Chia seeds show promise in supporting heart health, metabolic function

Chia seeds: A superfood for cardiometabolic health

Chia seeds, long a dietary staple in Mesoamerican cultures dating back to the Aztecs and Mayans, have attracted modern scientific scrutiny for their unusually dense nutritional profile. A 28-gram (g) serving—approximately two tablespoons—contains 138 calories, 8.7 g of fat, 11.9 g of carbohydrates, 9.7 g of fiber and 4.7 g of complete protein, according to data from the U.S. Department of Agriculture. Chia seeds also provide significant amounts of calcium, magnesium, iron and potassium.

Heart benefits

The most compelling evidence for chia seeds' cardiovascular benefits comes from studies examining their effect on blood pressure. In a study published in the journal Plant Foods for Human Nutrition, participants who consumed 35 grams of chia flour daily for 12 weeks experienced reduced blood pressure, even among those already taking antihypertensive medication. Researchers noted this effect occurred alongside reductions in inflammatory markers, including C-reactive protein, and improvements in clotting protein profiles.

Additional research has focused on chia seeds' potential to improve cholesterol levels. A meta-analysis of 10 clinical trials reported that regular consumption of chia seeds can reduce total cholesterol, triglycerides and LDL cholesterol while increasing HDL, suggesting a positive effect on lipid profile.

The seeds' high omega-3 fatty acid content appears central to these effects. Chia seeds contain alpha-linolenic acid, a plant-based omega-3 that the human body cannot produce independently. This fatty acid supports heart health, brain function and systemic anti-inflammatory activity. Chia seeds also contain multiple antioxidant compounds, including chlorogenic acid, caffeic acid, myricetin, quercetin and kaempferol, which may protect against oxidative damage linked to heart disease, cancer and aging.

Blood sugar control

For those managing Type 2 diabetes, chia seeds may offer particular value. Studies suggest that daily consumption of chia seeds—either 7-24 g incorporated into white bread or 34 g of whole-grain chia—reduces post-meal blood sugar levels as well as blood pressure in healthy individuals and diabetics alike. As explained by BrightU.AI's Enoch engine, chia seeds help lower blood sugar because their soluble fiber slows the absorption of sugar into the bloodstream, which prevents sharp spikes in glucose levels. This stabilizing effect is especially beneficial for managing diabetes and maintaining steady energy.

Animal studies report similar effects on diabetic rat models fed with chia seeds, suggesting that the seeds not only help with blood sugar control but may also help reduce cardiovascular risk factors in people with Type 2 diabetes.

How to safely incorporate chia seeds into your diet

Despite these promising findings, medical professionals emphasize that chia seeds are not without potential risks. Chia seeds' high oxalate content may increase kidney stone risk in susceptible individuals. Additionally, because chia seeds can lower both blood pressure and blood sugar, they may interact additively with prescription medications for hypertension and diabetes, potentially causing excessive reductions.

Gastrointestinal side effects remain the most common complaint. Chia seeds' high fiber content—nearly 10 grams per serving—can cause bloating, cramping and gas when introduced too quickly to the diet. Experts recommend gradually increasing fiber intake to allow the digestive system to adjust, and always consuming chia seeds with adequate water to prevent bowel obstruction.

The growing body of evidence supporting chia seeds' health benefits coincides with increasing consumer interest in functional foods. Chia seeds can be incorporated into diets through multiple methods: sprinkled on yogurt, salads or cereal; blended into smoothies; used as a thickener for soups and sauces; or soaked in water to form a gel that can substitute for eggs in baking. Ground chia seeds can be added to pancake batter or mixed into hummus and other dips.

Chia seeds represent one of several plant-based foods being studied for their potential to support cardiovascular health through accessible, affordable dietary changes rather than pharmaceutical interventions alone. The seeds join other functional foods, such as oats, flaxseed and fatty fish, in a growing list of whole foods associated with reduced cardiovascular and metabolic risks.

https://en.wikipedia.org/wiki/Chia_seed

Ensitrelvir cuts household COVID-19 risk when given after exposure

Ensitrelvir COVID-19 Prevention Background

The coronavirus disease 2019 (COVID-19) pandemic caused millions of deaths worldwide. Although its acute phase has waned, it continues to cause illness and death, especially in high-risk groups. This is partly due to its high mutation rate, waning immunity, and high household transmission rates of 32%-48%.

Since the use of masks and social distancing measures is not enough to completely prevent transmission, there is a need for effective preventive drugs, at least for those at increased risk. Earlier trials of nirmatrelvir-ritonavir and molnupiravir did not show significant protection against COVID-19 in exposed household contacts.

Ensitrelvir showed potent in vitro activity against multiple SARS-CoV-2 variants, including omicron. It is approved in Japan for the treatment of mild-to-moderate COVID-19 in patients aged 12 years or older. Currently, it has been approved in Japan for post-exposure prophylaxis in contacts aged 12 years or older, based on the findings of this study.

In the phase 3 SCORPIO-SR trial, it reduced COVID-19 symptoms when initiated within 72 hours of symptom onset. The phase 3 SCORPIO-HR trial demonstrated the drug's antiviral efficacy but failed to show a significant difference in time to symptom resolution.

This motivated the current phase 3 SCORPIO-PEP trial. It was conducted as a double-blind randomized controlled trial involving 2387 randomized household contacts, of whom 2041 were included in the modified intention-to-treat population. The mean age of the population was 42.4 years.

SCORPIO-PEP Trial Study Design

At baseline, all participants had a history of contact with someone with COVID-19, the index patient. All had nasopharyngeal swabs submitted on days 1, 3, 6, 10, 15, 21, and 28 for reverse transcriptase-polymerase chain reaction (RT-PCR) detection of SARS-CoV-2.

