Metabolic & Weight LossWell-Tolerated

AOD-9604

Also known as: Anti-Obesity Drug 9604, hGH Fragment 176-191, Tyr-hGH177-191

A modified fragment of human growth hormone (hGH 176-191) that promotes fat loss without the negative effects on blood sugar or cell proliferation associated with full HGH.

Half-Life

Short (30-60 minutes)

Typical Dose

250-500 mcg

Frequency

Once daily

Routes

Subcutaneous

Overview

AOD-9604 (Anti-Obesity Drug 9604) is a synthetic peptide fragment corresponding to the C-terminal region of human Growth Hormone (specifically amino acids 176-191), with an added tyrosine at the N-terminus. It was developed by Metabolic Pharmaceuticals in Australia specifically for fat loss.

The key innovation of AOD-9604 is that it retains the fat-burning properties of growth hormone while eliminating the negative effects on blood sugar and IGF-1 that limit HGH use for weight management.

Key Characteristics

  • Origin: Modified fragment of human growth hormone
  • Classification: Lipolytic peptide
  • Structure: hGH amino acids 176-191 + Tyrosine
  • FDA Status: Not approved; GRAS status for food (2016)
  • Unique Feature: Fat loss without HGH side effects

Why a Fragment?

Full-length growth hormone has multiple effects:

  • Fat loss (via C-terminal region) ✓
  • Muscle growth (via IGF-1 increase) ✓
  • Insulin resistance (problematic) ✗
  • Cell proliferation (cancer concern) ✗

AOD-9604 isolates the fat-burning portion while avoiding the problematic effects.

Mechanism

Primary Mechanisms

1. Lipolysis Stimulation

Fat breakdown pathway:

  • Stimulates beta-3 adrenergic receptors
  • Activates hormone-sensitive lipase
  • Increases triglyceride breakdown
  • Releases free fatty acids
  • Promotes fat oxidation

2. Lipogenesis Inhibition

Blocks fat creation:

  • Inhibits lipogenic enzymes
  • Reduces new fat cell formation
  • Prevents triglyceride synthesis
  • Decreases fat storage

3. No IGF-1 Increase

Critical safety feature:

  • Does NOT increase IGF-1 levels
  • No growth factor proliferation effects
  • No muscle building (but no cancer risk)
  • No glucose metabolism disruption

4. No Blood Sugar Effects

Unlike full HGH:

  • No insulin resistance
  • No glucose increase
  • Safe for diabetics (potentially)
  • No metabolic side effects

How It Differs from HGH

| Effect | Full HGH | AOD-9604 | |--------|----------|----------| | Fat Loss | Yes | Yes | | Muscle Growth | Yes | No | | IGF-1 Increase | Yes | No | | Insulin Resistance | Yes | No | | Cell Proliferation | Yes | No | | Cost | Very High | Lower |

Research

Research Note: AOD-9604 completed Phase 2 clinical trials for obesity but was not pursued to approval. It later received GRAS (Generally Recognized as Safe) status from FDA for food use.

Clinical Trials (Historical)

Phase 2 Studies

Metabolic Pharmaceuticals trials showed:

  • Statistically significant weight loss vs placebo
  • No significant adverse events
  • No change in glucose tolerance
  • No IGF-1 elevation
  • Good tolerability

Why Not Approved?

Despite positive results:

  • Weight loss modest compared to newer drugs
  • Competition from other approaches
  • High cost of Phase 3 development
  • Company shifted focus to GRAS pathway

Mechanism Studies

Lipolysis Research

Laboratory studies confirm:

  • Direct lipolytic activity in adipocytes
  • Inhibition of lipogenesis
  • Activity independent of GH receptor
  • Selective action on fat cells

Cartilage Repair (Emerging)

2025 Research

Recent interest in:

  • Cartilage regeneration potential
  • Osteoarthritis treatment studies
  • Joint health applications
  • Injectable and oral formulations

GRAS Status (2016)

FDA determined AOD-9604 is:

  • Generally Recognized as Safe
  • Approved for use in food products
  • Demonstrates excellent safety profile
  • Opens door for oral formulations

Dosing

Disclaimer: AOD-9604 is not FDA-approved for weight loss. GRAS status applies to food use only. All dosing information is for research reference only.

