Retatrutide is an experimental weight-loss drug that targets three hormone receptors involved in regulating appetite, blood sugar, and metabolism. Unlike existing GLP-1 medications, its triple-action approach has shown promising results in clinical trials, although questions remain about its long-term safety and potential side effects. Credit: Shutterstock

An AI analysis of nearly 150,000 Reddit posts and comments offers the first systematic look at symptoms people attribute to gray-market retatrutide, showing how social media could guide drug safety research.

People are buying unapproved versions of retatrutide, a next-generation GLP-1 weight-loss drug, and sharing their experiences on Reddit before the drug has received approval for use. The products they describe taking are not intended for human consumption, but their posts offer researchers a way to examine experiences that conventional drug-safety monitoring may miss.

Researchers at the University of Pennsylvania used AI to analyze nearly 150,000 posts and comments from roughly 40,000 Reddit users, producing the first systematic look at the potential symptoms reported by people claiming to take these unapproved products. In their study, published in JAMA Network Open, increased appetite was the most frequently reported symptom among users whose reports could be classified, after expected effects such as weight loss and appetite suppression were excluded.

That finding contrasts with retatrutide’s Phase 2 clinical trials, which demonstrated weight-loss effects and identified nausea and other gastrointestinal complaints as the most common side effects. The drug is currently in Phase 3 trials, the final stage of clinical testing before possible FDA approval. The Reddit accounts, however, cannot establish that retatrutide caused the reported symptoms or that these users’ experiences reflect those of clinical trial participants.

“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,” says Lyle Ungar, a professor in Computer and Information Science (CIS) at Penn and a study co-author.

From left: co-authors Lyle Ungar, Neil Sehgal and Sharath Guntuku. Credit: Sylvia Zhang, Penn Engineering

More sleep complaints, fewer nausea reports

Retatrutide also acts differently from the better-known drugs semaglutide and tirzepatide. Semaglutide activates one hormone receptor involved in regulating appetite and blood sugar, while tirzepatide activates two. Retatrutide activates three, giving the researchers a reason to investigate whether reports from people claiming to use it might show a different pattern of symptoms.

Compared with the team’s earlier analysis of Reddit discussions about semaglutide and tirzepatide, posts about gray-market retatrutide contained proportionally more reports of appetite-related symptoms, sleep disturbances, increased heart rate, and muscle-related changes. Reports of nausea and other gastrointestinal symptoms were proportionally less common.

The researchers found that self-reported symptoms differed on Reddit between people claiming to take gray-market retatrutide and those claiming to take the approved GLP-1s semaglutide and tirzepatide. Credit: Computational Social Listening Lab

“Retatrutide works differently from existing GLP-1 drugs, so it’s possible that its effects on the body are different, too,” says Jena Shaw Tronieri, a senior research investigator at Penn’s Center for Weight and Eating Disorders and a study co-author.

“But the people discussing it on Reddit also may be different,” she notes. “Users willing to obtain an unapproved medication on the gray market likely differ from other clinical populations. Some may be taking multiple experimental peptides, and we can’t verify exactly what they’re taking. We need more research to understand what, if anything, these differences in self-reported symptoms mean.”

AI turns Reddit posts into symptom data

To identify accounts of personal use within the larger Reddit dataset, the researchers used AI tools to find users who described taking an unapproved version of retatrutide. Approximately 14,000 users met that description. The tools then extracted symptoms those users attributed to the product and matched their descriptions to standardized medical terminology. After excluding expected effects such as weight loss and appetite suppression, the analysis included 7,823 users who reported at least one classifiable potential symptom.

Neil Sehgal, a doctoral student in CIS, used AI to analyze roughly 150,000 Reddit posts about gray-market versions of retatrutide, a new, unapproved GLP-1. Credit: Sylvia Zhang, Penn Engineering

“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,” says Neil Sehgal, the study’s first author and a doctoral student in CIS at Penn. “AI makes it possible to analyze these conversations at scale, identifying patterns in what people are sharing that would otherwise be difficult to recognize.”

The approach grew out of the Penn team’s earlier work using large language models, or LLMs, to examine more than 400,000 Reddit posts about semaglutide and tirzepatide. That analysis identified potential side effects, including menstrual irregularities, that may not have been fully captured in clinical trials or regulatory documents. “We wanted to apply the same methodology to gray-market retatrutide,” says Sehgal.

Reddit clues need independent testing

The new results should be treated as leads for further research, rather than evidence of previously unrecognized side effects. “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,” says Sehgal.

Sehgal, at right, demonstrates the process used in the research: leverage AI to analyze posts and comments on Reddit about taking an unapproved GLP-1. Credit: Sylvia Zhang, Penn Engineering

“Our goal is to identify hypotheses in online conversations that we could test. AI helps us find recurring patterns in people’s self-reports, including experiences that may be missed by conventional drug-safety monitoring,” says Sharath Chandra Guntuku, a research associate professor in CIS, director of Penn’s Computational Social Listening Lab, and the paper’s senior author.

The researchers hope this approach can identify potential safety concerns earlier and give clinicians and public health researchers a starting point for investigation. Sehgal points to what happened after the team reported menstrual irregularities in its earlier GLP-1 study. Another research group was inspired to examine the same symptoms using the FDA’s adverse-event database. Its subsequent study in Obstetrics & Gynecology also found disproportionate reports of certain menstrual changes, adding evidence that those symptoms merit investigation.

“That’s what we hope will happen with this study,” says Sehgal. “Other researchers can take what we find on Reddit and look for the same patterns in other datasets, using entirely different methods. Whether those signals hold up or not, the goal is to build a better understanding of what people are actually experiencing.”

Reference: “Self-Reported Adverse Effects Among Social Media Users Taking Nonapproved Retatrutide” by Neil K. R. Sehgal, Jena Shaw Tronieri, Benjamin Rader, Lyle Ungar and Sharath Chandra Guntuku, 14 October 2026, JAMA Network Open.
DOI: 10.1001/jamanetworkopen.2026.38929

This project was funded in part by the University of Pennsylvania’s Penn Medical Communication Research Institute.

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