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An artificial intelligence analysis of nearly 150,000 Reddit posts and comments has uncovered unexpected symptom reports among people claiming to use unapproved versions of retatrutide, an experimental weight-loss drug that has not yet received regulatory approval.
The study, led by researchers at the University of Pennsylvania and published in JAMA Network Open, found that increased appetite was the most commonly reported symptom among users whose complaints could be classified medically. The finding was unexpected because retatrutide is designed to help regulate appetite and reduce body weight.
The researchers cautioned that the findings do not establish new side effects or prove that the drug caused the reported symptoms. Products sold through unregulated online channels may differ in ingredients, purity and dosage, making it difficult to determine what users are actually taking.
The team analysed nearly 150,000 Reddit posts and comments from around 40,000 users. Of these, approximately 14,000 claimed to have personally used an unapproved version of retatrutide.
After excluding expected effects such as weight loss and reduced appetite, the researchers identified 7,823 users who reported at least one symptom that could be classified using standard medical terminology.
“AI helps us find recurring patterns in people’s self-reports, including experiences that may be missed by conventional drug-safety monitoring,” said Sharath Chandra Guntuku, a research associate professor at the university’s Department of Computer and Information Science and senior author of the study.
Retatrutide belongs to a new generation of weight-loss medicines that act on hormone receptors involved in appetite regulation and metabolism. Unlike semaglutide, which targets one receptor, and tirzepatide, which targets two, retatrutide activates three.
Clinical trials of retatrutide have primarily identified digestive problems as common side effects. The increased appetite reported in online discussions therefore stood out to researchers, although it remains unclear whether the accounts reflect the effects of genuine retatrutide or other substances in unregulated products.
“We can’t say that retatrutide is causing these symptoms, or even that Reddit users are actually taking genuine retatrutide, since the drug is not legally available, and gray market formulations vary,” said Lyle Ungar, a professor in computer and information science and co-author of the study.
The research builds on an earlier investigation by the same team that used large language models to examine more than 400,000 Reddit posts about semaglutide and tirzepatide. That study identified reports of potential side effects, including menstrual irregularities, that merited further investigation.
For the latest study, AI tools extracted users’ descriptions of symptoms and converted them into standardised medical terminology, allowing researchers to identify patterns across a large volume of online discussions.
“This is the first glimpse into the experiences of a population that is otherwise outside conventional drug safety monitoring because they are taking unapproved versions of a drug that has yet to finish clinical trials,” said Neil Sehgal, the study’s first author and a doctoral student in computer and information science.
The researchers said the findings should be treated as a starting point for further investigation rather than evidence of confirmed adverse effects. They added that AI-assisted analysis of online discussions could help identify potential safety concerns that warrant testing through more rigorous research.