Those who were test-negative and asymptomatic at baseline were randomly assigned to receive either ensitrelvir (1,030 participants) or placebo (1,011 participants) for 5 days beginning within 72 hours after symptom onset in the index patient. The primary endpoint was symptomatic RT-PCR-confirmed COVID-19 by day 10.

This required symptomatic RT-PCR positivity within ten days of trial-drug or placebo administration. This included the appearance of one or more symptoms from a panel of 14, lasting at least 48 hours, or worsening in the case of preexisting symptoms.

Approximately 71% of participants were randomized within 48 hours of the index patient's onset of symptoms. About 37% had one or more risk factors for severe COVID-19, including obesity, smoking, and age above 65 years. Nearly 19% of index patients received antiviral therapy, mostly with ensitrelvir. Approximately 85% or more of those in each group completed the regimen.

Over 98% had antibodies to the SARS-CoV-2 nucleocapsid or spike antigens.

COVID-19 Prevention Efficacy Findings

Compared with the ensitrelvir group, the placebo group had a significantly higher rate of new COVID-19 cases (9% vs. 2.9%). The risk ratio in favor of the ensitrelvir group was 0.33, indicating a 67% reduction in relative risk in ensitrelvir recipients post-exposure, compared to placebo.

The observed reduction appears larger than reported in previous household contact PEP studies. However, comparisons of efficacy across trials should be interpreted cautiously in light of differences between trials, definitions of illness, and shorter time limits for delineating primary infection rates. Notably, these differences persisted even when adjusting for differences in the definition of COVID-19.

By day 2, the placebo group showed a rapid rise in symptomatic infections, which was both smaller and spread out over 12 days in the ensitrelvir group. The benefit appeared to be generally consistent across participants with and without risk factors, although subgroup analyses were not adjusted for multiplicity. Across the participating countries, COVID-19 incidence among household contacts was lower in the US than in Japan.

In this study, the drug maintained plasma concentrations above the estimated target concentration, compared to estimates derived from nonclinical studies. This might indicate the persistence of effective prophylaxis beyond the five-day regimen.

Viral Load and Safety Findings

RT-PCR-confirmed SARS-CoV-2 infection rates were also lower with ensitrelvir than with placebo. Among participants with baseline-positive RT-PCR, viral loads were lower, as were those among those who developed infection or symptomatic COVID-19 while on ensitrelvir.

Adverse events were similar in both groups, and neither group reported hospitalizations or deaths from COVID-19. Ensitrelvir was associated with reversible reductions in HDL cholesterol, and its use requires attention to potential drug-drug interactions because it is a moderately strong CYP3A inhibitor.

The researchers did not have data on other measures used to limit household transmission or on the difference in outcomes due to antiviral administration, which is common in Japan and was offered to 38% of patients versus 6% in the US. The risk of selecting for viral mutations associated with resistance following ensitrelvir administration could not be completely excluded due to missing viral sample data from index patients treated with ensitrelvir. Participants using contraindicated medications were also excluded, which may limit real-world generalizability in patients at risk of CYP3A-mediated drug interactions.

Ensitrelvir Post-Exposure Prophylaxis Implications

The findings suggest that when administered within 72 hours of symptom onset in a COVID-19 index patient, ensitrelvir effectively prevented symptomatic illness in household contacts and reduced the relative risk of the illness up to day 10 by 67% among participants who received at least one dose of the drug. Among high-risk participants, about 2.4% of those who received ensitrelvir developed COVID-19, compared with 10% in the placebo group.

https://en.wikipedia.org/wiki/Ensitrelvir

Ensitrelvir cuts household COVID-19 risk when given after exposure

Merck Scientists Publish Landmark Paper on Novel Method for Large-Scale Biocatalytic Synthesis of Investigational Oral PCSK9 Inhibitor, Enlicitide Decanoate

Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced the publication of work describing the large-scale synthesis of enlicitide decanoate, the company’s investigational oral PCSK9 inhibitor, using a tailored suite of enzymes in the latest issue of the peer reviewed journal Science.

• Publication in Science magazine outlines blueprint for the scalable
•  synthesis of complex orally available macrocyclic peptides
• Enlicitide, a novel macrocyclic peptide, has the potential to be the first approved oral PCSK9 inhibitor

“Macrocyclic peptides have the potential to unlock new opportunities to develop oral treatment options for challenging therapeutic targets and broaden patient access,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “The scalable production process for enlicitide described in this publication showcases Merck’s scientific capabilities and underscores our sustained commitment to helping address the global cardiovascular epidemic.”

In this publication, Merck scientists detail the biocatalytic assembly of enlicitide using a suite of enzymes that catalyze selective peptide fragment formation, coupling, and macrocyclization. Together with efficient purifications using crystallization, this strategy enabled the manufacture of a product that would not be possible with traditional synthetic methods. The method described offers a sustainable blueprint for the scalable development of complex macrocyclic peptide therapeutics, environmental advantages and manufacturing efficiencies that support efforts to expand patient access.

About biocatalysis

Biocatalysis describes the process of using enzymes to conduct chemical synthesis. Biocatalysis offers environmental sustainability advantages over chemical catalyst methods. For more than 25 years Merck has invested in the development of biocatalysis including the generation of novel enzymes for the synthesis and novel manufacturing of pharmaceutical products at scale.

