Quick answer: the most common AOD-9604 side effects in human trials were headache and stomach or bowel upset such as diarrhea, gas and nausea.[1] After IV doses, a few people reported euphoria and one had severe chest tightness judged possibly related to the drug.[1] No human study has tested AOD-9604 injected under the skin, so its safety used that way is unknown.[2]
AOD-9604 is a fragment of human growth hormone that failed its weight-loss trials and is not approved anywhere. This page covers what the trials recorded, what FDA flagged in its 2024 review and what remains unknown. See also our AOD-9604 profile, AOD-9604 dosage, AOD-9604 results and the growth hormone peptides hub.
Where the safety data come from
Almost everything known about AOD-9604 side effects comes from six trials run by its developer in Australia between 2001 and 2006, involving 893 people.[1] The authors were employees or consultants of the company that funded the trials.[2] Two trials gave IV infusions; four used capsules or tablets by mouth.[1]
FDA reviewed this summary in 2024 and found it lacked detail: adverse events were often not broken down by dose or treatment, and lab values were not reported.[2]
AOD-9604 side effects reported in trials
| Study | Dose and route | What was reported |
|---|---|---|
| METAOD001 (15 men) | 25 to 400 mcg/kg IV | 29 mild events in 12 men; headache (6), fatigue (4), low blood sugar (3), dizziness (3); none severe |
| METAOD002 (23 men with obesity) | 25 to 100 mcg/kg IV | Headache in 16 of 23 (69.6%); euphoria in 5 of 23 only during AOD-9604 periods; 1 severe chest tightness possibly related |
| METAOD003 (17 men) | 9 to 54 mg by mouth, single doses | 97 events; headache, diarrhea, gas, increased appetite, nausea; 1 serious case of diarrhea possibly related (54 mg) |
| METAOD004 (36 men) | 9 to 54 mg by mouth for 7 days | More headaches, diarrhea and gas at 54 mg |
| METAOD005 (300 adults) | 1 to 30 mg by mouth for 12 weeks | During treatment, headache 42.6% and diarrhea 9.0% across all groups; similar in placebo and AOD-9604 groups |
| OPTIONS (502 adults) | 0.25 to 1 mg by mouth for 24 weeks | Nasopharyngitis 17.1%, headache 25.9%, back pain 8.2%, diarrhea 7.8% across all groups; similar to placebo |
Source: the company’s safety summary.[1]
Headache
Headache was the single most common complaint in nearly every study, from 6 reports in the first IV study to about 7 in 10 men in the second.[1] In the two long trials, headache was also common in the placebo run-in period (30.4% and 14.5% before active treatment), so not all of it can be blamed on the drug.[1]
Stomach and bowel effects
Diarrhea, gas, nausea and increased appetite were reported after oral doses, and became more frequent at the highest dose tested, 54 mg.[1] One case of diarrhea at 54 mg was classed as serious and possibly related.[1]
Chest tightness, palpitations and euphoria
In the IV study in men with obesity, mild to moderate euphoria was reported by 5 of 23 men, only while they were receiving AOD-9604, and one severe episode of chest tightness at 50 mcg per kg was judged possibly related.[1] The lead investigator of most of the trials later described headache, chest tightness, palpitations and euphoric feelings in short-term injection studies.[3]
Serious adverse events, including cancers
In the 12-week trial, five people on AOD-9604 had serious adverse events: basal cell carcinoma, squamous cell carcinoma and a lipoma (all at 20 mg), breast cancer (5 mg) and malignant melanoma (10 mg).[1] The investigator judged none related to the drug, noting none occurred at the highest dose.[1]
FDA disagreed that this settled the question. It wrote that it had concerns about these cancers and that the information was insufficient to tell whether they were unrelated.[2] FDA’s safety reviewers also said they could not identify a safety signal either way from data this limited.[2]
In the 24-week trial, 18 people (3.6%) had at least one serious adverse event, most often injuries, with a similar spread across groups.[1]
What did not change
The trials looked for the problems linked to full growth hormone. According to the company’s summary:[1]
- IGF-1 (a growth-related hormone) did not change significantly with AOD-9604.
- Blood sugar and glucose tolerance did not worsen, at doses up to 1 mg a day for 24 weeks.
- Antibodies against AOD-9604 were not found in the people tested, though only a subset was tested and only after oral use.
Animal and lab findings FDA flagged
FDA’s 2024 review found warning signs in the one published animal toxicology report:[2]
- Bone: in rats given AOD-9604 by mouth for 6 months, blood osteocalcin (a bone-turnover marker) shifted in a dose-related way, which FDA called a possible signal of harm to bone.
- Liver: female monkeys given the highest dose for 9 months all showed small fluid spaces (vacuolation) in liver cells, which can signal drug-related liver injury.
- Genetic damage: lab and rat tests gave mixed results, which FDA said cannot be dismissed as insignificant.
- Missing studies: no studies of effects on pregnancy, fertility or cancer risk were found.
Why injections raise extra concerns
AOD-9604 is a 16-amino-acid peptide held in shape by a disulfide bond. FDA notes that bond can break, letting the peptide clump into aggregates, and that injection under the skin is generally more likely than IV to provoke an immune response.[2] Possible immune effects range from harmless antibodies to severe reactions.[2]
FDA now lists AOD-9604 among bulk substances that may present significant safety risks, saying it lacks enough information to know whether the drug would cause harm.[4] Its compounding advisers voted 0 to 12 against allowing it.[5]
A search of FDA’s adverse event databases found no reports, but FDA stressed that this does not mean the substance is safe.[2]
For more on product quality, see compounded vs research-grade peptides.
What is still unknown
- Safety of injection under the skin or creams in people: never studied.[2]
- Long-term safety: the longest trial lasted 24 weeks, and FDA found insufficient information to support long-term use.[2]
- How the body absorbs and clears AOD-9604 in humans: no data.[2]
- Effects in pregnancy, in children or in people with serious illnesses: not studied.
Who should talk to a clinician first
Anyone considering AOD-9604 should discuss it with a licensed clinician, especially people who are pregnant or trying to conceive, have a history of cancer or melanoma, have liver or bone disease, or compete in tested sport. FDA’s review points to approved weight-loss medicines with established safety data.[2]
Questions to ask
- What approved options fit my goals, and what are their known side effects?
- I’ve used an unregulated peptide. Which symptoms should prompt me to seek care?
- Should we check anything, such as liver tests, if I have used it?
Related reading: AOD-9604 vs semaglutide, Fragment 176-191 vs AOD-9604 and peptides vs HGH.
This is general information, not medical advice.
