Obesity Care Tag

Maternal Obesity Linked to Early Changes in Infant Gut Microbiome, Study Suggests

Key Takeaways: 

• Infants born to mothers with obesity show distinct differences in gut bacteria during the first six months of life, including reduced microbial diversity.
  
• These early microbial changes are associated with pathways linked to fat metabolism, particularly in the first three months after birth.
  
• Researchers suggest that early-life interventions targeting the gut microbiome may help reduce longer-term metabolic risks for children.
  
  

Maternal obesity and the infant gut microbiome

Babies born to mothers with obesity may begin life with a markedly different gut microbiome, a factor that could influence their metabolism and long-term health, according to new research from Nazarbayev University (NU).

The study, led by researchers Almagul Kushugulova and Samat Kozhakhmetov, explored how maternal obesity may shape the early development of the gut microbiome in infants. The research team followed 24 mothers and their babies from birth to six months of age, analysing stool samples using advanced DNA sequencing techniques.

By comparing infants born to mothers with obesity with those born to mothers without obesity, the researchers identified clear differences in the composition and diversity of gut bacteria during early life.

Reduced microbial diversity and altered metabolic pathways

The analysis showed that infants of mothers with obesity had significantly lower gut microbial diversity. In addition, these infants had a higher abundance of bacterial species associated with fat metabolism.

These differences were most pronounced during the first three months of life, a period widely recognised as critical for the establishment of the gut microbiome and for metabolic programming.

“During the first three months of life, we observed what appears to be a shift in how gut bacteria process nutrients – with a tendency toward fat storage pathways rather than breaking down carbohydrates for energy,” Kozhakhmetov explained.

He noted that this early metabolic pattern may have implications for how energy balance is regulated later in life.

Opportunities for early intervention

The researchers suggest that their findings open the door to preventive strategies during infancy. Kozhakhmetov highlighted that understanding these early microbial shifts could inform interventions aimed at promoting healthier metabolic outcomes.

This discovery, he said, “opens up possibilities for early intervention”, including approaches such as targeted probiotics or tailored dietary guidance designed to support a more balanced gut microbiome and potentially reduce future metabolic risk.

Beyond metabolism – immune and appetite regulation

The implications of the findings may extend beyond metabolism alone. The researchers propose that maternal obesity could also influence immune system development and appetite regulation in children through microbial transmission.

“We tend to think that we only pass on our genes to our children. But our research suggests that we may also pass on our bacteria – and the type of bacteria a child inherits could have important effects on their long-term health, potentially influencing their health trajectory as they grow,” Kushugulova said.

This perspective reinforces the idea that early-life exposures play a significant role in shaping health across the life course.

Placing the findings in context

The study, published in the journal Biomedicines, adds to a growing body of research highlighting the importance of the early-life microbiome. Previous studies have linked maternal weight status and gut dysbiosis to disrupted nutrient metabolism, inflammation, and changes in immune, metabolic, or neurodevelopmental outcomes in children.

As obesity during pregnancy becomes increasingly common worldwide, the authors argue that maternal health should be viewed as a key determinant not only of pregnancy outcomes, but also of a child’s longer-term metabolic health.

Implications for future research and practice

The researchers conclude that interventions targeting the gut microbiota during early infancy may represent a promising avenue for reducing health risks associated with maternal obesity. Further research will be needed to determine which strategies are most effective, when they should be implemented, and how they can be integrated into routine maternal and child healthcare.

Taken together, the findings underline the importance of addressing obesity before and during pregnancy, while also highlighting the potential of microbiome-focused approaches to support healthier outcomes for future generations.

CCH insight:

Evidence for the role of the gut microbiome in obesity and metabolic health continues to grow. This study is ground-breaking in demonstrating that maternal obesity influences the new-born child’s microbiome, potentially priming the child for health challenges later in life right from their first few weeks of life. On the positive side, this offers the potential to identify babies at risk of metabolic diseases from a very early stage of life, and also the opportunity for early interventions though diet, pre- and probiotics.

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Internalised Weight Stigma Places Heavy Emotional Burden on People Seeking Bariatric Care, Indian Study Finds

Key Takeaways:

• More than 71 percent of participants preparing for metabolic and bariatric surgery reported high levels of internalised weight bias, with many expressing self-blame, shame, and reduced self-worth.
  
• Younger individuals and those with a higher BMI reported stronger internalised stigma, which affected emotional well-being, social relationships, and readiness to seek treatment.
  
• Researchers and clinicians stress that obesity is a chronic disease, not a personal failing, and warn that stigma significantly harms mental health and delays access to appropriate care.
  