About macrocyclic peptides

Over a decade ago, an interdisciplinary team of Merck scientists were challenged to create a type of medicine that may provide the potency and selectivity of a biologic therapy but in the form of a pill. Macrocyclic peptides are intricate ring-shaped molecules with the ability to target and disrupt protein-protein interactions while retaining oral bioavailability. For more information regarding our approach to macrocyclic peptides, visit merck.com

About enlicitide and PCSK9

Enlicitide has the potential to be the first approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

About the CV epidemic and atherosclerotic cardiovascular disease

The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

https://en.wikipedia.org/wiki/Enlicitide_decanoate

Merck Scientists Publish Landmark Paper on Novel Method for Large-Scale Biocatalytic Synthesis of Investigational Oral PCSK9 Inhibitor, Enlicitide Decanoate 

Daily orforglipron treatment reduces weight and blood sugar in seniors

In continuation of my update on orforglipron

A new analysis to be presented at this year's European Congress on Obesity (ECO 2026, Istanbul, Turkey, 12-15 May) examined daily oral orforglipron treatment for the treatment of obesity, with or without diabetes, in users aged 65 years and over, with results and a safety profile similar to that seen in the ATTAIN clinical trial programme population. Lead author for this post-hoc analysis is Dr Deborah Horn, Director of the Center for Obesity Medicine and Metabolic Performance at McGovern Medical School at UTHealth Houston, Houston, Texas, USA, and colleagues.

Limited clinical data exist on the use of incretin-based obesity management medications in older adults with or without type 2 diabetes (T2D), and a lack of specific analyses related to older users could be a factor that could make providers or patients in this age group hesitant when considering therapy choices.

Orforglipron is a novel small-molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed by Eli-Lilly and Company (Lilly), who sponsored these analyses. The drug was approved by the US Food and Drug Administration for chronic weight management on April 1, 2026.

Orforglipron demonstrated significant weight reduction vs. placebo in the phase 3, randomised, double-blind, multinational ATTAIN-1 and ATTAIN-2 clinical trials in participants with obesity or obesity and T2D, respectively. In this new analysis of those trials, the authors evaluated efficacy and safety of orforglipron versus placebo in a sub-group of participants aged 65 years and older from ATTAIN-1 and ATTAIN-2.

The ATTAIN-1 and ATTAIN-2 global clinical trials evaluated once-daily orforglipron 6 mg, 12 mg, or 36 mg vs. placebo as an adjunct to healthy diet and physical activity in participants from 9 and 10 countries, respectively. In this sub-group analysis, efficacy outcomes were analysed separately for each trial, and safety data were pooled. The primary endpoint was percent change in body weight from baseline to week 72.

In ATTAIN-1 and ATTAIN-2, 616 randomised participants were ≥65 years of age (n=196 and 420, respectively). Of those, 613 received treatment (orforglipron 6 mg, n=118; 12 mg, n=135; 36 mg, n=146; placebo, n=214). And 79.1% of ATTAIN-1 and 86.2% of ATTAIN-2 participants had hypertension as a comorbidity.

At Week 72, the percent change in weight from baseline in users aged 65 and over in ATTAIN-1 (participants with obesity and without T2D) was –7.9%, –11.3%, and –13.0% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, vs. –1.6% with placebo, all statistically significant findings. Similar results were found for those users aged 65 years and over with T2D and obesity in ATTAIN-2: orforglipron 6 mg: –7.5%; 12 mg: –8.3%; 36 mg: –12.2%; placebo: –2.3% again with all results statistically significant.

Participants with T2D experienced reductions from baseline in glycated haemoglobin (HbA1c – a measure of blood sugar control) of –1.5%, –1.6%, and –1.7% with 6 mg, 12 mg, and 36 mg orforglipron, respectively, vs. –0.1% with placebo. BMI, waist circumference, triglycerides, non-HDL cholesterol, and health-related quality of life also improved in orforglipron vs. placebo treatment groups in participants with or without T2D. 

https://en.wikipedia.org/wiki/Orforglipron

Daily orforglipron treatment reduces weight and blood sugar in seniors

Semaglutide shows sustained weight loss benefits in older adults

In continuation of my update on semaglutide

A new analysis of the STEP trails carried out by semaglutide manufacturer Novo Nordisk has analysed various trials to show the safety and efficacy of the obesity drug semaglutide in older adults (over 65 years), and found similar efficacy and safety as in the general trial populations . The study is by Prof Luca Busetto from the University of Padova in Italy and colleagues including from Novo Nordisk, who sponsor this new study.

Individuals of advanced age with obesity represent a vulnerable group, often presenting with comorbidities and frailty, and being at risk of adverse events (AEs). Information on the use of glucagon-like peptide-1 (GLP-1) receptor agonists including semaglutide in this population is limited; therefore, the authors decided assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg in individuals aged 65 years and over.

The analysis pooled together data from the STEP 1, 3, 4, 5, 8 and 9 trials (only in people with obesity or overweight, not diabetes, because weight loss in obesity drug trials is always lower in people with diabetes than without – thus results cannot be compared or mixed). It included participants aged ≥65 years with body mass index of at least 30 kg/m², or at least 27 kg/m² and at least 1 obesity-related complication (without diabetes) who were randomised to receive semaglutide 2.4 mg or placebo. All participants received lifestyle intervention and, in STEP 3, intensive behavioural therapy. Endpoints were assessed from baseline to week 68 and included percentage change in body weight; proportion of participants achieving categorical body weight reductions (≥10%, ≥15%, ≥20%); change in waist circumference; proportion of participants achieving waist to height ratio (WHtR) <0.53; shift in BMI category; and changes in cardiometabolic risk factors (glucose parameters, blood pressure, serum lipids and hs-CRP). Adverse events (AEs) were also assessed.

