Penn Researchers Use AI on Reddit Posts to Probe Unapproved Retatrutide

Analyzing 150,000 posts at scale

Retatrutide is not yet approved for use, but online forums show that people are buying unapproved versions, which are not intended for human consumption, and sharing their experiences. The Penn team analyzed nearly 150,000 posts and comments from roughly 40,000 Reddit users.

According to the university, the researchers used AI to identify approximately 14,000 users who described personally taking an unapproved version of retatrutide. The AI tools then extracted the symptoms those users attributed to the drug and matched the descriptions to standardized medical terminology. That left 7,823 users reporting at least one classifiable symptom beyond expected effects such as weight loss or appetite suppression.

"A researcher might be able to examine a few thousand Reddit posts by hand, but looking at nearly 150,000 would be an enormous undertaking," said Neil Sehgal, the study's first author and a doctoral student in Computer and Information Science (CIS).

Increased appetite stands out

Among users who shared classifiable symptoms, the most frequently reported was increased appetite. This differs from retatrutide's Phase 2 clinical trials, where gastrointestinal complaints such as nausea were the most common side effects. The drug is currently in Phase 3 trials, the final step before FDA approval. The team described the appetite finding as unexpected given the weight-loss effects shown in Phase 2.

The researchers also compared the results with their earlier study of semaglutide and tirzepatide. Reddit posts about gray-market retatrutide featured proportionally more reports of appetite-related symptoms, sleep disturbances, increased heart rate and muscle-related changes, and fewer reports of nausea and other gastrointestinal symptoms.

The team notes that semaglutide activates one hormone receptor involved in regulating appetite and blood sugar, tirzepatide activates two, and retatrutide activates three. That gave them reason to look for a different pattern of symptoms.

Strong caveats from the authors

The researchers stress that the findings should be treated with caution. "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 CIS professor and co-author.

Co-author Jena Shaw Tronieri, of Penn's Center for Weight and Eating Disorders, pointed out that users who obtain an unapproved medication on the gray market likely differ from clinical populations. Some may take multiple experimental peptides, and what they take cannot be verified. "We need more research to understand what, if anything, these differences in self-reported symptoms mean," she said.

The results are meant as a starting point for other public health researchers, not as evidence of previously unrecognized side effects.

Looking for early safety signals

The study builds on earlier Penn work that used large language models to analyze more than 400,000 Reddit posts about semaglutide and tirzepatide. That work identified potential side effects, including menstrual irregularities, that may not have been fully captured in clinical trials or regulatory documents. Another research group later examined the same symptoms in the FDA's adverse-event database. Its study, published in Obstetrics & Gynecology, also found disproportionate reports of certain menstrual changes.

"Other researchers can take what we find on Reddit and look for the same patterns in other datasets, using entirely different methods," Sehgal said. Sharath Chandra Guntuku, the senior author and director of Penn's Computational Social Listening Lab, said the goal is to identify hypotheses that can be tested, including experiences that conventional drug-safety monitoring may miss.

The work was conducted at Penn's School of Engineering and Applied Science and Perelman School of Medicine, with Benjamin Rader of Boston Children's Hospital as an additional co-author. It was funded in part by the Penn Medical Communication Research Institute. Tronieri reports a grant from Novo Nordisk and consulting fees from Currax Pharmaceuticals, LLC. The other authors report no conflicts of interest.