  

Introduction

A new study has highlighted the profound emotional and psychological toll experienced by people living with obesity who are preparing for metabolic and bariatric surgery. The research found that internalised weight bias is widespread among individuals seeking specialist care, with many reporting depressive symptoms, reduced self-esteem, and deep feelings of self-criticism linked to their weight.

The pilot study, titled The Burden from Within—An Indian Pilot Study on Weight Bias Internalisation, was published in Obesity Surgery, the international journal of the International Federation for the Surgery and Other Therapies for Obesity (IFSO).

Weight stigma beginning in childhood and persisting into adulthood

Lead author Dr Aparna Govil Bhasker, a Mumbai-based bariatric surgeon at the MetaHeal Laparoscopy and Bariatric Surgery Centre, told The Indian Express that stigmatising experiences often begin early in life. She explained that weight-related bullying is common during childhood and continues into adulthood for many people.

“People living with obesity are frequently judged as lazy or lacking willpower. Negative media portrayals, especially weight-based memes and stigmatising content, only deepen these harmful beliefs. Post-pandemic trends show that online negativity toward obesity has grown even stronger,” she said.

Study design and participant profile

To assess the emotional impact of obesity on people seeking surgical intervention, the research team evaluated 142 participants using the validated Weight Bias Internalization Scale (WBIS). Of the total cohort, 78.9 percent were women, and all participants had a body mass index of at least 27.5 kg/m².

Researchers examined total WBIS scores, associations with age, and correlations with BMI to understand how internalised stigma manifests in individuals preparing for metabolic and bariatric surgery.

High prevalence of internalised weight bias

The study revealed striking levels of internalised stigma:

• More than 71.1 percent of participants scored above the neutral benchmark on the WBIS, indicating widespread internalisation of negative weight-based beliefs.
  
• Around 74.6 percent reported feeling depressed about their weight.
  
• More than half felt less attractive because of their weight.
  
• More than one-third questioned their own competence.

The findings indicate that weight stigma does not simply come from external sources. Many participants had come to believe the negative stereotypes directed at them.

Self-judgement, self-hate, and social avoidance

The report found that more than half of the individuals surveyed expressed intense self-criticism, including feelings of self-hatred related to their weight. Many participants described weight as a defining measure of their personal worth.

Social relationships were also severely affected. Approximately 45.8 percent of participants questioned why anyone they considered attractive would want to date them. Half believed they did not deserve a fulfilling social life until they lost weight.

The data also showed that younger participants experienced stronger internalised bias, while those with higher BMI levels demonstrated deeper self-directed stigma.

“This shows that obesity status and internalisation of weight bias affect social interactions, connections, and relationships, which can have a long-lasting impact on the life course of an individual’s personal, emotional, occupational, and financial trajectory,” Dr Govil Bhasker said.

Obesity rising rapidly in India but not recognised as a disease

The researchers noted that obesity rates in India have nearly doubled since 2005. Data from the fifth National Family Health Survey (2019–21) show that 24 percent of women and 22.9 percent of men aged 15 to 49 years live with overweight or obesity.

Despite this rapid rise, obesity is not officially classified as a disease in India. Dr Govil Bhasker argued that the findings underline the deep societal stigma embedded in attitudes toward obesity.

“Patients often feel ashamed, guilty, and discouraged. They endure years of negative comments, judgment, and misinformation, and over time, these negative experiences become internalized. This affects their self-worth and mental health and can delay their decision to seek proper treatment. Obesity is a chronic disease, not a personal failure, and supporting patients emotionally is just as important as helping them medically,” she said. She added that targeted interventions are urgently needed.

Stigma’s broad impact on mental and physical health

Dr Vishakha Jain, Professor of Medicine at AIIMS BibiNagar and one of the study’s co-authors, emphasised that stigma infiltrates every aspect of daily life.

She explained that persistent stigma affects physical health, mental well-being, occupational performance, and social relationships. It can contribute to unhealthy eating patterns and biological stress responses, including increased inflammation.

“Together, these pressures create a cycle of self-blame and prejudice, often making individuals feel undeserving of care,” Dr Jain said.

Conclusion

The study provides compelling evidence that internalised weight stigma is highly prevalent among people preparing for bariatric care in India and that it carries profound psychological, social, and behavioural consequences. The authors urge greater recognition of obesity as a chronic disease and call for emotional as well as medical support for individuals affected.

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Manchester Launches Landmark Five-Year Mounjaro Trial to Assess Real-World Outcomes

Key Takeaways:

• A five-year real-world trial in Greater Manchester will evaluate the long-term health, employment, and quality-of-life effects of the anti-obesity medication tirzepatide.
  