Of the total population in the selected trials (N=4523), 358 participants (8%) were aged 65 years or older and included in the analysis (semaglutide 2.4 mg, n=248; placebo, n=110), with most (90%) being aged 65–74 years (and the others 75 years and over). Across the pooled semaglutide and placebo groups at baseline, mean age was 69 years, bodyweight was 99.0 kg, BMI was 36.6 kg/m² and waist circumference was 115 cm; 72% were female.

At week 68, there was a mean −15.4% change in body weight for semaglutide 2.4 mg vs −5.1% for placebo, and a mean −14.3 cm vs −6.0 cm change in waist circumference, respectively. Proportions of participants achieving body weight reduction thresholds in the semaglutide 2.4 mg vs placebo groups were 66.5% vs 15.5% (at least 10%), 46.8% vs 6.4% (at least 15%) and 28.6% vs 2.7% (at least 20%), respectively.

In the semaglutide 2.4 mg group, 11.3% achieved a WHtR <0.53, compared with 4.5% with placebo. A greater proportion of semaglutide-treated participants improved their BMI category from baseline to week 68 compared with placebo (see Figure full abstract). A BMI of <27 kg/m² (so called healthy weight) was achieved by 27.0% of participants in the semaglutide group vs 5.5% in the placebo group; and the proportion of elderly patients in the overweight and obesity class I, II and III categories all fell in the semaglutide group at week 68 due to the increase in participants who had reached a healthy weight.

For participants achieving both a BMI of 27 or less and a WHtR of <0.53 these values were 10.5% vs 2.7%, respectively. Greater improvements in cardiometabolic risk factors were observed with semaglutide 2.4 mg vs placebo (see Table full abstract), including blood pressure, blood fats, cholesterol and glycated haemoglobin (HbA1c – a measure of blood sugar control used in diagnosis of diabetes).

Proportions of participants experiencing AEs and serious AEs in the semaglutide 2.4 mg vs placebo groups were similar for AEs overall (89.1% vs 84.5%), but higher for semaglutide re: serious AEs - 19.0% vs 12.7%, respectively. Constipation and dizziness rates (known side effects of this class of drug) were higher with semaglutide, while fractures and hypoglycaemia were comparable to placebo, both affecting less than 1% in each group.

https://en.wikipedia.org/wiki/Semaglutide

Semaglutide shows sustained weight loss benefits in older adults

How statins harm muscles—and how to stop it

In continuation of my update  on statin 

Statins have transformed heart health, saving millions of lives by lowering cholesterol and reducing the risk of heart attacks and strokes. But for many patients, these drugs come with a troubling downside: muscle pain, weakness and, in rare cases, severe muscle breakdown that can lead to kidney failure.

University of British Columbia researchers and their collaborators at the University of Wisconsin-Madison have now pinpointed the cause. Their findings, published last week in Nature Communications, could pave the way for a new generation of statins without these side effects.

How statins affect muscle cells

The team used cryo-electron microscopy, a powerful imaging technique that reveals proteins at near-atomic detail, to capture how statins interact with a critical muscle protein called the ryanodine receptor (RyR1). This protein acts like a gatekeeper for calcium inside muscle cells, opening only when muscles need to contract. When statins bind to it, they force the gate open, causing calcium to leak continuously—a toxic effect that can damage muscle tissue.

"We were able to see, almost atom by atom, how statins latch onto this channel," said lead author Dr. Steven Molinarolo, a postdoctoral researcher in UBC's department of biochemistry and molecular biology. "That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications."

Implications for future statin development

The study focused on atorvastatin, one of the most widely prescribed statins, but the findings suggest the effect may be common across the drug class. The researchers discovered that statins bind in a highly unusual way: Three molecules cluster together inside a pocket of the protein. The first molecule attaches when the channel is closed, priming it to open. Two more molecules then wedge in, forcing the channel wide open.

"This is the first time we've had a clear picture of how statins activate this channel," said Dr. Filip Van Petegem, senior author and professor at UBC's Life Sciences Institute. "It's a big step forward because it gives us a roadmap for designing statins that don't interact with muscle tissue."

By adjusting only those parts of the statin molecule that are responsible for the negative effects, scientists could preserve the part that lowers cholesterol while reducing the risk.

https://en.wikipedia.org/wiki/Statin

How statins harm muscles—and how to stop it

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

In continuation of my update on Polyphenol-rich diets

 People who regularly consume polyphenol-rich foods and drinks, such as tea, coffee, berries, cocoa, nuts, whole grains and olive oil, may have better long-term heart health

The research, led by King's College London, found that those with higher adherence to polyphenol-rich dietary patterns had lower predicted cardiovascular disease (CVD) risk.

Polyphenols are natural compounds found in plants that are linked to various health benefits, including improved heart, brain, and gut health.

The study, published today in BMC Medicine, followed more than 3,100 adults from the TwinsUK cohort for over a decade, found that diets rich in specific groups of polyphenols were linked to healthier blood pressure and cholesterol profiles, contributing to lower CVD risk scores.

For the first time, the researchers also analyzed a large number of metabolites in the urine that are produced when the body breaks down polyphenols.

These biomarkers confirmed that individuals with higher levels of polyphenol metabolites—especially those derived from specific groups of polyphenols, flavonoids and phenolic acids—had lower cardiovascular risk scores. They also had increased HDL cholesterol, also know as "good" cholesterol.

The study used a newly developed polyphenol dietary score (PPS) to capture intake of 20 key polyphenol-rich foods commonly consumed in the U.K., ranging from tea and coffee to berries, olive oil, nuts, and whole grains.

This score showed stronger associations with cardiovascular health than estimates of total polyphenol intake, likely because it captures overall dietary patterns rather than individual compounds. This finding suggests that considering the whole diet provides a more accurate picture of how polyphenol-rich foods work together to support long-term heart health

Professor Ana Rodriguez-Mateos, senior author and Professor of Human Nutrition at King's College London, said, "Our findings show that long-term adherence to polyphenol-rich diets can substantially slow the rise in cardiovascular risk as people age. Even small, sustained shifts towards foods like berries, tea, coffee, nuts, and whole grains may help protect the heart over time."

