Top of the morning to you. The middle of the week is upon us and, since you made it this far, why not forge ahead? After all, there is always light at the end of the proverbial tunnel. You never know what you may accomplish. So please join us as we celebrate this notion with a cup or three of delicious stimulation. Our choice today is chocolate raspberry. Meanwhile, we have assembled the latest menu of tidbits to help you along. So please dig in. Have a smashing day, and please feel free to forward any secrets you come across. Our “in basket” is always open. …
The U.S. Food and Drug Administration asked Eli Lilly for more data on liver injury linked to its newly approved obesity pill, Reuters says, citing a letter posted on the agency website. The April 1 letter also said Lilly must conduct post-marketing trials to assess risks related to cardiovascular events and delayed gastric emptying. The drugmaker is required to also conduct a milk-only lactation study in lactating women who have received a dose of the pill to assess concentrations of the drug in breast milk using a validated assay. The weight loss pill, branded Foundayo, a once-daily oral medication that targets the GLP-1 hormone, won approval earlier this month under the Commissioner’s National Priority voucher program, which aims to speed FDA decisions on drugs deemed critical to public health or national security.
AbbVie, Novartis, AstraZeneca, and the Pharmaceutical Research & Manufacturers of America, the industry trade group, notched a victory after a U.S. appeals court vacated an order rejecting their request to block a Maryland drug discount law, remanding the decision for review, Bloomberg Law reports. The U.S. Court of Appeals for the Fourth Circuit ruled that a lower court erred when it denied a motion filed by the companies and the trade group for a preliminary injunction against a Maryland law. H.B. 1056, currently in effect, requires manufacturers to distribute discounted drugs to an unlimited number of pharmacies that contract with health providers under the 340B Drug Discount Program. They argued the law improperly forces drug companies to supply so-called contract pharmacies as part of the program, and that the law is illegal because it is preempted by federal law and also violates the U.S. Constitution.
Study objectivesEmerging evidence suggests a possible link between anorexia nervosa (AN) and alterations in the gut microbiota. This study aimed to characterize the gut microbiota profile in a cohort of Chinese female patients with AN.MethodA comparative analysis of the gut microbiota was conducted between 30 female patients with AN and 30 sex- and age-matched healthy controls (HCs). Fecal samples were collected for 16S rRNA gene sequencing analysis. All participants were assessed using the Eating Disorder Inventory (EDI) and the Childhood Trauma Questionnaire (CTQ). Bioinformatics analysis was performed using QIIME2, and statistical analyses were carried out with SPSS 26.0 and R software. Correlations between microbiota differences and body mass index (BMI), EDI, and CTQ were further investigated.ResultsThe analysis revealed differences in beta diversity and the abundances of specific microbial taxa between the two groups; however, no significant differences were observed in alpha diversity nor in the associations between gut microbiota and BMI, disease severity, or childhood trauma.ConclusionsThis study identified limited differences in the gut microbiota composition between patients with AN and HCs. Critically, no robust associations between gut microbiota and clinical features were found after rigorous multiple comparison correction. While nominal (uncorrected) correlations were observed between the specific microbiota and psychological traits, these results are exploratory and should be considered hypothesis-generating. They highlight a potential avenue for future research but require validation in larger, longitudinal cohorts to determine their reproducibility and biological significance.
Studying mice, researchers at Toronto’s Sinai Health have found that semaglutide—the active ingredient in popular weight loss drugs that mimic the gut hormone GLP-1—acts directly on a subset of liver cells to improve organ function, and does so independently of weight loss. The finding challenges long-held assumptions about how GLP-1 medicines work in the liver and could reshape how physicians treat metabolic liver disease.
