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AI Finds Unreported Side Effects of GLP-1 Drugs in Reddit Posts

A study of more than 400,000 posts in the social media platform Reddit has identified previously unreported side effects from the increasingly popular GLP-1 weight loss and diabetes drugs. Users reported symptoms affecting menstrual cycles and body temperature, which have not yet been described in clinical trials or included in drug labels.  

Published today in Nature Health, the study covers over five years of public online posts from nearly 70,000 Reddit users discussing their personal experience taking the GLP-1 drugs semaglutide and tirzepatide.

“Some of the side effects we found, like nausea, are well known, and that shows that the method is picking up a real signal,” says Sharath Chandra Guntuku, PhD, research associate professor in computer and information science at Penn Engineering 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.”  

Although the study is not representative of the broader population—Reddit users are generally younger, more likely male and based in the U.S.—the symptoms reported collectively match known side effects of semaglutide and tirzepatide. About 44% of users described at least one known side effect, most commonly symptoms of gastrointestinal distress. 

“Clinical trials generally identify the most dangerous side effects of drugs, but they can fail to find what symptoms patients are most concerned about,” says Lyle H. Ungar, PhD, professor in computer and information science at Penn Engineering. “Online patient communities work a lot like a neighborhood grapevine. 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. Even though social media is not necessarily representative, a large collection of posts may reflect additional concerns.” 

The study uncovered a series of side effects that were previously unreported for these drugs. This included discussions of menstrual cycle changes, such as intermenstrual bleeding, heavy bleeding, and irregular cycles. Other users reported chills, hot flashes, fever, and other temperature-related symptoms. In addition, fatigue symptoms ranked as the second most common complaint in these online posts despite rarely being reported in clinical trials. 

“We can’t say that GLP-1s are actually causing these symptoms,” says Neil K. R. Sehgal, doctoral student at the University of Pennsylvania and the study’s lead author. “But nearly 4% of the Reddit users in our sample reported menstrual irregularities, which would be even higher in a female-only sample. We think that’s a signal worth investigating.” 

While efforts to scour the internet for self-reported drug side effects have been ongoing for more than a decade, screening through social media posts at scale remained challenging until the arrival of large language models such as ChatGPT or Gemini. In particular, these tools can prove instrumental in mapping the language users use to describe their symptoms to clinical terminology defined in the Medical Dictionary for Regulatory Activities (MedDRA), used to officially report symptoms in clinical trials. 

“Large language models have made it possible to do this kind of analysis much faster with a level of standardization that could be difficult to achieve before,” says Sehgal. 

The researchers hope these findings will encourage researchers and drug developers to investigate the side effects discussed by users online. In future work, the team plans to expand beyond Reddit and English-language discussions to confirm whether the same symptoms appear across different social media platforms and populations. 

While this approach is not intended as a replacement for clinical trials, screening social media posts for clues on unreported side effects can make a significant difference in terms of speed. This can be especially relevant for drugs like semaglutide and tirzepatide, originally diabetes drugs that quickly became mainstream when the FDA granted them approval as weight loss drugs. 

“Clinical trials are the gold standard, but by design, they are slow,” says Guntuku. “The whole point of this kind of approach is that it can move quickly, and that’s exactly when it’s most valuable.”

The post AI Finds Unreported Side Effects of GLP-1 Drugs in Reddit Posts appeared first on Inside Precision Medicine.

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Opinion: I’m a MAHA activist. I went into the public health lion’s den — and it changed how I think

The past few weeks have been nothing but discouraging for those of us who helped create the Make America Healthy Again movement, including a silly executive order on glyphosate that feels anathema to what we have fought for. I’d be lying if I said that my heart hasn’t been bent toward repentance for my part in the whole thing. I helped champion Bobby Kennedy as a campaign volunteer, and when he joined up with then-candidate Donald Trump, I reluctantly decided that the trade-offs were worth what I believed Kennedy could advocate for within the walls of a Trump White House: the best fixes for a very sick and broken nation. 