• Up to 3,000 people will participate, with recruitment taking place through GP practices to reflect everyday clinical conditions.
  
• The study is part of a £279 million partnership between Eli Lilly and the UK government aimed at addressing obesity and improving population health.
  
  

Introduction: A major real-world test of tirzepatide

A five-year clinical study has begun in Greater Manchester to examine the real-world effectiveness of the anti-obesity medication tirzepatide, marketed in the United Kingdom as Mounjaro. The trial aims to understand how the treatment affects long-term health outcomes when delivered through primary care. The first participants have now been enrolled after visiting their GP, marking the formal start of the project.

Scope and scale of the trial

Up to 3,000 people are expected to take part in what is described as a first-of-its-kind real-world study. The trial forms part of a broader £279 million initiative jointly developed by US pharmaceutical company Eli Lilly and the UK government. The aim is to evaluate new ways of addressing major public health challenges, including obesity and related long-term conditions.

Professor Martin Rutter, professor of cardiometabolic medicine at the University of Manchester, emphasised the focus on early intervention. He explained that the research will assess “how effective early intervention is in tackling obesity”, and will examine a wide range of clinical and social outcomes.

What is tirzepatide?

Tirzepatide is an injectable medication that works by mimicking a hormone that helps people feel fuller for longer, thereby suppressing appetite. While marketed as Mounjaro in the UK, it is sold under the brand name Zepbound in the United States.

Clinical trials have previously shown that people receiving Mounjaro experienced up to 20 percent weight loss after 72 weeks of treatment. The Greater Manchester study will build on this evidence by measuring how the medication performs in routine practice rather than controlled trial conditions.

Real-world outcomes beyond weight

A distinctive feature of the trial is its focus on long-term and practical indicators of wellbeing. Researchers will assess health metrics but will also study broader outcomes such as employment status, sick-day absences, and quality of life. These measures are particularly relevant given the significant economic and social impact of obesity.

According to Health Secretary Wes Streeting, illnesses linked to obesity currently cost the NHS £11 billion annually. In Greater Manchester alone, approximately 600,000 adults live with obesity, said Mark Fisher, chief executive officer of the NHS Greater Manchester Integrated Care Board.

A 2023 report by Health Innovation Manchester also estimated that obesity costs the region more than £3 billion each year when NHS treatment, social care, and the impact on quality of life are taken into account.

Role of primary care in the study

The trial is major in part because it is being delivered through GP practices, providing insights into how tirzepatide performs when prescribed in everyday settings. Dr Imran Ghafoor, GP Partner at Peterloo Medical Centre in Middleton, highlighted the importance of local trust and accessibility. He stated that patients see their GP practice as a “familiar and accessible space”, adding that the research will help “test solutions tailored to real lives”.

A diverse participant group

Professor Rutter, who also serves as the trial’s chief investigator, noted that the study intends to evaluate the medication’s health effects “in a diverse group of individuals”. This emphasis on diversity aims to ensure that the findings reflect the varied experiences of people living with obesity across the region.

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Early-life Exposure to Fat-related Food Odours May Shape Lifelong Obesity Risk

Key Takeaways: 

• Early exposure to fat-related food odours during development may prime the brain and body for heightened metabolic responses to high-fat foods later in life.
  
• Sensory cues from a maternal diet, independent of nutritional content or maternal metabolic status, can influence thermogenesis, gene expression, and susceptibility to obesity in adult mice.
  
• Findings suggest a previously underappreciated mechanism of metabolic programming, in which food odours encountered during gestation and lactation can affect lifelong dietary preferences and obesity risk.
  
  

Introduction

A recent study published in Nature Metabolism explores how non-nutritive sensory cues from foods rich in fat, particularly odours, influence the developing brain and metabolic pathways. The research investigates how these early sensory inputs may shape central responses to food cues, metabolic health, and the risk of obesity in adulthood. The findings expand on a substantial body of work showing that early-life nutritional exposure influences later metabolic outcomes, but highlight the specific and previously overlooked contribution of fat-related odours.

Maternal obesity and early nutritional exposure

How maternal diet affects offspring

Developmental exposure to a maternal diet high in calories and fat is a well-recognised risk factor for obesity and metabolic disorders throughout life. Numerous studies have linked maternal high-fat diet (HFD) consumption with outcomes such as excess gestational weight gain, insulin resistance, and increased adiposity in mothers, all of which may contribute to lifelong metabolic vulnerability in offspring.