For years, the liver benefits of semaglutide have puzzled scientists. “Glucagon-like peptide-1 (GLP-1) medicines improve metabolic liver disease through weight-loss-dependent and -independent actions,” the authors wrote. The drug was known to lower blood sugar and promote weight loss, but patients’ livers were improving in ways that those effects alone could not explain. And as the authors further noted, “The therapeutic scope of GLP-1 medicines extends beyond glycemic control and weight loss, with benefits evident in people with atherosclerotic heart disease, heart failure with preserved ejection fraction (HFpEF), peripheral artery disease, diabetic kidney disease, knee osteoarthritis, and obstructive sleep apnea (OSA).” However, as the team further pointed out, “… the mechanisms by which GLP-1 medicines improve organ dysfunction remain incompletely understood.”
Drucker has been at the forefront of GLP-1 research since the 1980s when his pioneering discoveries helped lay the groundwork for the development of GLP-1 medicines. After transforming treatment of type 2 diabetes and obesity, semaglutide and other GLP-1 medicines have been approved for other conditions including MASH (metabolic dysfunction-associated steatohepatitis). MASH is a severe form of fatty liver disease in which fat build-up, inflammation, and tissue scarring can lead to cirrhosis and liver failure. It affects about 25% Canadian adults and because it is closely linked with obesity and type 2 diabetes, treatment typically includes lifestyle interventions to reduce weight. “The approval of semaglutide for MASH highlights the importance of understanding the hepatoprotective mechanisms of GLP-1 action,” the investigators stated.
Drucker and colleagues have now found that semaglutide acts directly on the liver to reduce inflammation and scarring and improve organ function in a way that is independent of weight loss. Their finding overturns a prevailing assumption in the field that liver cells do not carry the receptor that semaglutide binds to, meaning the drug had no direct route to the organ.
Postdoctoral researcher Maria Gonzalez-Rellan, PhD, spearheaded the work that combined sophisticated mouse models of MASH with deep molecular analyses of liver cells. Her work identified two cell types carrying semaglutide receptors: liver sinusoidal endothelial cells (LSECs) and immune T cells. Although LSECs account for only about 3% of liver cell volume, they proved to be the key driver of semaglutide’s liver benefits.
A pioneer in GLP-1 biology, Daniel Drucker, MD, has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today’s widely popular medications for type 2 diabetes and obesity. Drucker’s ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]
LSECs line the tiniest blood vessels in the liver and are studded with pores that allow them to act as a molecular sieve, filtering substances passing between the liver and the bloodstream. Gonzalez-Rellan showed that semaglutide reversed MASH in mice that lacked the brain receptors controlling appetite, demonstrating that weight loss is not required for liver benefits. “Unexpectedly. semaglutide improves hepatic inflammation, fibrosis, and immune remodeling through actions on Glp1r+ pericentral liver sinusoidal ECs (LSECs) independent of changes in body weight (BW),” the team reported. “… we leveraged a unique model of GLP-1R deficiency, Glp1rWnt1-/- mice, which are resistant to GLP-1RA-induced weight loss. Remarkably, semaglutide markedly improved hepatic steatosis, fibrosis, and immune remodeling in the absence of weight reduction.”
In a further test, mice lacking LSEC receptors showed no liver improvement on semaglutide even after losing 20% of their body weight. Detailed molecular analyses of liver cell types showed that semaglutide shifts gene activity in LSCEs, prompting them to release anti-inflammatory molecules that act on the broader liver environment, pushing it toward a state more closely resembling a healthy, disease-free liver. “Together, the data using mouse models of MASH reveal an EC-specific, weight-loss-independent, semaglutide-regulated, GLP-1R-dependent intrahepatic network for improving liver health,” the scientists said.
“It turns out that the receptor responsible for these benefits is in a very specialized population of liver cells,” commented Drucker, who is also a professor of medicine at the University of Toronto. “And this receptor orchestrates the production of molecules that talk to many different types of liver cells to calm down the inflammatory environment that is the problem in metabolic disease.”
