Penn’s AI study finds increased hunger tops Reddit symptom reports for an unapproved drug

University of Pennsylvania researchers used AI to examine nearly 150,000 Reddit posts and comments about unapproved retatrutide, an experimental weight-loss drug. Increased appetite topped the classifiable symptoms reported by users claiming to take it. The study, published in JAMA Network Open, offers leads for safety research—not evidence that the drug caused those experiences.

Following users outside clinical trials

Retatrutide remains in phase 3 trials and is not approved for use. Yet people are buying unapproved versions online, including formulations not intended for human consumption, and discussing their experiences. That creates a population outside conventional drug-safety monitoring, according to first author Neil Sehgal, a Penn doctoral student in computer and information science.

The team had previously used large language models—the technology behind many chatbots—to study more than 400,000 Reddit posts about semaglutide and tirzepatide. Researchers applied the same approach to gray-market retatrutide. Unlike those drugs, which activate one and two hormone receptors respectively, retatrutide activates three, giving the team a reason to investigate whether symptom patterns might differ.

The analysis covered roughly 40,000 Reddit users. AI tools identified approximately 14,000 who described personally taking an unapproved version of retatrutide. They then extracted symptoms users attributed to the product and mapped informal descriptions to standardized medical terms. This let researchers group similar experiences even when people described them in different words.

After excluding expected effects such as weight loss and reduced appetite, the researchers retained 7,823 users who reported at least one medically classifiable symptom. The most-common-symptom finding applies to this selected group, rather than everyone in the Reddit dataset or everyone taking the experimental medication.

A different pattern from the trials

The appetite finding contrasted with retatrutide’s phase 2 trials, where gastrointestinal complaints, including nausea, were the most common side effects. It was also unexpected given the drug’s intended appetite-suppressing effects and the weight loss demonstrated in clinical testing. The Reddit analysis, however, did not compare verified use of identical products across equivalent patient groups.

Compared with the team’s earlier Reddit analyses of semaglutide and tirzepatide, retatrutide discussions contained proportionally more reports of appetite changes, sleep disturbances, increased heart rate and muscle-related symptoms. Nausea and other digestive complaints appeared proportionally less often. These were differences in self-reported symptom patterns, not a clinical finding that one drug was safer than another.

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.

Lyle Ungar, Penn computer and information science professor and study co-author

Co-author Jena Shaw Tronieri identified several possible explanations. Retatrutide’s different biological action could matter, but so could the people choosing to obtain an unapproved drug. Some may be taking multiple experimental peptides. Unregulated products can also vary in ingredients, purity and dosage, making the medicine itself only one possible source of the observed differences.

The next step is another dataset

For the researchers, AI’s contribution was scale: extracting recurring patterns from a volume of conversation that would be difficult to examine manually. Senior author Sharath Chandra Guntuku described the goal as generating testable hypotheses, including experiences that conventional safety monitoring might miss. Confirmation requires evidence beyond the posts themselves.

There is a precedent for that next step. The team’s earlier work flagged menstrual-irregularity reports around semaglutide and tirzepatide. Another group subsequently examined related symptoms in the FDA’s adverse-event database and also found disproportionate reports of certain menstrual changes. That follow-up did not establish causation, but it supplied another reason to investigate. Sehgal hopes researchers will similarly test the retatrutide patterns using independent datasets and different methods.