AOD-9604 side effects

Where the data come from

All human safety data for AOD-9604 come from six randomized, placebo-controlled trials that its developer, Metabolic Pharmaceuticals, funded between 2001 and 2006, in 893 adults given the peptide by mouth or by vein.¹ The safety summary was written by employees or consultants of the developer.² The lists below follow that record, then the gaps and warnings FDA described in its 2024 review.

Common side effects (seen with AOD-9604 and placebo alike)

• Headache: the most common adverse event across the trials.¹ Counting all groups, including placebo, it affected 42.6% of participants during the 12-week trial and 25.9% during the 24-week trial.¹
• Gut symptoms: diarrhea, flatulence, nausea and increased appetite were common in the oral trials.¹ Diarrhea affected 9.0% of all participants in the 12-week trial and 7.8% in the 24-week trial.¹
• Colds and back pain: in the 24-week trial, nasopharyngitis affected 17.1% of participants and back pain 8.2%, across all groups.¹
• First IV study: 12 of 15 healthy men reported 29 events across all treatments, including headache, fatigue, low blood sugar, dizziness, nasopharyngitis and cough, plus single reports of injection-site bruising, injection-site pain and an application-site reaction.¹ The events were spread evenly between AOD-9604 and placebo.¹
• Overall rate: in the 24-week trial, 83.2% of the placebo group and 75.6% of the 0.25 mg group had at least one adverse event.¹

Less common, judged possibly related

• Euphoria: 5 of 23 obese men reported mild or moderate euphoria during IV AOD-9604 periods, and none during placebo.¹
• Chest tightness: one severe feeling of chest tightness after a 50 microgram per kg IV dose.¹
• Serious diarrhea: one case at the 54 mg oral dose in the single-dose study, even though the paper's abstract states that no related serious adverse event occurred.¹

Serious adverse events

• Tumors in the 12-week trial: five serious events, all in AOD-9604 groups: basal cell carcinoma, squamous cell carcinoma and a lipoma in the 20 mg group, breast cancer in the 5 mg group and melanoma in the 10 mg group.¹ The investigator judged none related; FDA says there is not enough information to show they were unrelated.¹²
• 24-week trial: 18 of 502 people (3.6%) had at least one serious adverse event, spread similarly across groups: 8 on placebo, 3 on 0.25 mg, 1 on 0.5 mg and 6 on 1 mg.¹
• FDA reporting system: FDA's adverse event database returned no AOD-9604 reports in a search through January 7, 2024, and FDA notes that a lack of reports does not mean a substance is safe.²

Gaps in the evidence

• Injection under the skin: FDA found no human data for subcutaneous use, although most clinics offering AOD-9604 sell injections or oral products.²
• Long-term use: the longest human exposure was 24 weeks of oral tablets.¹ FDA says there is not enough information to support long-term safety, and it identified no human study of how the body absorbs or clears the peptide.²
• Pregnancy: FDA identified no developmental or reproductive toxicity studies,² and the 12-week trial enrolled only women who could not become pregnant.¹
• Cancer risk in animals: FDA identified no carcinogenicity studies.²

Warnings

• Immune reactions: FDA is concerned about immunogenicity, because AOD-9604 can form aggregates and carry peptide-related impurities.² FDA's safety-risks page says compounded AOD-9604 may pose a significant immunogenicity risk for certain routes of administration.³
• Serious events of unclear cause: the same page says FDA has identified serious adverse events that may be associated with AOD-9604, though causality is not clear.³
• Product quality: FDA found that the certificates of analysis submitted to it, and public sources, lacked specific tests for impurities, aggregates and microbes, and that endotoxin testing for injectable use was lacking; it considers AOD-9604 not well characterized.²
• Animal toxicology: developer-linked authors reported no genotoxic or toxicological concerns after oral dosing for 6 months in rats and 9 months in monkeys.⁴ FDA's review of those studies found signals suggesting harm to bone health in rats, possible liver toxicity signals in monkeys and equivocal mutagenic signals in genotoxicity tests.²
• Athletes: WADA prohibits AOD-9604 at all times,⁵ and anti-doping scientists have validated a urine test that detects it down to 50 pg/mL.⁶

Related pages

Back to the AOD-9604 profile. The doses behind these events are in AOD-9604 dosage, reported outcomes are in AOD-9604 benefits and uses, and lab handling is in How to reconstitute AOD-9604. General background: Peptide safety basics.