Are some GLP-1 side effects being overlooked?

For the study, researchers from the University of Pennsylvania used AI to analyze over 410,198 Reddit posts from 67,008 users that mentioned the GLP-1 drugs semaglutide or tirzepatide between May 2019 and June 2025.

Of the users who reported using GLP-1s, 43.5% said they experienced at least one side effect. The most common side effects were gastrointestinal symptoms, such as nausea (36.9%), fatigue (16.7%), vomiting (16.3%), constipation (15.3%), and diarrhea (12.6%).

However, researchers also identified symptoms that may be potentially overlooked, including reproductive and temperature-related symptoms. Almost 4% of users reported reproductive side effects, including irregular menstrual cycles, intermenstrual bleeding, and heavy bleeding. Other users reported chills, feeling cold, hot flashes, and fever-like sensations.

"Some of the side effects we found, like nausea, are well known, and that shows that the method is picking up a real signal," said Sharath Chandra Guntuku, a research associate professor in computer and information science at Penn and the study's senior author. "The underreported symptoms are leads that came from patients themselves, unprompted, and clinicians could potentially pay attention to them."

"These drugs are thought to work by engaging part of the brain called the hypothalamus, which helps regulate a wide variety of hormones," said Jena Shaw Tronieri, a senior research investigator at Penn's Center for Weight and Eating Disorders and one of the study's authors. "That doesn't mean the medications are necessarily causing these symptoms, but it could suggest that reports of menstrual changes and body temperature fluctuations are worth studying more systematically."

Although gastrointestinal symptoms are the most common side effects associated with GLP-1 drugs, patients have reported multiple other side effects, including unintended muscle mass loss, nutritional deficiencies, a potential for increased risk of miscarriage or birth defects, and severe mental health issues like depression and suicidal thoughts. Recent research also suggests GLP-1s may be linked to osteoporosis or gout, as well as a rare eye condition called ischemic optic neuropathy that can cause sudden or partial blindness in one or both eyes. 

They also noted that the population of their study is not representative of all GLP-1 users. Reddit users are typically younger, more likely to be male, and based in the United States. In the future, the researchers hope to expand their work beyond Reddit and English-language communities to determine if the same symptoms also appear across different platforms and populations. 

"We don't really know yet whether what we're seeing on Reddit reflects the experience of GLP-1 users globally, or whether it's particular to the kind of person who posts on Reddit in the United States," Ungar said.

The researchers also hope that their findings will encourage clinicians and other researchers to pay more attention to the side effects patients are discussing online.

"Online patient communities work a lot like a neighborhood grapevine," Ungar said. "People who are living with these medications are swapping notes with each other in real time, sharing experiences that rarely make it into a doctor's office visit or an official report."

These side effects are "clearly on patients' minds, and that's worth paying attention to," Sehgal added.