The findings carry practical implications. GLP-1 medicines have become widely prescribed, yet their mechanism of action in the body, beyond appetite suppression and blood sugar control, have remained incompletely understood. Knowing that semaglutide improves liver health independently of weight loss could influence prescribing decisions. “We’ve seen in clinical trials that patients who lose very little weight see the same reductions in liver inflammation, scarring and enzyme levels as those who lose a great deal of weight. Now we know why,” Drucker pointed out. In their paper the team concluded “Hence, semaglutide produces a broad proteomic remodeling of the liver, enabling restoration of metabolic homeostasis and suppression of fibrogenic and inflammatory programs. The strong concordance between single-cell transcriptional changes, bulk tissue proteomics, and biomarker signatures underscores the breadth of GLP-1R-mediated hepatic reprogramming.”
Physicians may choose lower doses that avoid the side effects associated with the higher doses needed for significant weight loss, potentially also lowering costs for patients, Drucker suggested adding “We’re not saying weight loss isn’t important because many things improve when patients lose weight. But we now know that weight shouldn’t be the only measure of success, because GLP-1 medicines will improve liver health whether or not the patient loses weight.”
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
Want to understand the current state of AI? Check out these charts.
If you’re following AI news, you’re probably getting whiplash. AI is a gold rush. AI is a bubble. AI is taking your job. AI can’t even read a clock. Stanford’s 2026 AI Index—the field’s annual report card—cuts through the noise.
Stanford’s 2026 AI Index is full of striking stats. It also reveals a field riddled with inconsistencies, most notably in the gap between experts and non-experts.
On jobs, 73% of US experts view AI’s impact positively, compared to just 23% of the public. Similar divides emerged on the economy and healthcare. What’s driving this disconnect?
Part of the answer may lie in their diverging experiences. Those using AI for coding and technical work see it at its best, while everyone else gets a more mixed bag. The result is two very different realities. Read the full story on what they are—and why they matter.
This story is from The Algorithm, our weekly newsletter on AI. Sign up to receive it in your inbox every Monday.
—Will Douglas Heaven
Job titles of the future: Wildlife first responder
Grizzly bears have made such a comeback across eastern Montana that in 2017, the state hired its first-ever prairie-based grizzly manager: wildlife biologist Wesley Sarmento.
For seven years, Sarmento worked to keep both bears and humans out of trouble. He acted like a first responder, trying to defuse potentially dangerous situations. He even got caught in some himself, which led him to a new wildlife safety tool: drones. Find out the results of his experiments in digital ecology.
—Emily Senkosky
This article is from the next issue of our print magazine, which is all about nature. Subscribe now to read it when it lands on Wednesday, April 22.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Human scientists still trounce the top AI agents at complex tasks The best agents perform only half as well as experts with PhDs.(Nature) + Can AI really help us discover new materials? (MIT Technology Review)
2 OpenAI is escalating its fight with Anthropic while pulling away from Microsoft A leaked memo exposes plans to attack Anthropic. (Axios) + And says Microsoft “limited our ability” to reach clients. (The Information $) + While touting a budding alliance with Amazon. (CNBC)
3 Carbon removal technology is stalling—and that may be good news Better solutions could now emerge.(New Scientist) + Here are three that are set to break through. (MIT Technology Review)
4 AI is finding bugs faster than we can fix them—and hackers will benefit Welcome to the bug armageddon. (WSJ $) + AI may soon be capable of fully automated attacks. (MIT Technology Review)
5 A Texas man has been charged with the attempted murder of Sam Altman He allegedly threw a Molotov cocktail at the OpenAI CEO’s home last Friday. (NPR) + The suspect reportedly had a list of other AI leaders. (NYT $)
6 AI is beginning to transform mathematics It’s proving new results at a rapid pace. (Quanta) + One AI startup plans to unearth new mathematical patterns. (MIT Technology Review)
7 Students are turning away from computer science It’s had a massive drop in enrollments. (WP $) + AI coding tools have diminished the degree’s value. (NYT $)
8 India’s bid to become a data center hub is sparking a fierce backlash Farmers are protesting Delhi’s courtship of hyperscalers. (Rest of World)
9 Meta is set to overtake Google in advertising revenue this year And become the world’s largest digital ad platform for the first time. (WSJ)
10 AI influencers are taking over Coachella Synthetic content creators are “everywhere” at the festival. (The Verge)
Quote of the day
“These people are almost nothing like you. They are most likely sociopathic/psychopathic and, in the case of Altman, consistently reported to be a pathological liar.”
