HGH Fragment 176-191 Harms

What side effects were reported in the trials?

Six randomized, double-blind, placebo-controlled trials enrolled 893 adults; in the first two, the substance was given intravenously, in the others orally. All of the trials were funded by the developer company; the authors of the summary have share or consulting ties with the company. ^[2]

• Single intravenous dose (15 healthy men): Across the AOD-9604 and placebo periods together, 12 people reported a total of 29 adverse events; the most common were headache (6 times) and fatigue, and unspecified hypoglycemia was recorded three times. There were no serious events. ^[2]
• Single intravenous dose (23 men with obesity): Mild to moderate headache was seen in 16 of 23 people. In one person, a severe “chest tightness sensation” was considered possibly related to the drug. In five people, mild to moderate euphoria was reported during AOD-9604 periods; there was no euphoria during the placebo period. ^[2]
• Single oral dose and 1-week studies (17 and 36 men with obesity): The most common were headache, diarrhea, gas, increased appetite and nausea. One case of diarrhea at the highest dose was recorded as a serious event and considered possibly related to the drug; headache, diarrhea and gas were more frequent in those receiving the highest dose. ^[2]
• 24-week trial (502 adults with obesity): During the treatment period, 78.7% of participants experienced at least one adverse event (83.2% in the placebo group). 18 people (3.6%) reported at least one serious event; according to the authors, the distribution was similar between groups. ^[2]

The FDA reads this picture differently: the authors did not give the distribution of adverse events by dose group, laboratory values or details of serious events; the intravenous studies involve few people and are very short. ^[1] The FDA’s drug safety office also states that, because of different study designs, populations and lack of case detail, it is not possible to derive a safety signal from these data. ^[1]

Cancer reports in the 12-week trial

In the 12-week trial with 300 adults with obesity, five participants reported serious events, and all five were in AOD-9604 groups: basal cell carcinoma, lipoma and squamous cell carcinoma in one dose group; breast cancer and malignant melanoma in the other two dose groups. ^[2]

According to the responsible investigator, none of these events was related to the drug. The authors’ reasons are listed as follows: no cancer was seen in the highest dose group, these people had long neglected health checkups, three cases were skin cancer and the study was conducted in Australia, where skin cancer is very common, and obesity also raises the risk of some cancers. ^[2] The FDA writes that it is concerned about these cancer reports and that there is insufficient information to decide that they were unrelated to the drug. ^[1]

What do animal toxicity studies show?

The nonclinical toxicity data rest on a single paper; one of the paper’s two authors is an executive of the developer company, and the studies were funded by the company. ^[3] The authors conclude that there is no genotoxic or toxicological concern. ^[3] The FDA, reading the same paper, considers some findings as possible safety signals. Animal doses are not given in the table because they cannot be transferred to humans.

According to the FDA, no cancer (carcinogenicity) or reproductive-developmental toxicity study has ever been done; there is also no toxicity study for the subcutaneous and dermal routes proposed on the market. ^[1] There are no data at all on safety during pregnancy and breastfeeding.

Why do the growth hormone and IGF-1 concerns matter?

According to the authors of the safety summary, long-term use of full growth hormone is associated with risks such as glucose intolerance, insulin resistance, edema and high blood pressure, and high IGF-1 levels are also debated with respect to cancer risk. ^[2] The assumption that AOD-9604 avoids these risks rests on two findings: in a study with mice, that it does not bind to the growth hormone receptor and does not stimulate cell proliferation through the receptor ^[5], and that no significant difference from placebo was reported in IGF-1 and sugar-loading tests in company trials. ^[2]

A 2026 review states that there is no established cancer signal for AOD-9604 in clinical studies, but also that there are no long-term safety data. ^[6] The FDA stresses that the molecular target and mechanism of action of the substance are unknown and that there are no human pharmacokinetic and pharmacodynamic data. ^[1] In short, the “does not behave like growth hormone” finding is short-term and indirect; what will happen with long-term use is unknown.

Injection and product quality risks

Some of the products offered for sale are subcutaneous injection vials; this route was never studied in humans. ^[1] The FDA writes that the subcutaneous route in general produces more immune response than the intravenous route, that this response can range from asymptomatic antibodies to life-threatening reactions, and that this concern applies given the 16-amino-acid structure of AOD-9604. ^[1] The disulfide bridge in the molecule can lead to degradation and aggregation of peptides; aggregation is also a risk factor for immune response. ^[1]

The certificate of analysis reviewed by the FDA lacked impurity, aggregate, microbial load and endotoxin tests; the FDA therefore considers the substance not well characterized physically and chemically. ^[1] The current FDA page also states that products containing AOD-9604 may carry a risk of immune response through some routes of administration and may be associated with serious adverse events, although causality is unclear. ^[4]

The substance is sold on the internet and has been detected in vials seized in the US. ^[7] Among the problems reported by people who self-administer unlicensed peptides targeting the growth hormone axis are hormone and metabolic disturbances, fluid retention, muscle and joint complaints and injection site reactions; this picture belongs not to a single substance but to this group of peptides. ^[6] The general framework of purity, endotoxin and sterility problems is in a separate guide: Peptide side effects

Why is the frequency of side effects unknown?

Through January 7, 2024, there were no reports for AOD-9604 used orally, subcutaneously or dermally in the FDA’s adverse event reporting system FAERS; in CAERS, the food and supplement complaint system, there were also no cases between 2004 and 2024, and no case report had been published in the literature. ^[1] The FDA’s drug safety office specifically notes that the absence of reports does not mean that the substance is safe or has no toxicity; not every event is reported to FAERS, and events with pharmacy-compounded products are especially under-reported. ^[1]

For a licensed drug, the frequency of side effects emerges from trials of thousands of people and post-licensing monitoring. The longest trial of AOD-9604 is 24 weeks, and there is no marketing authorization holder or regular safety reporting. The FDA writes that obesity is a condition requiring long-term treatment and that there is no information to support patient safety with long-term use. ^[1]

Limits of this page

This page compares published trial summaries, the toxicity paper by the company’s authors and the FDA’s 2024 assessment. Because the detailed data of the trials were not published, side effect rates cannot be given by dose group. No dose, method of use or product sourcing information is given; an unexpected symptom is a condition that should be evaluated by a physician together with the history of drug or substance use.