Despite these strong associations, the specific components of HFDs that drive metabolic programming remain only partly understood. While nutrients themselves contribute directly to energy balance and metabolic pathways, foods also contain non-nutritive sensory elements, including volatile odours. Fetuses and newborns experience these odours during development, meaning that sensory exposure is layered on top of nutritional exposure.

Sensory memories formed early in life

Perinatal olfactory experiences contribute to the formation of sensory memories that influence food preferences and eating habits into adulthood. The authors emphasise that understanding how non-nutritive cues from a maternal HFD influence long-term dietary preferences and metabolic responses is crucial for clarifying early-life drivers of obesity risk.

Study approach

Separating nutritional and sensory influences

To distinguish nutritional caloric components from sensory components, the researchers designed an isonutritional model using a standard normal chow diet (NCD) infused with fat-related odours. This bacon-flavoured diet (BFD) enabled researchers to expose mice to fat-related sensory cues without increasing calorie content.

• BFD: NCD enriched with bacon odours, designed to mimic the odour profile of a standard lard-based high-fat diet (HFDlard).
  
• HFDbutter: A butter fat-based HFD used to represent a non-pork, high-fat option.
  

This design allowed the researchers to isolate the effect of fat-related sensory exposure during development, independent of maternal metabolic changes such as insulin resistance, weight gain, or altered lipid levels.

Odour profile analysis

A detailed chemical characterisation identified 155 volatile compounds across the diets, including aldehydes, ketones, and alcohols. Hierarchical clustering revealed:

• HFD and HFDlard shared high sensory similarity
  
• Both differed significantly from HFDbutter and NCD
  
• BFD’s odour profile closely matched HFDlard, yet its nutritional profile remained identical to NCD
  

These findings confirmed that BFD was an appropriate tool for studying sensory-specific metabolic programming.

Sensory cues and neural activation

Experimental analyses showed that fat-related food odours induced phosphorylation of S6 in olfactory sensory neurons (OSNs), demonstrating that the odours elicited detectable neural activation. Mice perceived BFD as more similar to HFDlard than to NCD, reinforcing that the sensory model accurately represented fat-related olfactory cues.

Early exposure and adult metabolism

Developmental exposure primes obesogenic responses

Control mice exposed only to NCD during development (NCDdev) showed no changes in interscapular brown adipose tissue (iBAT) thermogenesis or hepatic mechanistic target of rapamycin (mTOR) phosphorylation when later exposed to HFDlard odours. In contrast, mice developmentally exposed to BFD (BFDdev) displayed significant increases in both iBAT temperature and hepatic p-mTOR when encountering these odours for the first time in adulthood.

This indicates that early exposure to fat-related odours enhances metabolic responsiveness to high-fat sensory cues later in life.

Independent of maternal obesity

Importantly, these heightened responses occurred without maternal insulin resistance, adiposity, or weight gain. This demonstrates that sensory exposure alone, rather than changes in maternal metabolism, can programme obesity risk.

Sex-specific sensitivity

• Females: Lactation appeared to be the most sensitive developmental window for programming effects.
  
• Males: Required exposure throughout the entire developmental period to exhibit similar heightened metabolic responses.
  
  
  

Responses to different high-fat diets

Eight-week-old BFDdev and NCDdev mice were also exposed to HFDbutter. The aim was to test whether heightened susceptibility required precise sensory matching or whether vulnerability generalised across high-fat diets.

Findings showed that early exposure to fat-related sensory cues increased obesity susceptibility even when adult exposure involved a high-fat diet with different sensory characteristics. This suggests that early sensory programming affects broad metabolic pathways rather than specific flavour-diet associations.

While a perfect sensory match between early and later exposure was not necessary, some degree of sensory similarity still appeared relevant in shaping metabolic outcomes.

Changes in the maternal environment

The study found that feeding mothers BFD altered the volatile odour profile of both amniotic fluid and milk. These changes exposed developing offspring to fat-related sensory information during gestation and lactation, influencing their early sensory learning and shaping later responses to food.

Impairments in thermogenesis and metabolic flexibility

BFDdev mice demonstrated reduced iBAT thermogenesis compared with NCDdev controls. They also exhibited lower expression of thermogenic-related genes in iBAT, including:

• Cidea
• Pparg
  

These findings indicate that developmental exposure to fat-related odours impairs metabolic flexibility and weakens homeostatic responses to hypercaloric diets in adulthood.

Altered neuronal responses to fat

The researchers reported a specific impairment in Agouti-related peptide (AgRP) neuronal responsiveness to dietary fat in BFDdev mice. These neurons help regulate hunger and energy balance. Despite this, responses to major hormonal signals remained unaffected, suggesting that sensory-specific pathways were selectively disrupted.