—The alleged firebomber of Sam Altman’s home shares his distrust of AI leaders in a blog post.
One More Thing
We’ve never understood how hunger works. That might be about to change.
A few years ago, Brad Lowell, a Harvard University neuroscientist, figured out how to crank the food drive to the maximum. He did it by stimulating neurons in mice. Now, he’s following known parts of the neural hunger circuits into uncharted parts of the brain.
The work could have important implications for public health. More than 1.9 billion adults worldwide are overweight, and more than 650 million are obese. Understanding the circuits involved could shed new light on why these numbers are skyrocketing.
BackgroundThe triglyceride-glucose (TyG) index and C-reactive protein-triglyceride-glucose index (CTI) are innovative indicators for assessing insulin resistance (IR) and inflammation, yet research on them in patients with schizophrenia remains limited. This study aimed to explore TyG index and CTI levels and their associations with psychopathology and brain-derived neurotrophic factor (BDNF) in patients with chronic schizophrenia (CS).MethodsThis cross-sectional study was conducted across one general hospital and two psychiatric hospitals in Anhui Province, China. Socio-demographic information and hematological parameters were collected from participants, and their psychiatric and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS), respectively.ResultsA total of 324 patients with CS and 150 healthy controls (HCs) were enrolled in the study. Compared with HCs, patients had higher TyG index and CTI levels (all P < 0.001). Binary logistic regression analyses revealed that among patients, a high TyG index level was significantly associated with higher BDNF levels and lower negative factor scores of the PANSS, while a high CTI level was significantly associated with higher depression-hopelessness factor scores of the CDSS and lower negative factor scores of the PANSS (all P < 0.05).ConclusionPatients with CS had higher levels of TyG index and CTI, which were significantly associated with the severity of negative and depressive symptoms, as well as BDNF levels. It is suggested that the integration of the TyG index and CTI into clinical monitoring for patients with CS is necessary.
A study of middle-aged adults carried out by researchers at Dokuz Eylul University in Turkey shows that health and metabolic profiles differ between men and women with obesity.
The results, which will be presented at the European Congress on Obesity in Istanbul in May, show men with obesity are more likely to develop abdominal fat and have high levels of liver enzymes and triglycerides in the blood than women.
In contrast, women with obesity had higher levels of total and low-density lipoprotein cholesterol and increased inflammatory markers such as C-reactive protein compared with men.
“Our findings reveal intriguing differences in the way men and women respond to obesity,” said presenting author Zeynep Pekel, from Dokuz Eylul University, Izmir, Turkey, in a press statement.
“They show just how important gender-specific research is. Not only are sex differences a powerful player in the pathology and course of obesity, but our results indicate that such differences could be a stepping stone toward finding targeted, sex-based therapies to help in the management of people living with obesity.”
Although it is known that men and women with obesity have different adipose tissue distribution and have differences in metabolism more generally, this knowledge is not widely applied in obesity care.
In this study, Pekel and colleagues carried out an analysis of 1134 adults living with obesity attending a tertiary obesity clinic, including 886 women and 248 men. They measured standard factors like age, body mass index (BMI), waist and hip circumference and blood pressure as well as blood-based biomarkers like lipids, liver enzymes and inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, and white blood cell count.
The results showed that women were slightly older at 45 years on average. Men had significantly greater waist circumference and systolic blood pressure than women, as well as higher levels of the liver enzymes alanine aminotransferase and gamma‑glutamyl transferase and the kidney health biomarker creatinine. Men also had higher levels of triglycerides than women in the study.
Women with obesity had significantly higher total and low-density lipoprotein cholesterol than men in the study. They also had greater erythrocyte sedimentation rate, C-reactive protein, and platelet count, than the men.
“It’s still early days and these findings need to be confirmed in other patient groups, but they offer important insight into how obesity may affect men and women differently,” said Pekel.
