Reproductive symptoms, temperature-related complaints, and psychiatric symptoms were among the side effects of GLP-1 drugs reported in an analysis of Reddit posts.
“Clinical trials tell us a lot, but they’re conducted under very controlled conditions with carefully selected participants,” Neil Sehgal, a doctoral student at the University of Pennsylvania School of Engineering and Applied Science, Philadelphia, told Medscape Medical News. “At the same time, millions of patients are using Reddit every day and sharing very detailed accounts of their experiences with these medications.”
To investigate signals that the medical community “might be missing or underappreciating,” Sehgal and colleagues developed an AI-based system to automatically extract and categorize symptoms from Reddit posts at scale.
The analysis of more than 400,000 posts identified more than 67,000 people who reported taking a GLP-1. In addition to menstrual changes and temperature-related complaints, “the psychiatric symptoms were notable,” Sehgal said. “About 13% of users reporting side effects mentioned something in the psychiatric category, such as anxiety, insomnia, or depression.”
“Fatigue was the second most commonly reported symptom overall but has met relatively few reporting thresholds in existing trials,” he added. “This gap between what patients are self-reporting online and what gets captured in trials is really what motivated this whole line of work.”
The study was published online as a brief communication on April 10 in Nature Health.
‘Signals Worth Investigating’
The researchers conducted a cross-sectional study of self-reported side effects of semaglutide and tirzepatide using Reddit data from May 2019 through June 2025.
Reddit was selected as the data source “due to its large, publicly accessible, topic-specific health communities and its long-form, context-rich user discussions,” the authors wrote.
Posts/comments were collected from nine large subreddits that discussed GLP-1s or weight management.
In total, the team analyzed 410,198 posts and identified 67,008 users who self-reported using these medications; 43.5% described at least one side effect.
Gastrointestinal symptoms predominated, including nausea (36.9%), fatigue (16.7% ), vomiting (16.3%), constipation (15.3%), and diarrhea (12.6%). The fact that these commonly reported symptoms were also reported in Reddit showed that the analysis was picking up real signals, according to the authors.
Other symptoms reported by ≥ 5% of users who disclosed side effects included decreased appetite, abdominal pain, gastroesophageal reflux, headache, abdominal distension, and dizziness. The most frequent co-occurring side effects were nausea and vomiting, with 2917 users (10.0%) self-reporting both.
Close to 4% of users with side effects reported reproductive symptoms — for example, menstrual changes like intermenstrual bleeding (0.9%), heavy bleeding (0.9%), and irregular cycles (0.7%).
“These symptoms aren’t prominently featured in the current prescribing information,” Sehgal said. “When you consider that we're looking at a mixed-gender sample on Reddit, and that Reddit skews male, the true rate among women taking these medications could potentially be higher.”
Although the study findings are not causal, the menstrual findings in particular “is a signal worth investigating,” he added.
A sub-analysis of the 29,172 users who disclosed at least one side effect and mentioned a specific formulation found that 17,937 (61.5%) exclusively mentioned semaglutide formulations, and 7125 (24.4%) exclusively mentioned tirzepatide formulations.
Exploratory descriptive analyses compared side effect frequencies between the formulations. Among semaglutide users, the most commonly reported symptoms were nausea (39.4%), fatigue (16.1%), vomiting (18.0%), constipation (14.9%), and diarrhea (12.4%).
Among tirzepatide users, the most commonly reported symptoms were similar: nausea (28.6%), fatigue (14.7%), vomiting (11.1%), constipation (12.9%), and diarrhea (12.5%). However, injection site reactions, myalgia, insomnia, and temperature-related symptoms (chills, feeling cold) were also reported by 1%-4% of tirzepatide users.
The authors acknowledged that patients using weight-loss subreddits may differ from the overall population prescribed GLP-1s. Specifically, Reddit users tended to be younger, were more likely to be men, and were disproportionately located in the US.
Given the limited generalizability, the results “should be interpreted as hypothesis-generating signals that require confirmation through traditional surveillance systems and prospective studies in representative populations, the authors wrote.
In addition, because users were not prompted to disclose all side effects, the authors could not estimate their true prevalence.
Nevertheless, “If patients on these medications come to you reporting menstrual irregularities, temperature-related symptoms like chills or hot flashes, or fatigue, take those reports seriously,” Sehgal advised. “These aren’t prominently featured in current prescribing information, but our data suggest they may be real and more common than the labeling implies. They’re worth documenting and worth asking about.”
‘No Changes to Clinical Practice Warranted Now’
Commenting on the study for Medscape Medical News, Vivek Rudrapatna, MD, PhD, an inflammatory bowel disease specialist at the University of California, San Francisco, said, “The idea of using AI and large language models to mine social media data to identify and prioritize potential findings on drug effects is a very worthy goal. These methods are getting better at information retrieval and synthesis.” Rudrapatna was not involved in the study.
“A well-designed approach that blends ‘real-time’ analytics with other data from clinical trials, basic mechanistic studies, etc. has great potential to discover true and important signals faster than conventional clinical studies,” he added.
That said, he noted, “This study hasn’t raised any serious new adverse events (AEs) that warrant changes to clinical practice right now. The rates appear to be very low, particularly among an online population that is enriched for reporting AEs (if patients don’t experience AEs they’re less likely to report them on a voluntary platform like this); none of these AEs appear to meet the standard of seriousness (eg, requiring hospitalization or urgent treatment due to being life threatening or causing significant disability); and we don’t know the rates of these events in a placebo group, so it’s hard to attribute them to the drug.”
“Retrospective clinical studies using target trial emulation methods can be used to further vet the AEs described here, identify new ones, explore mechanisms of action, and potentially identify subgroups who are most prone to them,” he concluded.
No funding was disclosed. Sehgal declared having no conflicts of interest.Rudrapatna’s research was partially funded by grants to UCSF from the following for-profit entities: Janssen, Merck, Genentech, Alnylam, Takeda, BeOne, Mitsubishi Tanabe, Stryker, and Blueprint Medicines. He reported also being a shareholder in ZebraMD and DataUnite and receiving an honorarium from Natera and Ironwood Pharma.
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