Research Protocols

ProtocolDoseFrequencyDuration
Fat Loss (Injectable)250-500 mcgOnce daily12-24 weeks
Standard Protocol300 mcgOnce daily (morning, fasted)12 weeks
Oral (Research)500-1000 mcgOnce dailyVaries
Split Dose150-250 mcg2x daily12 weeks

Administration Notes

Timing

  • Best taken in the morning
  • On empty stomach (fasted state)
  • Wait 30-60 minutes before eating
  • Fat in stomach may reduce absorption

Injection Site

  • Subcutaneous (belly fat)
  • Rotate injection sites
  • Near target fat area (theoretical local effect)
  • Can inject into stubborn fat deposits

Duration

  • Results typically seen after 4-8 weeks
  • Full effects may take 12+ weeks
  • Can be used long-term (safety profile)
  • Cycling may maintain sensitivity

Reconstitution

  • Use bacteriostatic water
  • Typical: 5mg vial + 2.5ml water = 2mg/ml
  • Store refrigerated
  • Use within 4-6 weeks
  • Stable peptide

Pharmacokinetics

Absorption

  • Subcutaneous: Rapid absorption
  • Oral: Variable bioavailability (GRAS formulations improving this)

Distribution

  • Limited systemic distribution
  • Concentrates at injection site
  • Short activity window

Metabolism

  • Rapid peptide breakdown
  • No active metabolites
  • Natural amino acid degradation

Elimination

  • Half-life: 30-60 minutes (estimated)
  • Rapid clearance
  • No accumulation
  • Daily dosing required

Synergy & Stacking

Common Combinations

AOD-9604 + CJC-1295/Ipamorelin

For comprehensive approach:

  • AOD-9604: Fat loss
  • CJC-1295/Ipamorelin: GH benefits including muscle
  • Complementary mechanisms
  • Popular in wellness settings

AOD-9604 + L-Carnitine

Fat burning stack:

  • AOD-9604: Liberates fatty acids
  • L-Carnitine: Transports fatty acids into mitochondria
  • Enhanced fat oxidation

AOD-9604 + Fasting Protocol

Synergistic with intermittent fasting:

  • Both promote fat mobilization
  • Morning fasted administration
  • Extended fat-burning window

Safety

Known Side Effects

Common (generally mild)

  • Injection site reactions
  • Mild headache
  • Flushing (rare)

Notably ABSENT:

  • No glucose/insulin changes
  • No IGF-1 elevation
  • No water retention
  • No carpel tunnel (unlike HGH)
  • No cell proliferation concerns

Contraindications

Use with caution if:

  • Active cancer (any growth-affecting compound)
  • Pregnancy or breastfeeding
  • History of hypersensitivity to peptides

Generally considered safe for:

  • Diabetics (no glucose effect)
  • Cardiovascular disease patients
  • Most adults seeking fat loss

Safety Advantage: AOD-9604's excellent safety profile led to its GRAS designation. It lacks the problematic effects of full HGH while retaining fat-burning benefits.

Drug Interactions

  • No significant drug interactions identified
  • May theoretically complement diabetes medications
  • No CYP450 interactions

Monitoring

Before Starting

  • Body composition baseline (DEXA ideal)
  • Weight and measurements
  • Photographs
  • Fasting glucose (baseline documentation)

During Use

  • Weight trends
  • Body composition changes
  • Waist circumference
  • Progress photographs

No Required Labs

  • No IGF-1 monitoring needed
  • No glucose monitoring required (unlike HGH)
  • General wellness labs as desired

Regulatory

Current Status

| Region | Status | |--------|--------| | United States | GRAS for food (2016); not FDA-approved as drug | | WADA | Prohibited (S2 category) | | Australia | Originally developed there; research chemical | | TGA | Not approved for therapeutic use |

Legal Considerations

  • GRAS status = recognized as safe
  • Not approved as weight loss drug
  • Available as research chemical
  • Athletes: Strictly banned
  • Oral formulations in some nutraceuticals

Clinical Outlook

AOD-9604 occupies a unique space:

  • Proven mechanism of action
  • Excellent safety profile (GRAS)
  • Never completed drug approval
  • Growing interest in cartilage applications
  • Oral formulations expanding accessibility

References

[1] Ng FM, et al.. Metabolic effects of a synthetic peptide analogue of growth hormone 177-191. Hormone and Metabolic Research (2000)
[2] Heffernan M, et al.. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and rats. Endocrinology (2001)
[3] FDA. GRAS Notice 000617: AOD-9604. FDA GRAS Notices (2016)
[4] Obesity Peptide Research. Growth Hormone Fragments in Metabolic Disease. Obesity Research Reviews (2025)