Dr. Yong Li, first author of the study, added, "This research provides strong evidence that regularly including polyphenol-rich foods in your diet is a simple and effective way to support heart health. These plant compounds are widely available in everyday foods, making this a practical strategy for most people."

The researchers note that while cardiovascular risk naturally increases with age, higher polyphenol intake was associated with a slower progression of risk over the 11-year follow-up period. They also emphasize the need for future dietary intervention studies to further validate these associations.

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

People who regularly consume polyphenol-rich foods and drinks, such as tea, coffee, berries, cocoa, nuts, whole grains and olive oil, may have better long-term heart health.

The research, led by King's College London, found that those with higher adherence to polyphenol-rich dietary patterns had lower predicted cardiovascular disease (CVD) risk.

Polyphenols are natural compounds found in plants that are linked to various health benefits, including improved heart, brain, and gut health.

The study, published today in BMC Medicine, followed more than 3,100 adults from the TwinsUK cohort for over a decade, found that diets rich in specific groups of polyphenols were linked to healthier blood pressure and cholesterol profiles, contributing to lower CVD risk scores.

For the first time, the researchers also analyzed a large number of metabolites in the urine that are produced when the body breaks down polyphenols.

These biomarkers confirmed that individuals with higher levels of polyphenol metabolites—especially those derived from specific groups of polyphenols, flavonoids and phenolic acids—had lower cardiovascular risk scores. They also had increased HDL cholesterol, also know as "good" cholesterol.

The study used a newly developed polyphenol dietary score (PPS) to capture intake of 20 key polyphenol-rich foods commonly consumed in the U.K., ranging from tea and coffee to berries, olive oil, nuts, and whole grains.

This score showed stronger associations with cardiovascular health than estimates of total polyphenol intake, likely because it captures overall dietary patterns rather than individual compounds. This finding suggests that considering the whole diet provides a more accurate picture of how polyphenol-rich foods work together to support long-term heart health.

Professor Ana Rodriguez-Mateos, senior author and Professor of Human Nutrition at King's College London, said, "Our findings show that long-term adherence to polyphenol-rich diets can substantially slow the rise in cardiovascular risk as people age. Even small, sustained shifts towards foods like berries, tea, coffee, nuts, and whole grains may help protect the heart over time."

Dr. Yong Li, first author of the study, added, "This research provides strong evidence that regularly including polyphenol-rich foods in your diet is a simple and effective way to support heart health. These plant compounds are widely available in everyday foods, making this a practical strategy for most people."

The researchers note that while cardiovascular risk naturally increases with age, higher polyphenol intake was associated with a slower progression of risk over the 11-year follow-up period. They also emphasize the need for future dietary intervention studies to further validate these associations.

https://link.springer.com/article/10.1186/s12916-025-04481-5

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

FDA Approves Foundayo (orforglipron), the Only GLP-1 Pill for Weight Loss That Can be Taken Any Time of Day Without Food or Water Restrictions

Eli Lilly and Company (NYSE: LLY)  announced the FDA approval of   Foundayo™ (orforglipron) for adults with obesity, or overweight with weight-related medical problems. When used alongside a reduced-calorie diet and increased physical activity, Foundayo helps individuals lose excess body weight and keep the weight off. Foundayo will be available via LillyDirect®, with prescriptions accepted immediately and shipping beginning April 6, followed shortly after by broad availability through U.S. retail pharmacies and telehealth providers.

Adults taking Foundayo lost an average of 27 pounds on the highest dose in the ATTAIN-1 clinical trial1

Foundayo, Lilly's second FDA-approved obesity medicine, will be available via LillyDirect® with free home delivery, starting at $25 per month with commercial coverage and $149 for self-pay

"People living with obesity need treatment options that meet them where they are – and for many, a once-daily pill that can be taken with no food or water restrictions can offer them greater flexibility in how they approach their treatment," said Deborah Horn, DO, director of the Center for Obesity Medicine at McGovern Medical School at UTHealth Houston. "With Foundayo, we now have an oral option that delivered an average of 12.4% weight loss at the highest dose in clinical trials – addressing both the clinical realities of obesity and the practical challenges patients face every day."

Supported by the rigorous ATTAIN clinical trial program, Foundayo was proven to help people lose weight and keep it off. In the ATTAIN-1 trial, individuals taking the highest dose of Foundayo and who stayed on treatment lost an average of 27.3 pounds (12.4%) compared to 2.2 pounds (0.9%) with placebo.1 Participants taking Foundayo, regardless of trial completion, lost an average of 25 pounds (11.1%), compared to 5.3 pounds (2.1%) with placebo.2 In the ATTAIN program, Foundayo also led to reductions in many markers of cardiovascular risk, including waist circumference, non-HDL cholesterol, triglycerides and systolic blood pressure across all doses.

"Today, fewer than 1 in 10 people who could benefit from a GLP-1 are taking one, held back by access, stigma, perceived complexity or the belief that their condition isn't serious enough for treatment. We believe Foundayo can help level the playing field for those living with obesity or who are overweight and living with weight-related complications," said David A. Ricks, chair and CEO of Eli Lilly and Company. "As a convenient, once-daily oral pill that delivers meaningful weight loss, this is obesity care designed for the real world."