Conclusion

The study provides compelling evidence that early-life exposure to fat-related food odours can contribute to long-term obesity risk by shaping metabolic and neuronal responses long before an individual consumes high-fat foods. These sensory cues act independently of calorie exposure and maternal metabolic health, highlighting a novel pathway through which obesity susceptibility may be programmed. Although the research was conducted in mice, it underscores the potential importance of early sensory environments in influencing metabolic health across the lifespan.

CCH insights:

This is fascinating research. We already know that the diet of a pregnant woman can influence the dietary preferences and health outcomes of her child, but now it appears odours of certain foods during pregnancy may have similar affects. It adds an intriguing new line of investigation in terms of the Developmental Origins of Health and Disease. However, we must remember this study was in mice, using bacon odours to mimic a lard-based high fat diet, so we are a long way from being able to draw conclusions about real world implications for pregnant women.

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Study Suggests GLP-1 Medications May Reduce Frailty Progression in Older Adults

Key Takeaways: 

• Older adults with type 2 diabetes who begin SGLT-2 inhibitors or GLP-1 receptor agonists show slower frailty progression over one year compared with those starting other diabetes therapies.
  
• The analysis, based on a large national Medicare dataset, suggests these medications may offer benefits beyond glycaemic and cardiovascular control, potentially supporting strength, mobility, and functional independence.
  
• The protective effect was not fully explained by fewer cardiovascular or safety events, indicating a possible direct influence of these drug classes on frailty itself.
  
  

Emerging evidence that newer diabetes drugs may protect against frailty

A new study has found that older adults living with type 2 diabetes who initiate treatment with sodium–glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists experience significantly slower progression of frailty over a 12-month period compared with those starting alternative diabetes medications. The findings point to a potential added advantage of these therapies in helping older adults maintain physical resilience, strength, and independence, complementing their established effects on blood glucose regulation and cardiovascular risk reduction.

Study overview and methods

The research, published in Diabetes Care and titled “Sodium–Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Frailty Progression in Older Adults With Type 2 Diabetes”, examined a large national cohort of older adults in the United States who had recently begun different classes of diabetes medication.

The investigators analysed a 7 per cent sample of Medicare claims data, enabling real-world tracking of over one year of health outcomes. Frailty progression was assessed using a validated claims-based Frailty Index (CFI), which ranges from 0 to 1 and reflects the cumulative presence of age-related health deficits. Higher CFI scores indicate more severe frailty.

Key findings – slower frailty progression with SGLT-2 and GLP-1 therapies

Older adults newly prescribed a GLP-1 receptor agonist, such as semaglutide (Ozempic) or liraglutide (Victoza), demonstrated a mean CFI change of –0.007 (95 per cent CI: –0.011 to –0.004) compared with matched new users of DPP-4 inhibitors. Those initiating SGLT-2 inhibitors, including empagliflozin (Jardiance) and dapagliflozin (Farxiga), experienced a mean change of –0.005 (95 per cent CI: –0.008 to –0.002).

These figures represent a statistically significant slowing in frailty progression over the study period. In contrast, people beginning sulfonylureas did not show a meaningful difference relative to DPP-4 inhibitor users.

Importantly, the study found that cardiovascular events and other safety-related health issues explained only a small proportion of the protective association. This suggests that these classes of medications may exert a more direct biological effect on mechanisms related to frailty, such as inflammation, physical function, or metabolic stress.

Why frailty matters in older adults with type 2 diabetes

Frailty is common among older adults and especially prevalent in people living with type 2 diabetes. Previous research indicates that 10–15 per cent of adults over the age of 65 meet criteria for frailty, with substantially higher rates among those with diabetes. Multiple factors contribute to this increased vulnerability, including chronic low-grade inflammation, accelerated muscle loss, cardiovascular disease, and the overall physiological strain of managing a long-term condition.

Frailty is linked to an elevated risk of falls, disability, hospital admission, diminished quality of life, and reduced survival. Because frailty is difficult to reverse once it becomes established, clinicians and researchers have prioritised strategies that can delay or slow its progression. The study’s findings therefore hold particular significance for geriatric diabetes care.

Clinical implications – a possible shift in medication decision-making

The results may encourage clinicians to consider the broader health trajectory of older adults when selecting diabetes medications, especially as SGLT-2 inhibitors and GLP-1 receptor agonists are increasingly used for combined glycaemic, cardiovascular, and renal protection.