Yet I found myself recently, and reluctantly, headed to the citadel of arrogance: Washington (well, Arlington, Va., to be more specific). At the invitation of Brinda Adhikari — one of the hosts of the podcast “Why Should I Trust You?” — I attended the Association of Schools and Programs of Public Health’s annual meeting, where I spoke on a panel about engaging in civil conversation in a session called “A Dialogue Between Academic Public Health and MAHA.”

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Opinion: What public health can learn from the MAHA movement

I didn’t expect to find myself face to face with leaders and activists from the “Make America Healthy Again” movement in respectful dialogue, or to consider inviting one into a public health classroom. But that’s exactly where I found myself this spring.

At a national public health meeting in March, I attended a session that brought together public health professionals, physicians, and MAHA leaders for a rare, good-faith conversation. I went out of curiosity. I left with a level of clarity I hadn’t expected — and a few unexpected connections.

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How sports betting apps hook users

For most of the last 80 years, sports betting was limited to Las Vegas. But after a 2018 Supreme Court decision loosened regulations on professional sports wagers, it became possible to place bets on games 24/7 — with nothing more than a smartphone and a bank account. 

In 2013, just five years prior to the landmark SCOTUS case, gambling was classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in a new category called “Substance-Related and Addictive Disorders.” This grouped gambling with alcohol use disorder and other addictions. Gambling is also known to have the highest suicide rate of any addiction.

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Artificial Sweeteners Could Alter Metabolism over Generations

Popular low-calorie sugar substitutes can negatively affect both the balance of microbes in the gut and gene expression in a heritable way, preclinical research suggests.

The findings in mice, published in Frontiers in Nutrition, challenge long-standing assumptions that non-nutritive sweeteners (NNS) are metabolically inert and underscore their potential to influence health across generations through microbial and molecular pathways.

Both sugar alternatives studied had an impact: sucralose, a popular artificial sweetener that is around 600 times sweeter than sugar, and stevia, a no-calorie natural alternative extracted from the leaves of a South American plant.

Lead researcher Francisca Concha Celume, PhD, from the University of Chile, said the changes seen in glucose tolerance and gene expression could be interpreted as early biological signals related to metabolic or inflammatory diseases.

“For example, the animals did not develop diabetes. Instead, what we observed were subtle changes in how the body regulates glucose and in the activity of genes associated with inflammation and metabolic regulation,” she explained.

“It is possible that such changes could increase susceptibility to metabolic disturbances under certain conditions, such as a high-fat diet.”

Celume and team divided 47 male and female mice into three groups receiving either plain water, or water with sucralose or stevia added over 16 weeks at levels comparable to those seen in a usual human diet.

These mice were then bred, with each of the two subsequent generations just receiving plain water.

The team found there were no differences in glycemic response in the initial group, but that it had mildly altered in the male offspring of those fed sucralose in both successive generations. By the second generation, female mice with stevia-consuming grandparents had elevated fasting blood sugar.

Fecal microbiomes in both sets of animals receiving sweeteners were more diverse than in those given plain water. But sweetener-fed mice also had lower levels of short-chain fatty acids, which could signal epigenetic changes and could indicate that bacteria may be generating less beneficial metabolites and that this was passed on to subsequent generations.

Mice that had consumed sucralose were particularly affected and had more pathogenic bacteria and fewer beneficial species in their fecal microbiomes. The impact of this sweetener tended to be more consistent and persistent across generations.

The researchers also examined the impact of five genes relating to inflammation, gut barrier function, and metabolism in the liver and intestines.

Overexpression in the inflammation-linked toll-like receptor-4 (tlr4) and tumor necrosis factor (tnf) genes was seen both in animals that consumed sucralose and stevia. This was also seen in the immediate offspring of the former but not the latter.

The expression of sterol regulatory element-binding protein 1 (Srepb1), which is linked with regulation of lipid and carbohydrate metabolism, was decreased in the liver of sucralose-fed animals and subsequent generations.

“In summary, our findings demonstrate that parental consumption of sucralose or stevia induces persistent, intergenerational changes in host metabolism, intestinal and hepatic gene expression, gut microbiota composition, and microbial metabolite production in unexposed offspring,” the researchers concluded.

They added: “Given the widespread use of NNS during critical developmental periods, these findings raise important questions about their safety and long-term impact.”