“These differences are likely influenced by biological factors such as hormones, immune responses, and fat distribution. Our next steps are to validate these findings in larger populations, better understand the biological processes behind these differences, and explore how these patterns relate to clinical risk.”
Background: Physical inactivity remains a public health concern, with 42% (around 1 in 2) of women and 34% (around 1 in 3) of men in the United Kingdom, for example, failing to meet moderate-to-vigorous physical activity guidelines. To promote physical activity (PA) at scale, smartphone-based mHealth (mobile health) software apps offer a promising solution. Objective: This study aims to evaluate the feasibility of implementing an mHealth app offering very small (“micro”) financial incentives for PA in Leeds, United Kingdom. Methods: A 5-week single-arm proof-of-concept study was conducted with rolling recruitment among Caterpillar Health app users between September 12 and December 12, 2022 (Obesity-Related Behavioral Intervention Trial model, phase IIa). Users earned microincentives in the form of “points,” redeemable for consumer rewards (eg, movie tickets and gym passes), for meeting personalized daily step goals (US $0.13 per goal achieved; set using data from a 5-day baseline) and completing educational quizzes (US $0.33 per quiz). Descriptive statistics assessed feasibility outcomes (ie, reach, recruitment, retention, engagement, and acceptability) and preliminary effectiveness. Paired-samples tests (<.05) examined changes in weekly mean daily step count (from baseline) and step goal achievement over 5 weeks. Results: Of 285 app downloads, 46 users consented to participate (recruitment rate: 16.1%). Participants (mean age: 39.9, SD 11.1 y; 71.1%, 33/46 woman) had a baseline step count of 5598 (SD 2664) steps/day. A total of 25 participants remained engaged (ie, completed at least 1 quiz) at study week 5 (retention rate: 54.3%). Acceptability was high, with 75% of respondents (12/16) indicating they would recommend the app. Weekly mean daily step count did not significantly increase from baseline (mean difference 317, SD 2273, =.53). Weekly daily step goal achievement rate (%) decreased from study week 1 to 5 (−23.23, SD 22.85, =.02). Conclusions: Despite lower-than-expected recruitment and no statistically significant PA increase, relatively high engagement and acceptability suggest future pilot testing (Obesity-Related Behavioral Intervention Trial model, phase IIb) of a refined intervention (eg, wider selection of loyalty reward partners) and modified study protocol (eg, simplified consent process) is warranted. Trial Registration: ClinicalTrials.gov NCT05294692; https://clinicaltrials.gov/study/NCT05294692
From designing drugs with a simple text prompt to running experiments guided by extended reality, a new wave of agentic AI is transforming the modern lab. Our editors discuss the latest autonomous systems accelerating biological discovery. In business deals, Gilead Sciences has acquired Tubulis in a transaction worth up to $5 billion, strengthening the buyer’s position in antibody–drug conjugates for cancer. Correspondingly, Eli Lilly and Biogen are each making billion-dollar-plus bets, acquiring Centessa, a sleep disorder drug developer, and Apellis, known for its work in immunology and rare diseases. Our episode rounds out by unpacking the dynamic obesity drug market, where intensifying competition from Novo Nordisk’s Wegovy pill is prompting Lilly to temper the 2026 sales outlook for its oral obesity drug, Foundayo.
Listed below are links to the GEN stories referenced in this episode of Touching Base:
Glucagon-like peptide-1 (GLP-1) therapies are under investigation for a growing number of neuropsychiatric conditions, including substance use disorders. Cigarette smoking accounts for the largest proportion of substance use-related morbidity and mortality, in part reflecting increased risk for cardiometabolic disease among people who smoke. Given modest quit rates with approved smoking cessation therapies, medications with novel mechanisms of action are needed to expand the available monotherapy and combination treatment options.
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.”
![A pioneer in GLP-1 biology Dr. Daniel Drucker has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today's widely popular medications for type 2 diabetes and obesity. Dr. Drucker's ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_Drucker_LTRI_Colin_Dewar-225x300.jpeg)