Chanmi Park, MD, MPH, the study’s lead author and Assistant Scientist I at the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, highlighted this point:

“While SGLT-2 inhibitors and GLP-1 receptor agonists are primarily prescribed for blood sugar control and heart protection, our findings show they may also help older adults with diabetes stay stronger and less vulnerable to health setbacks. Because frailty is common, serious, and hard to reverse, this could meaningfully change how clinicians think about medication choices for ageing patients.”

A promising step towards more holistic diabetes care

The study adds to a growing body of literature suggesting that newer diabetes medications may offer multidimensional benefits. By potentially supporting physical resilience in addition to metabolic and cardiovascular health, SGLT-2 inhibitors and GLP-1 receptor agonists could become central tools in promoting healthier ageing for people living with type 2 diabetes.

Further research will be needed to better understand the biological mechanisms at play and to determine whether similar benefits appear in more diverse patient populations and longer-term studies.

CCH insight:

The results of this study are very encouraging from the perspective of GLP-1 medications and muscle mass/strength. There are currently concerns in some quarters about potential excess loss of muscle mass and sarcopenia accompanying weight loss from these drugs. However, this study points towards a positive impact on physical strength and function from GLP-1 therapy.

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Mice Study Connects Soybean Oil Intake to Liver Changes and Obesity

Key Takeaways: 

• New research in mice suggests that weight gain linked to soybean oil is driven by the metabolic products of linoleic acid rather than the oil itself.
  
• Genetically engineered mice resistant to obesity on a high-fat soybean oil diet produced fewer oxylipins and showed healthier liver function.
  
• Scientists believe differences in human genetics, enzyme levels, and metabolic stress may influence people’s susceptibility to soybean-oil-related metabolic effects.
  
  

A closer look at soybean oil and obesity

Soybean oil is the most widely consumed cooking oil in the United States and is a key ingredient in many processed foods. A growing body of research has associated high intake of soybean oil with weight gain in animals. A new study from the University of California, Riverside (UCR), published in the Journal of Lipid Research, provides fresh insight into why this may occur.

Researchers found that mice consuming a high-fat diet rich in soybean oil gained considerable weight. However, a separate group of genetically engineered mice did not, despite eating the same diet. These altered mice carried a slightly different version of a liver protein that affects the expression of hundreds of genes involved in fat metabolism.

The findings point toward a metabolic mechanism that may help explain differences in weight gain among individuals exposed to similar diets.

“This may be the first step toward understanding why some people gain weight more easily than others on a diet high in soybean oil,” said Sonia Deol, a UCR biomedical scientist and corresponding author of the study.

The role of HNF4α in fat metabolism

In humans, both forms of the liver protein known as HNF4α occur naturally. However, the alternative version typically appears only under certain conditions, such as chronic illness, prolonged fasting, metabolic stress, or alcoholic fatty liver disease. These variations, combined with factors such as age, sex, medication use, and underlying genetics, may influence how different people respond to high levels of soybean oil in their diet.

The UCR team believes that the altered form of HNF4α in genetically engineered mice changes how the body processes linoleic acid, a major fatty acid in soybean oil.

Building on earlier research

The study adds to previous findings from the same research group.

“We’ve known since our 2015 study that soybean oil is more obesogenic than coconut oil,” said Frances Sladek, a UCR professor of cell biology. “But now we have the clearest evidence yet that it’s not the oil itself, or even linoleic acid. It’s what the fat turns into inside the body.”

One of the major metabolic products of linoleic acid is a group of molecules called oxylipins. These compounds are associated with inflammation, fat accumulation, and other metabolic changes.

Oxylipins and their link to weight gain

Mice engineered to produce the alternative form of HNF4α showed markedly lower levels of oxylipins in their livers, despite consuming a high-fat soybean oil diet. They also had healthier liver profiles and enhanced mitochondrial function. Improved mitochondrial activity may help explain their resistance to weight gain.

Researchers pinpointed specific oxylipins derived from both linoleic acid and alpha-linolenic acid (another fatty acid found in soybean oil) that appeared necessary for weight gain in regular mice.

However, the picture is complex. Even though transgenic mice on a low-fat diet showed elevated oxylipin levels, they did not become obese. This suggests that while these molecules contribute to weight gain, they are unlikely to be the sole drivers. Other metabolic conditions must also play a role.

Genetic variation in enzyme levels

Further analysis revealed that the modified mice had far lower levels of two key enzyme families responsible for converting linoleic acid into oxylipins. These enzymes are highly conserved across all mammals, including humans, and can vary significantly from person to person based on factors such as genetics and diet.