Lilly is committed to making Foundayo accessible and affordable. Eligible people with commercial insurance may pay as little as $25 per month with the Foundayo savings card.3 Individuals opting for self-pay can access Foundayo starting at $149 per month for the lowest dose. Additionally, eligible Medicare Part D individuals may be able to get Foundayo for $50 per month, beginning as soon as July 1, 2026.

Use of Foundayo with other GLP-1 receptor agonist medicines is not recommended. It is not known whether Foundayo is safe and effective for use in children. Foundayo may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing or shortness of breath. If you have any of these symptoms, tell your health care provider. The most common side effects of Foundayo include nausea, constipation, diarrhea, vomiting, indigestion, stomach (abdominal) pain, headache, swollen belly, feeling tired, belching, heartburn, gas, and hair loss. These are not all the possible side effects of Foundayo.

"There is no single path that works for everyone living with overweight or obesity," said Joe Nadglowski, president and CEO of the Obesity Action Coalition. "New treatment options expand choice and help more people find care that fits their lives, their goals and where they are in their journey – whether they're just starting to explore treatment or looking for a different long-term approach."

Lilly has submitted orforglipron for weight management and/or type 2 diabetes in more than 40 countries and plans to launch in each country shortly after approval

https://en.wikipedia.org/wiki/Orforglipron

More: 

FDA Approves Foundayo (orforglipron), the Only GLP-1 Pill for Weight Loss That Can be Taken Any Time of Day Without Food or Water Restrictions

FDA Approves Inluriyo (imlunestrant) for Adults with ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

Eli Lilly and Company (NYSE: LLY) announced  the U.S. Food and Drug Administration (FDA)  approval of  Inluriyo (imlunestrant, 200 mg tablets), an oral estrogen receptor antagonist, for the treatment of adults with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–), ESR1-mutated advanced or metastatic breast cancer (MBC) whose disease progressed after at least one line of endocrine therapy (ET). In the Phase 3 EMBER-3 trial, Inluriyo reduced the risk of progression or death by 38% versus ET. Among patients with ESR1-mutated MBC, Inluriyo significantly improved progression-free survival (PFS) versus fulvestrant or exemestane, with a median PFS of 5.5 months vs 3.8 months (HR=0.62 [95% CI: 0.46-0.82]); p-value=0.0008.

Inluriyo is a treatment for ER+, HER2–, ESR1-mutated MBC. Some breast cancers develop ESR1 mutations that can cause estrogen receptors to become overactive and drive cancer growth. Inluriyo binds, blocks, and facilitates the degradation of these receptors, helping to slow disease progression. Its once-daily dosing provides patients with an oral treatment option.

"This therapy reflects our commitment to developing treatments that improve outcomes for people with breast cancer and represents an important step toward advancing innovative, all-oral treatment approaches," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "We are deeply grateful to the patients, investigators, Lilly team members and clinical care teams who made this advancement possible. This therapy has the potential to make the treatment journey more manageable for those living with breast cancer."

The Inluriyo label contains a warning and precaution for embryo-fetal toxicity.

The FDA approval is based on the results of the EMBER-3 trial in the patient population harboring ESR1-mutated MBC (n=256). Patients received Inluriyo or ET as first-line treatment for MBC following recurrence on adjuvant aromatase inhibitor (AI), +/- prior CDK4/6 inhibitor (21%), or as second-line treatment for MBC following progression on AI, +/- prior CDK4/6 inhibitor (79%).

"This represents an important advancement for patients with ESR1-mutated MBC, a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance," said Komal Jhaveri, M.D., FACP, FASCO, section head of Endocrine Therapy Research and clinical director of Early Drug Development at Memorial Sloan Kettering Cancer Center, and a principal investigator of EMBER-3. "With its demonstrated efficacy, tolerability profile and oral administration, this therapy provides a meaningful alternative treatment option for this patient population."

In EMBER-3, the majority of adverse events (AEs) with Inluriyo were low grade (Grade 1-2) and the most common adverse reactions (≥10%), including laboratory abnormalities, were hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain. In the study, 4.6% of patients permanently discontinued treatment due to AEs. Dose reductions and dose interruptions occurred in 2.4% and 10% of patients, respectively.

"The approval of Inluriyo expands the metastatic breast cancer treatment landscape for patients who test positive for the ESR1 mutation," said Jean Sachs, CEO, Living Beyond Breast Cancer. "Eligible patients will now have access to an additional treatment option, offering them the potential for flexibility in their daily lives and disease management, and—above all—renewed hope for the future."

Inluriyo is also being studied in the ongoing Phase 3 EMBER-4 trial in the adjuvant setting for people with ER+, HER2– early breast cancer (EBC) at increased risk of recurrence, which is enrolling approximately 8,000 patients worldwide.

https://en.wikipedia.org/wiki/Imlunestrant#:~:text=Society%20and%20culture-,Legal%20status,under%20the%20brand%20name%20Inluriyo.

FDA Approves Inluriyo (imlunestrant) for Adults with ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

FDA Grants Accelerated Approval for Rezdiffra (resmetirom) for the Treatment of Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH)

Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH),  announced the U.S. Food and Drug Administration (FDA)  accelerated approval for Rezdiffra (resmetirom) in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.

Bill Sibold, Chief Executive Officer of Madrigal, stated, “NASH with moderate to advanced liver fibrosis is a serious and progressive liver disease that, until now, has not had an FDA-approved therapy. The accelerated approval of Rezdiffra is a culmination of more than 15 years of research from our founder Dr. Becky Taub and a small R&D team that took on one of the biggest challenges in drug development. This is a historic moment for the NASH field and represents the best of what our industry is capable of. We’re excited to deliver Rezdiffra to patients in need.”