The post Artificial Sweeteners Could Alter Metabolism over Generations appeared first on Inside Precision Medicine.

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Cancer Drug Shortfalls Tied to How BET Inhibitors Hit BRD2 and BRD4 Differently

For more than a decade, BET inhibitors have been touted as one of cancer therapy’s most promising drug classes. The logic was straightforward: many tumors rely on oncogenes that depend on BET (bromo- and extra-terminal domain) proteins—chromatin‑binding regulators that help switch genes on. Block the BET family, the thinking went, and cancer cells should lose their transcriptional fuel. In the lab, the strategy often worked. But in clinical trials, the results were far more uneven: modest responses, substantial side effects, and little clarity about which patients might benefit.

A new study from the Max Planck Institute of Immunobiology and Epigenetics (MPI‑IE) may finally explain why. Published in Nature Genetics, the work uncovers a previously underappreciated division of labor within the BET family—one that helps clarify why drugs that block all BET proteins at once have struggled in the clinic. The paper is titled, “Histone acetylation-dependent clustering of BRD2 instructs transcription dynamics.”

Most BET inhibitors were designed to block a shared bromodomain that all BET proteins use to bind chromatin. That approach assumed the proteins—BRD2, BRD3, BRD4, and BRDT—perform similar roles. But the new study paints a more nuanced picture. Using rapid protein degradation, chemogenomics, and super‑resolution microscopy in mouse embryonic stem cells, the team dissected the distinct contributions of BRD2 and BRD4 to transcription.

Super-resolution microscopy images of cell nuclei showing BRD2 (green) and BRD4 (red) inside the nucleus. When transcription elongation is blocked with flavopiridol (right), BRD2 clusters increase markedly while BRD4 distribution shifts—visually demonstrating that the two proteins respond differently to the same perturbation, reflecting their distinct roles in initiating (BRD2) versus driving gene transcription (BRD4). [MPI of Immunobiology & Epigenetics, Asifa Akhtar]

Their findings reveal that BRD4 drives the well‑known step of releasing paused RNA polymerase II into productive elongation. BRD2, however, acts earlier. It helps recruit and organize the transcription initiation machinery at promoters, particularly under conditions where pause‑release is impaired. As the authors wrote, BRD2’s role becomes “particularly critical under the conditions of impaired pause release,” a mechanistic insight that reframes how BET proteins collaborate during gene activation.

The MPI‑IE team likens BRD2 to a stage manager. “BRD2 sets up the stage: assembling the props, costumes, and actors to ensure preparations run smoothly. BRD2 then gives BRD4, the actor, the ‘start’ signal to begin with the performance,” said senior author Asifa Akhtar, PhD. Blocking both proteins simultaneously—exactly what current BET inhibitors do—disrupts two different steps of transcription at once, producing unpredictable and context‑dependent effects.

“Our data shows that the setup work happening before is just as critical for gene activation,” explained Akhtar.

A key discovery is that BRD2’s recruitment depends on histone H4 acetylation placed by the enzyme MOF. When MOF was rapidly depleted or deleted, BRD2 lost its grip on chromatin, while BRD3 and BRD4 remained largely unaffected. “The findings support a model in which acetylated chromatin creates a platform that allows regulatory proteins like BRD2 to concentrate and prepare the transcription machinery,” noted first author Umut Erdogdu, PhD.

The team also showed that BRD2 forms dynamic clusters at promoters. Removing only the BRD2 region responsible for clustering stalled transcription almost as completely as deleting the entire protein.

The study suggests a path forward: instead of blocking all BET proteins indiscriminately, future therapies may need to distinguish between BRD2‑ and BRD4‑specific functions. “Thus, these findings support a model in which histone acetylation-dependent spatiotemporal dynamics of BRD2 coordinate the transcription machinery to regulate transcription initiation,” the authors wrote.

For a field long puzzled by the uneven performance of BET inhibitors, BRD2’s newly revealed role offers a compelling piece of the puzzle—and a clearer blueprint for next‑generation cancer therapeutics.

The post Cancer Drug Shortfalls Tied to How BET Inhibitors Hit BRD2 and BRD4 Differently appeared first on GEN – Genetic Engineering and Biotechnology News.