A new analysis of GLP-1 side effects from a Reddit study of 400,000 posts has identified a cluster of symptoms (fatigue, menstrual irregularities, hot flashes and chills) that rarely feature on official drug labels, raising questions about what patients are actually experiencing on these medications. The research, published in Nature, used AI to comb through more than five years of posts from 67,008 users discussing semaglutide (Ozempic, Wegovy and Rybelsus) and tirzepatide (Mounjaro and Zepbound).
The study did not conclusively prove that GLP-1 medications caused these symptoms. It established a link, and the researchers themselves acknowledged that some effects may stem from weight loss rather than the drugs. Still, they wrote that their findings ‘highlight patient concerns not well captured in current labelling or trials.’
What the GLP-1 side effects Reddit study actually found
Gastrointestinal complaints (nausea, vomiting, constipation and diarrhoea) remain the most widely reported problems, and the study confirmed that. The more eyebrow-raising finding was the range of symptoms sitting alongside them: fatigue, menstrual changes, chills and hot flashes, each reported by users who might have assumed they were unrelated to their medication.
According to Penn Engineering, nearly 4% of the Reddit users in the sample reported menstrual irregularities, a figure the researchers noted would be even higher in a female-only sample. That is a substantial signal from an unsolicited, unfiltered data source. When patients are typing their experiences into a forum rather than filling out a clinical form, they tend to report what they actually notice.
Separate research from Natural Cycles adds further weight to this picture. In that study, 27% of all respondents reported noticing changes to their menstrual cycle since starting GLP-1 treatment. Among those actively using a GLP-1 for weight loss, 43% had noticed cycle changes. These are not marginal numbers.
Hormones, weight loss and the question of cause
Untangling what is driving these symptoms is not straightforward. Much of what gets attributed to GLP-1 medications may actually be a consequence of rapid weight loss, which the drugs can produce at up to 20% of body weight over 72 weeks. Mir Ali, who is quoted in the original reporting, notes that many changes ‘are tied to changes in hormones.’ Studies have found that circulating oestrogen levels typically drop in women who lose significant amounts of weight, while testosterone levels in men tend to increase.
Kelley Gregorovic, also quoted in the reporting, says menstrual changes ‘make the most sense to me clinically’ of all the side effects flagged. Recent analyses of FDA adverse event reports have found menstrual changes with some GLP-1 medications, including heavier bleeding, blood clots and bleeding between periods. ‘That still doesn’t prove the medication is causing them,’ Gregorovic says, ‘but it tells us this is something worth paying attention to and studying further.’
Age compounds the picture further. A KFF survey cited in the original reporting found that GLP-1 use is highest in women between the ages of 50 and 64, with the second highest group being 30 to 49. Those are precisely the years when perimenopause typically begins. As Gregorovic puts it: ‘Her weight may be changing, her metabolic health may be changing, and her hormones may be changing, all at the same time.’ Separating medication effect from life stage is a genuine clinical challenge.
Fatigue, chills and hot flashes
Fatigue is the other symptom that practitioners say they hear about regularly. GLP-1s suppress appetite strongly, and if that suppression leads to inadequate calorie or protein intake, tiredness follows. Gregorovic’s approach is methodical: she asks patients whether they are eating enough, hydrating, getting enough protein and sleeping well before looking further. If those answers check out and fatigue persists, she orders lab work for anaemia, nutritional deficiencies and thyroid dysfunction.
Hot flashes and chills sit on shakier ground. Ali says it is not a common complaint he receives. Rutuja Patel, also quoted in the reporting, agrees these effects are not very common, and suggests that loss of body fat, which provides insulation, could leave people feeling colder more easily. That is a plausible mechanism, but one that still needs proper investigation.
The consistent message from the clinicians quoted throughout this reporting is that no new symptom should be dismissed, but none should be automatically attributed to the drug either. If menstrual irregularity does not settle within one to two cycles, Patel says patients should also raise it with their gynaecologist. And as Gregorovic puts it plainly: ‘When patients repeatedly tell us, “Something changed when I started this medication,” I think we should listen.’