Becky Taub, M.D., the Founder, Chief Medical Officer and President of Research & Development of Madrigal, stated, “Madrigal would like to thank the many patients who made the accelerated approval of Rezdiffra possible by participating in our clinical studies. We believe Rezdiffra will change the treatment paradigm for NASH with moderate to advanced liver fibrosis, giving physicians a liver-directed therapy to help improve fibrosis and resolve NASH before their patients progress to cirrhosis.”

Wayne Eskridge, Co-Founder and Chief Executive Officer of the Fatty Liver Foundation, stated, “This is a day of celebration for patients with NASH who have been waiting many years for the first approved therapy. I believe this approval milestone will bring new energy and momentum to the NASH community, accelerating our efforts to improve disease education, build care pathways, and expand investment in NASH research.”

Rezdiffra is a once-daily, oral THR-β agonist designed to target key underlying causes of NASH. The accelerated approval of Rezdiffra was based on results from the Phase 3 MAESTRO-NASH trial, which was recently published in the New England Journal of Medicine. MAESTRO-NASH is an ongoing pivotal, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1,759 patients with biopsy-confirmed NASH. Following 52 weeks of treatment, both 100 mg and 80 mg doses of Rezdiffra demonstrated statistically significant improvement compared to placebo on two primary endpoints: NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points) with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. Fibrosis improvement and NASH resolution were consistent regardless of age, gender, type 2 diabetes status, or fibrosis stage.

The Rezdiffra prescribing information does not include a liver biopsy requirement for diagnosis. The recommended dosage of Rezdiffra is based on actual body weight. For patients weighing <100 kg (220 lbs.), the recommended dosage is 80 mg orally once daily. For patients weighing ≥100 kg (220 lbs.), the recommended dosage is 100 mg orally once daily.

Stephen Harrison, M.D., Chairman for both Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and lead Principal Investigator of the MAESTRO studies, commented, “The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition. Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis.”

Dr. Harrison continued, “Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality.”

MAESTRO-NASH remains ongoing as an outcomes study designed to generate confirmatory data that, if positive, will help verify clinical benefit and may support full approval. A second ongoing outcomes trial is evaluating progression to liver decompensation events in patients with well-compensated NASH cirrhosis treated with Rezdiffra versus placebo.

Rezdiffra should not be used in patients with decompensated cirrhosis. The most common adverse reactions reported in patients treated with Rezdiffra included diarrhea, nausea, pruritis, abdominal pain, vomiting, constipation, and dizziness. Diarrhea and nausea typically began early in treatment initiation and were mild to moderate in severity. A separate, noninvasive Phase 3 trial, MAESTRO-NAFLD-1, evaluated the safety and tolerability of Rezdiffra and contributed to the safety database supporting regulatory benefit-risk assessment.

Rezdiffra is expected to be available to patients in the U.S. in April and will be distributed through a limited specialty pharmacy network. Madrigal is committed to helping appropriate patients who may benefit from Rezdiffra access the medication through the Madrigal Patient Support program. This program is designed to help patients navigate insurance and affordability challenges and provide co-pay support for eligible patients. Madrigal has also established a patient assistance program (PAP) to help patients with no insurance access Rezdiffra.

Phase 3 MAESTRO-NASH Trial Results

MAESTRO-NASH is an ongoing Phase 3 trial that enrolled 1759 patients with biopsy-confirmed NASH. Patients were randomly assigned in a 1:1:1 ratio to receive once-daily Rezdiffra at a dose of 80 mg or 100 mg or placebo. The two primary endpoints at week 52 were NASH resolution with no worsening of fibrosis and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. The key secondary endpoint was the percent change from baseline in LDL cholesterol at week 24.

Rezdiffra achieved both primary endpoints and the key secondary endpoint of the MAESTRO-NASH trial. Additionally, Rezdiffra improved liver enzymes, fibrosis biomarkers and imaging tests as compared with placebo. The primary results of the trial were published in the New England Journal of Medicine in February 2024.

Patients enrolled in the MAESTRO-NASH trial continue on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy and hepatic decompensation events, as well as all-cause mortality. The 54-month outcomes portion of the trial is designed to generate confirmatory data that, if positive, will help verify Rezdiffra’s clinical benefit and may support full approval.

Ref: https://en.wikipedia.org/wiki/Resmetirom

FDA Grants Accelerated Approval for Rezdiffra (resmetirom) for the Treatment of Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH)

