because Phase 3 was never completed, and research-grade product carries standard purity and contamination risks.
FAQ
AOD-9604 — common questions
Does AOD-9604 actually work for fat loss?
Based on peer-reviewed clinical evidence, no. It did not produce statistically significant weight loss versus placebo in its pivotal Phase 2B trial of 536 obese adults over 24 weeks at doses up to 30 mg daily. Preclinical rodent data showed lipolytic activity, but the human effect size was too small to be clinically meaningful, and the program was discontinued around 2007.
How is AOD-9604 different from growth hormone?
AOD-9604 is a 16-amino-acid fragment of hGH (residues 177-191 plus an added tyrosine), while full-length hGH is a 191-amino-acid protein. It was designed to retain GH's fat-metabolism effects without the growth-promoting effects, and it does not raise IGF-1. The tradeoff is that it also lacks most of hGH's fat-loss potency.
Is AOD-9604 FDA approved?
Not as a drug for any indication. In the US it holds a 2014 GRAS food-ingredient determination, which certifies safety as a supplement ingredient but not efficacy for weight loss. Marketers sometimes misrepresent GRAS status as 'FDA-cleared,' which is inaccurate.
Can AOD-9604 be taken orally?
It is marketed in oral supplement form under GRAS, but as a 16-amino-acid peptide its oral bioavailability is expected to be essentially zero because it is degraded by gastric acid and digestive proteases before absorption. Most commercial oral products lack the specialized protective formulation that would be needed, so systemic effect is likely negligible.
Is it the same as HGH Fragment 176-191?
No. They are closely related and target the same GH region, but are catalogued as distinct molecules with different CAS numbers (AOD-9604 is 221231-10-3; the fragment is 66004-57-7) and slightly different masses. AOD-9604 is the tyrosine-modified form that actually advanced into human trials. Because they elute similarly on HPLC, mass spectrometry is needed to confirm identity.
Does AOD-9604 help with joint pain or cartilage repair?
Metabolic Pharmaceuticals explored repositioning it for osteoarthritis after the obesity failure, citing unpublished chondroprotective data, but published human evidence for joint or cartilage benefit is limited and does not support strong marketing claims.
Can I combine AOD-9604 with a GLP-1 agonist like semaglutide?
There are no known drug interactions and the mechanisms don't overlap, so it can be combined. But if you are on a GLP-1 agonist producing 15-20% weight loss, essentially all the effect comes from the GLP-1; adding AOD-9604 adds cost and injection burden without proven benefit. Many practitioners would recommend dropping it.
How do I know my AOD-9604 is legitimate?
Look for a vendor-independent third-party certificate of analysis showing peptide identity by mass spectrometry, purity by HPLC (>=95%), and endotoxin testing (<1 EU/mg). For AOD-9604 specifically, mass-spec identity confirmation matters because an HPLC-only COA cannot distinguish it from the cheaper HGH Fragment 176-191.
