AOD 9604 for Weight Loss: Not Recommended
AOD 9604 should not be used for weight loss in adults with obesity or metabolic disorders, as it lacks FDA approval, has no supporting evidence from completed clinical trials, and is not mentioned in any current obesity treatment guidelines.
Current Status of AOD 9604
AOD 9604 is a synthetic peptide fragment derived from the C-terminus of human growth hormone that was investigated in the early 2000s for potential anti-obesity effects 1, 2. The compound was in phase IIa clinical trials by 2002 but never progressed beyond early development 3. No phase III trials were ever completed, and the drug was never approved by the FDA or any regulatory agency for obesity treatment 1, 2.
The mechanism proposed involved increasing adipose tissue breakdown and potentially modulating beta-3 adrenergic receptor expression in preclinical mouse models 4. However, these animal studies from 2001 have not translated into human clinical efficacy data 4.
Evidence-Based Alternatives
The 2022 AGA Clinical Practice Guidelines comprehensively reviewed all FDA-approved anti-obesity medications and AOD 9604 is conspicuously absent from these recommendations 5. Instead, the following evidence-based options are available:
First-Line Pharmacotherapy Options
Semaglutide 2.4 mg subcutaneous weekly achieves mean weight loss of 14.9% at 68 weeks with 64.9% of patients achieving ≥10% total body weight loss, representing the most effective currently available pharmacotherapy 5
Tirzepatide (GIP/GLP-1 co-agonist) produces mean weight loss of 21% at 72 weeks, with nearly 40% of patients achieving ≥25% total body weight loss at the highest dose 5
Liraglutide 3.0 mg produces 5.4% weight loss at 56 weeks and has FDA approval specifically for obesity management 5, 6
Phentermine-topiramate ER achieves 9.8-10.9% weight loss at one year with the 15/92 mg dose 5, 6
Conditional Recommendations
Naltrexone-bupropion ER produces 4.8-6% weight loss at 56 weeks and may be preferred in patients with comorbid depression or those seeking smoking cessation 5, 6
Phentermine monotherapy is FDA-approved for short-term use (12 weeks) but often used off-label for longer duration, though it should be avoided in patients with cardiovascular disease 5
Critical Safety Considerations
Using unapproved compounds like AOD 9604 poses several risks:
- No established safety profile in humans from adequate clinical trials
- Unknown drug interactions with medications for metabolic disorders
- Lack of quality control in commercially available preparations
- No regulatory oversight for manufacturing or distribution
- Potential legal and liability issues for prescribers
Recommended Clinical Approach
For adults with obesity (BMI ≥30) or overweight (BMI ≥25) with weight-related complications 5:
Initiate comprehensive lifestyle interventions including multicomponent behavioral interventions (ideally ≥14 sessions in 6 months), reduced-calorie diet (500 kcal daily deficit), and 150 minutes of physical activity per week 5
Add FDA-approved pharmacotherapy when lifestyle modifications alone are insufficient, prioritizing GLP-1 receptor agonists (semaglutide 2.4 mg or liraglutide 3.0 mg) or tirzepatide given their superior efficacy and cardiovascular benefits 5
Monitor response at 12 weeks and discontinue medication if <5% weight loss is achieved 6
Consider bariatric surgery for patients with BMI ≥30 with approved indications, as it achieves 25-30% weight loss at 12 months 5
Common Pitfall to Avoid
Do not prescribe or recommend investigational or unapproved compounds like AOD 9604, even if marketed as "peptide therapy" or available through compounding pharmacies. The 2022 AGA guidelines explicitly state that only FDA-approved medications with demonstrated efficacy and safety in phase III trials should be used 5. Stick to evidence-based therapies with established benefit-risk profiles and regulatory approval.