What Is AOD 9604 Peptide?

AOD 9604, also known as the anti-obesity drug fragment 9604, is a synthetic peptide derived from the C-terminal region (amino acids 177–191) of human growth hormone (hGH).

Structurally, AOD 9604 mimics the portion of hGH responsible for stimulating lipolysis (fat breakdown) and inhibiting lipogenesis (fat formation), without significantly influencing insulin-like growth factor 1 (IGF-1) production or systemic growth processes [1].

This selectivity distinguishes it from full-length hGH, making it an attractive candidate for metabolic regulation and body composition improvement [2].

Potential applications of AOD9604 have expanded beyond weight management to include joint recovery, cartilage regeneration, and metabolic health. However, regulatory approval remains limited to cosmetic or research use in most regions.

In six clinical trials and all preclinical studies, AOD 9604 demonstrated safety and tolerability [3]. It continues to be elucidated for its targeted metabolic effects, representing a promising next-generation approach to addressing obesity and related metabolic dysfunction.

What Does AOD 9604 Peptide Do?

AOD9604 targets fat loss while supporting joint and cardiometabolic health. Research also highlights its safety and efficacy.

HGH Mimetic and Fat Loss

Most research regarding AOD 9604 has focused on fat loss, which is the peptide’s most obvious effect. Unlike other weight loss agents, it works directly on fat cells instead of regulating appetite.

Clinical trials found that AOD 9604 has no effect on serum IGF-1 levels, suggesting that it doesn’t act via IGF-1. Also, AOD 9604 has no adverse effect on carbohydrate metabolism or any immunogenic properties. After cessation of use, no withdrawal, rebound weight gain, or any other serious adverse event occurred [4].

A preclinical study conducted on obese (ob/ob) and lean C57BL/6J mice assessed the long-term metabolic effects of AOD 9604 compared with full-length hGH [5].

Results showed that:

Both hGH and AOD 9604 significantly reduced body weight by 10–15% in 14 days in obese mice compared to the control group (p < 0.05).
Treatment with either peptide increased fat oxidation and plasma glycerol levels by >30%, suggesting enhanced lipolytic activity.
AOD 9604 did not cause hyperglycemia or suppress insulin secretion (p > 0.05). However, hGH significantly elevated glucose and reduced insulin levels (p < 0.05).
AOD 9604 did not compete for the hGH receptor and did not induce cell proliferation, distinguishing AOD 9604 mechanistically from hGH.

AOD 9604 replicates the fat-reducing and lipolytic effects of hGH without affecting glucose metabolism or stimulating cellular proliferation, acting independently of the hGH receptor.

Based on these results, AOD 9604 could represent a safer and more effective alternative for long-term obesity management.

Joint Health

Another interesting application of AOD 9604 is its potential use in regenerating damaged tissues caused by degenerative inflammatory conditions.

A rabbit study used a collagenase-induced knee osteoarthritis (OA) model to assess the regenerative effects of AOD 9604, either alone or in combination with hyaluronic acid (HA) [6].

A total of 32 mature New Zealand white rabbits received two intra-articular injections of 2 mg collagenase type II to induce cartilage degeneration in each knee joint.

Rabbits were then divided into four groups for weekly injections:

Group 1: 0.6 mL saline (control)
Group 2: 6 mg hyaluronic acid (HA)
Group 3: 0.25 mg AOD 9604
Group 4: 0.25 mg AOD 9604 + 6 mg HA

Results showed that:

Group 4 had the lowest degeneration scores, outperforming both AOD9604 alone and HA alone (p < 0.05).
In terms of functional recovery, lameness duration was significantly shorter in Group 4 compared to Groups 1, 2, and 3 (p < 0.05).
The combination of AOD9604 and HA demonstrated additive or synergistic effects on both structural and functional outcomes.

These findings support further investigation of AOD 9604 as a regenerative adjunct in osteoarthritis therapy, potentially offering an approach for cartilage protection and symptom relief.

Cardiometabolic Health

When comparing AOD 9604 to its parent hormone (hGH), it is important to understand the similarities and differences in the systemic effects on the body.

A preclinical metabolic study evaluated the oral safety and efficacy of AOD 9604 in obese Zucker rats, a model for metabolic syndrome and insulin resistance [7].

The rats received 19 consecutive days of AOD 9604 orally at 500 µg/kg body weight, or a vehicle control.

AOD9604 treatment resulted in:

>50% reduction in body weight gain compared with controls (15.8 ± 0.6 g vs. 35.6 ± 0.8 g, p < 0.001).
Significant increases in lipolytic enzyme activity in adipose tissue, suggesting enhanced breakdown of triglycerides into free fatty acids.
No impairment of insulin sensitivity, and normal glucose usage.

These findings support the potential development of AOD9604 as an orally-active, metabolically safe therapeutic agent for treating obesity.

Although AOD 9604 has shown promise in a few preclinical domains, it remains an investigative peptide.

Safety and Efficacy

A review paper examined six randomized clinical trials to assess the safety, tolerability, and metabolic impact of AOD 9604. There were around 900 participants in total, most of whom were obese but otherwise healthy. AOD 9604 was given either intravenously (25–400 μg/kg body weight) or orally (0.25–54 mg/day) [4].

Results showed that:

Acute IV and Oral Studies

- - No significant changes in blood glucose, glycerol, or IGF-1 levels.
  - AOD 9604 was well tolerated up to 400 μg/kg IV or 54 mg orally.

Multiple-Dose and Long-Term Trials

- AOD 9604 showed no effect on serum IGF-1 (mean change <1.3 nmol/L, p > 0.5) and no impairment in glucose tolerance, as oral glucose tolerance test results were stable across all groups).
- No anti-AOD 9604 antibodies were detected in any participants.

The incidence of significant adverse events (3.6%) was similar to placebo and unrelated to treatment (skin lesions, infections, or musculoskeletal pain).
Even at high doses, no pro-diabetic or growth-promoting effects were observed, confirming the lack of hGH receptor activation.

The peptide demonstrated neutral effects on carbohydrate metabolism and potential improvement in glucose tolerance in participants with prediabetic markers.

AOD 9604 demonstrated an excellent safety and tolerability profile in nearly 900 human subjects, supporting its potential as a non-hormonal, fat-modulating peptide for long-term use in the treatment of obesity and metabolic optimization.