The scientists also observed that oxylipin levels in the liver, rather than in the bloodstream, were correlated with body weight. This indicates that standard blood tests may not reliably detect early metabolic disturbances linked to diet.

Soybean oil’s rise in the American diet

Soybean oil consumption in the United States has risen dramatically over the past century. It has increased from around 2 percent of total daily calories to almost 10 percent. Although soybeans provide protein and the oil contains no cholesterol, modern diets deliver far greater quantities of linoleic acid than the body is likely evolved to manage.

In line with this, the UCR study found that soybean oil intake was associated with increased cholesterol levels in mice despite the oil containing no dietary cholesterol. This reflects the complex interplay between dietary fats and internal metabolic pathways.

Questions for future research

The team now aims to understand precisely how oxylipin formation leads to weight gain and whether oils with similarly high linoleic acid content – including corn, sunflower, and safflower oils – trigger comparable effects.

“Soybean oil isn’t inherently evil,” said Deol. “But the quantities in which we consume it is triggering pathways our bodies didn’t evolve to handle.”

Although the researchers have no plans for human trials, they hope the findings will inform future studies and guide public health policy.

“It took 100 years from the first observed link between chewing tobacco and cancer to get warning labels on cigarettes,” Sladek noted. “We hope it won’t take that long for society to recognise the link between excessive soybean oil consumption and negative health effects.”

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WHO Warns of Severe Global Shortages of GLP-1 Obesity Medicines as Demand Surges

Key Takeaways: 

• Fewer than one in ten people worldwide who could benefit from GLP-1 medicines such as Wegovy and Mounjaro are currently able to access them, due to major limitations in production, affordability, and health system readiness.
  
• The World Health Organization has issued its first formal guidance on the clinical use of GLP-1 therapies, describing them as “a new chapter” in the treatment of obesity, but emphasising the need for equitable access and comprehensive lifestyle support.
  
• Without urgent action, global obesity prevalence is projected to double to two billion people by 2030, with associated economic costs reaching three trillion US dollars.
  
  

WHO Issues first guidance on GLP-1 medicines amid severe supply constraints

The World Health Organization has warned that fewer than one in ten people globally who could benefit from modern GLP-1 obesity medicines are currently able to obtain them, despite the scale of the obesity epidemic and the transformative clinical potential of drugs such as Wegovy and Mounjaro.

With more than one billion people worldwide now living with obesity, the WHO has called for far more widespread, affordable, and equitable access to GLP-1 therapies. Projections indicate that more than two billion people will be living with obesity by 2030 unless governments implement decisive action. The economic burden is expected to rise steeply, with global costs anticipated to reach three trillion US dollars by the same date.

Dr Tedros Adhanom Ghebreyesus, WHO Director-General, stressed that modern pharmacological treatments must be understood as part of a long-term care approach. He stated: “Our new guidance recognises that obesity is a chronic disease that can be treated with comprehensive and lifelong care. While medication alone will not solve this global health crisis, GLP-1 therapies can help millions overcome obesity and reduce its associated harms.”

The WHO has already added GLP-1 medicines to its essential medicines list for people who are overweight and living with diabetes, signalling that countries are advised to provide access to them. The organisation’s new guidance, described as a “special communication” aimed at clinicians, sets out for the first time its formal position on the value, limitations, and safe use of these drugs.

A new chapter in obesity treatment

The WHO notes that GLP-1 therapies represent “more than a scientific breakthrough”. They mark a decisive shift in how obesity is conceptualised, moving away from viewing it solely as a “lifestyle condition” and towards recognising it as a complex, preventable, and treatable chronic disease. The statement published in the Journal of the American Medical Association asserted: “GLP-1 therapies … have emerged as an important innovation in addressing the global obesity challenge. The advent of these medications represents a tipping point in the treatment of obesity, its complications and related co-morbidities.”

The WHO highlighted increasing evidence that GLP-1 therapies may also reduce the risk of several serious conditions, including heart attacks, strokes, type 2 diabetes, high blood pressure, elevated cholesterol, sleep apnoea, and kidney and arterial disease.

However, the organisation emphasised that these medicines must always be paired with holistic support. Individuals prescribed GLP-1s should receive advice on nutrition, physical activity, and behavioural counselling to maintain weight loss and improve long-term health outcomes. The WHO also reiterated that pregnant women should not use GLP-1 therapies.

Global access limited by production, affordability, and system capacity

Despite rising demand, global production capacity remains a major barrier. The WHO estimates that even under the most optimistic forecasts, manufacturers could produce enough GLP-1 medicines for only about 100 million people. This represents less than 10 per cent of the more than one billion who could benefit.