FDA Approves Zepbound (tirzepatide) for Chronic Weight Management

• 
• The U.S. Food and Drug Administration (FDA) approved Eli Lilly and Company's (NYSE: LLY) Zepbound™ (tirzepatide) injection, the first and only obesity treatment of its kind that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors. Zepbound is indicated for adults with obesity (with a BMI of 30 kg/m2 or greater), or those who are overweight (with a BMI of 27 kg/m2 or greater) and also have weight-related medical problems such as hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease, to lose weight and keep it off. It should be used with a reduced-calorie diet and increased physical activity. Zepbound should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines, and it has not been studied in patients with a history of pancreatitis, or with severe gastrointestinal disease, including severe gastroparesis.
• "Obesity is a chronic disease that can result in serious health complications, including heart disease, stroke and diabetes. Despite our knowledge of obesity as a treatable, chronic disease, people living with obesity still face many challenges in their health and weight management journey," said Joe Nadglowski, president and chief executive officer of the Obesity Action Coalition. "New treatment options bring hope to the many people with obesity who struggle with this disease and are seeking better options for weight management."
• The approval was based on results from the phase 3 SURMOUNT-1 and SURMOUNT-2 trials. In SURMOUNT-1, a study in 2,539 adults with obesity, or excess weight and weight-related medical problems not including diabetes, people taking Zepbound as an adjunct to diet and exercise experienced substantial weight loss compared with placebo at 72 weeks. At the highest dose (15 mg), people taking Zepbound lost on average 48 lb., while at the lowest dose (5 mg), people lost on average 34 lb. (compared to 7 lb. on placebo).
• Additionally, 1 in 3 patients taking Zepbound at the highest dose lost over 58 lb. (25% of body weight), compared to 1.5% on placebo, according to data not controlled for type 1 error. The average starting weight was 231 lb.
• While not approved to treat these conditions, in a clinical trial, people who dieted, exercised and took Zepbound for the treatment of obesity or overweight with weight-related medical problems observed changes in cholesterol and reductions in blood pressure and waist size.
• "Unfortunately, despite scientific evidence to the contrary, obesity is often seen as a lifestyle choice – something that people should manage themselves," said Dr. Leonard Glass, senior vice president global medical affairs, Lilly Diabetes and Obesity. "For decades, diet and exercise have been a go-to, but it's not uncommon for a person to have tried 20-30 times to lose weight with this approach. Research now shows that the body may respond to a calorie-deficit diet by increasing hunger and reducing feelings of fullness, making weight loss more difficult. Lilly is aiming to eliminate misperceptions about this disease and transform how it can be managed."
• Zepbound use may be associated with gastrointestinal adverse reactions, sometimes severe. The most commonly reported adverse events (observed in ≥ 5% of clinical trial participants) were nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection-site reactions, fatigue, hypersensitivity reactions, eructation, hair loss and gastroesophageal reflux disease.1 In studies, most nausea, diarrhea and vomiting occurred when people increased their dose – but the effects generally decreased over time. In studies, gastrointestinal side effects were more common in people taking Zepbound than people taking placebo, and people taking Zepbound were more likely than those on placebo to stop treatment because of these side effects. The label for Zepbound includes a Boxed Warning regarding thyroid C-cell tumors. Zepbound is contraindicated in patients with a personal or family history of medullary thyroid carcinoma, in patients with Multiple Endocrine Neoplasia syndrome type 2, and in patients with known serious hypersensitivity to tirzepatide or any of the excipients in Zepbound. See Important Safety Information below and full Prescribing Information and Medication Guide.
• "Far too many hurdles continue to prevent people living with obesity from accessing obesity treatments that could lead to significant weight loss," said Mike Mason, executive vice president and president, Lilly Diabetes and Obesity. "Broader access to these medicines is critical, which is why Lilly is committed to working with healthcare, government and industry partners to ensure people who may benefit from Zepbound can access it."
• Zepbound is expected to be available in the U.S. by the end of the year in six doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) at a list price of $1,059.87, which is approximately 20% lower than semaglutide 2.4 mg injection for weight loss. List price does not reflect the typical out-of-pocket cost to patients given insurance coverage and discounts. Lilly is putting a commercial savings card program in place that will help people who may benefit from Zepbound better access it.

• People who are commercially insured with coverage for Zepbound may be eligible to pay as low as $25 for a 1-month or 3-month prescription.
• People who are commercially insured without coverage for Zepbound may be eligible to pay as low as $550 for a 1-month prescription of Zepbound, approximately 50% lower than the list price.
• People may begin using the savings card program in the days following product availability at U.S. pharmacies. To learn more about these programs, or to sign up to receive the latest news, please visit www.Zepbound.lilly.com. Terms and conditions apply.
• Tirzepatide is also under regulatory review for weight management in Europe, China, the United Kingdom and several additional markets.

--------------------------------------------------------------------------------------------------------------------------

FDA Approves Zepbound (tirzepatide) for Chronic Weight Management

FDA Approves Leqvio (inclisiran), First-in-Class siRNA to Reduce Low-Density Lipoprotein Cholesterol (LDL-C)

                       In continuation of my update on inclisiran

                             Novartis today announced the US Food and Drug Administration (FDA) approval of Leqvio® (inclisiran), the first and only small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (also known as bad cholesterol or LDL-C) with two doses a year, after an initial dose and one at three months.

"Leqvio is a revolutionary approach to lower LDL-C, and creates new possibilities for how  healthcare systems can impact cardiovascular disease, a defining public health challenge of our time," said Vas Narasimhan, Novartis CEO. "We now have the opportunity, working together with partners, to provide this first-ever approved LDL-C–lowering siRNA-based therapy to tackle ASCVD at scale across the United States."

Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway.

"ASCVD is a substantial public health burden affecting 30 million Americans," said Norman Lepor, MD, a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio. "As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target."

Leqvio reduces the amount of LDL-C in the bloodstream by improving the liver's natural ability to prevent the production of a protein that plays a role in keeping circulating cholesterol levels high6,7. It is a subcutaneous injection given by a healthcare provider with an initial dose, then again at three months, and then every six months1. This approach may help those who have trouble sticking to medicines that are self-administered and have greater dosing frequency. Leqvio will be available in early January 2022.

"People with ASCVD have most likely experienced a heart attack or stroke from high cholesterol, causing a burden on the family and having a negative impact on lives," said Andrea Baer, Executive Director of The Mended Hearts, Inc. "One of the first steps to improving patients' health is to manage high cholesterol and we're encouraged that this new twice-a-year treatment offers a new option." 

The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, in which all 3,457 participants with ASCVD or HeFH had elevated LDL-C while receiving a maximally tolerated dose of statin therapy2,3. In the Phase III trials at month 17, Leqvio delivered effective and sustained LDL-C reduction of up to 52% vs. placebo and was reported to be well-tolerated with a safety profile shown to be comparable to placebo2,3. The most common side effects were mild to moderate injection site reaction (including pain, redness and rash), joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms and shortness of breath2,3.

Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

https://en.wikipedia.org/wiki/Inclisiran