AOD-9604 for Fat Loss: Does the Research Actually Support It?

What Is AOD-9604?

AOD-9604 (Advanced Obesity Drug 9604) is a synthetic peptide corresponding to the C-terminal fragment of human growth hormone, specifically amino acids 177-191 with a tyrosine modification at position 177. It was developed by Metabolic Pharmaceuticals in Australia with the goal of isolating the fat-burning properties of growth hormone without the anabolic or diabetogenic effects.^[1]

The premise is appealing: take the part of growth hormone responsible for lipolysis, remove the parts that cause side effects, and create a targeted fat-loss compound. But does the published research actually support this claim? This article examines the evidence critically.

How AOD-9604 Is Proposed to Work

Growth hormone stimulates lipolysis (fat breakdown) through a region in its C-terminal domain. AOD-9604 is designed to mimic this lipolytic signaling without activating the growth-promoting or glucose-elevating pathways mediated by the full GH molecule.

The proposed mechanism involves:

• Stimulating lipolysis: Increasing the release of stored fatty acids from adipocytes (fat cells) for use as energy
• Inhibiting lipogenesis: Reducing the conversion of non-fat calories into new stored fat
• No IGF-1 elevation: Unlike full growth hormone, AOD-9604 does not increase IGF-1 levels, avoiding the growth-promoting side effects
• No glucose effects: Does not impair glucose tolerance or insulin sensitivity, unlike full GH

This mechanism profile sounds ideal for targeted fat loss. The critical question is whether the evidence supports these claims at clinically meaningful doses in humans.

The Animal Data: Promising but Limited

The initial evidence for AOD-9604 came primarily from animal studies conducted in the late 1990s and early 2000s:

• In obese Zucker rats, AOD-9604 reduced body fat gain without affecting IGF-1 levels or insulin sensitivity^[1]
• In obese mice, the peptide reduced body weight by 50% more than placebo over 19 days
• Fat-specific effects were confirmed: lean mass was unaffected while adipose tissue decreased

These animal results were genuine and well-documented. The problem is that animal models of obesity, particularly genetically obese rodent strains, are notoriously poor predictors of human efficacy. Many compounds that work in ob/ob mice or Zucker rats fail to produce clinically meaningful effects in human clinical trials.

Human Clinical Trial Data: The Inconvenient Truth

This is where AOD-9604's story becomes complicated. Metabolic Pharmaceuticals conducted a phase 2b clinical trial in approximately 300 obese patients. The results were not what the company hoped for:

• Primary endpoint not met: AOD-9604 did not produce statistically significant weight loss compared to placebo in the phase 2b trial
• Effect size: The weight loss observed was modest and not clinically meaningful by FDA standards
• Development abandoned: Following the failed trial, Metabolic Pharmaceuticals discontinued development of AOD-9604 as a pharmaceutical obesity drug

The company subsequently licensed AOD-9604 for use in osteoarthritis treatment (injected into joints), pivoting away from the fat-loss indication entirely. This is an important detail that many promotional materials omit.

Putting AOD-9604 in Context

To understand where AOD-9604 stands in the fat-loss peptide landscape, compare it to compounds with stronger evidence:

Compound	Human Trial Weight Loss	FDA Status	Evidence Level
AOD-9604	Not significant (phase 2b failed)	Not approved	Animal data only
Semaglutide	14.9% (STEP 1)	FDA-approved	Multiple phase 3 trials
Tirzepatide	22.5% (SURMOUNT-1)	FDA-approved	Multiple phase 3 trials
Tesamorelin	Visceral fat reduction only	FDA-approved (lipodystrophy)	Phase 3 trials
MOTS-c	Limited human data	Not approved	Emerging preclinical

For a direct comparison, see our AOD-9604 vs Semaglutide analysis. The fat loss stack page covers protocols combining AOD-9604 with complementary compounds.

Why Is AOD-9604 Still Popular?

Despite the failed clinical trial, AOD-9604 remains one of the most commonly discussed fat-loss peptides. Several factors explain its continued popularity:

• Favorable safety profile: AOD-9604 has a genuinely clean safety record. It does not elevate IGF-1, does not impair glucose tolerance, and has minimal side effects. For people wary of GLP-1 side effects (severe nausea, pancreatitis risk), this is appealing.
• It was TGA-approved in Australia for osteoarthritis: This regulatory approval (for a different indication) lends perceived legitimacy.
• Availability: AOD-9604 was widely available through US compounding pharmacies until the FDA's 2024 Category 2 decision restricted compounding. It remains available through research peptide suppliers.
• Anecdotal reports: Individual user reports of fat loss are common in peptide communities, though these are subject to placebo effects, concurrent lifestyle changes, and reporting bias.

The Bottom Line

AOD-9604 has a solid mechanistic rationale, clean preclinical data, and a favorable safety profile. However, the compound failed its pivotal human clinical trial for fat loss, and pharmaceutical development for this indication was abandoned. The animal data does not translate to proven human efficacy.

This does not mean AOD-9604 is worthless — it means the evidence is weaker than what exists for FDA-approved alternatives. Anyone considering AOD-9604 should understand that they are choosing a compound with animal data over compounds with robust phase 3 human trial data.

For evidence-based fat loss options, explore our fat loss goal page and weight loss goal page, which cover compounds with the strongest clinical evidence.