High prices, limited manufacturing capability, and supply chain constraints all significantly restrict access. The WHO has urged pharmaceutical companies to expand production rapidly and to reduce the prices of medications such as Mounjaro and Ozempic to prevent people in low-income countries from being excluded.

The guideline calls for measures such as voluntary licensing, through which patent-holding companies allow other manufacturers to produce low-cost generic versions. This pathway may soon become more viable as key patents expire. The patent on semaglutide, the active ingredient in Novo Nordisk’s Wegovy, is due to expire in several countries in 2026. Once this occurs, manufacturers in India, Canada, China, Brazil, Turkey, and other jurisdictions will be able to develop and sell more affordable versions.

The WHO also underscored three persistent barriers that must be addressed to achieve global access:

1. Limited production capacity, availability, and affordability.
   
2. Health system readiness to prescribe and monitor the medicines.
   
3. Universal access to healthcare services.
   

Dr Tedros stressed the organisation’s “greatest concern is equitable access”.

Calls for national action on prevention and supportive environments

While pharmacotherapy can assist individuals living with obesity, the WHO stated that countries must continue to prioritise prevention and create healthier environments. This includes promoting physical activity, improving food systems, and ensuring that population-level interventions accompany advances in medical treatment.

How GLP-1 obesity medicines work

GLP-1 medicines work by mimicking a natural hormone that slows digestion, suppresses appetite, and increases feelings of fullness. This results in people eating less and typically losing weight within a few weeks of starting treatment.

In the United Kingdom, GLP-1 medicines are prescription-only and can only be supplied following clinical assessment by a healthcare professional. Some formulations are available through the NHS, although many are obtained privately. A black market for these medicines exists, and the WHO and UK regulators warn that people should avoid unregulated sources such as beauty salons or social media sellers.

Research suggests that people often regain much of the weight within a year after stopping GLP-1 therapy, as physiological hunger cues return. This further reinforces the need for comprehensive, long-term behavioural support.

Global obesity burden and associated risks

Obesity affects people in every country and was associated with 3.7 million deaths worldwide in 2024, according to the WHO. Being overweight or living with obesity increases the risk of numerous serious health conditions, including type 2 diabetes, cardiovascular disease, stroke, and several cancers. The WHO’s statement highlights the immense public health implications if access to effective interventions continues to lag far behind global need.

Expert commentary

The WHO statement was authored by senior clinicians Francesca Celletti, Luz De Regil, and Jeremy Farrar, the organisation’s Assistant Director for Health Promotion and Disease Prevention and Control. Dr Farrar formerly served as WHO Chief Scientist and Director of the Wellcome Trust in London.

Katherine Jenner, Executive Director of the United Kingdom’s Obesity Health Alliance, emphasised that medicines are only part of the solution. She stated: “Weight loss drugs have an important role to play, but they are not a silver bullet. In the United Kingdom right now, access is still limited, supply is fragile, and NHS use is tightly targeted. These powerful medicines can help individuals with chronic obesity, but they are not suitable for everyone and must be accompanied by comprehensive support to be used safely and effectively. Evidence shows that most people regain weight once they stop taking these drugs, and we cannot medicate two-thirds of the population indefinitely.”

CCH insight:

The limited supply of GLP-1 medicines globally is of course frustrating, but until new drugs come to market, and just liraglutide, semaglutide and tirzepatide available, this is likely to continue. All three of these drugs are polypeptides, delivered via injection ‘pens’ and must be refrigerated, so they are expensive and complicated to produce. However, new GLP-1 medications are in development which should improve access and reduce costs, such as orforglipron – a small molecule which is easier to produce and can be taken orally in pill form.

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WHO Issues First Global Guideline on GLP-1 Therapies for Treating Obesity

Key Takeaways: 

• WHO has released its first global guideline on the use of GLP-1 therapies for treating obesity as a chronic, relapsing disease, offering conditional recommendations for adults.
  
• While the medicines show meaningful benefits, WHO stresses that medication alone will not reverse the obesity crisis and that person-centred, lifelong care is essential.
  
• Concerns remain about long-term safety data, affordability, availability, and the potential for widening global health disparities without deliberate policy action.
  
  

Introduction: A new milestone in global obesity care

The World Health Organization (WHO) has issued its first global guideline on the use of Glucagon-Like Peptide-1 (GLP-1) therapies for treating obesity, a chronic and relapsing disease affecting more than one billion people worldwide. Obesity contributes to 3.7 million deaths globally each year, and without urgent action the number of people living with obesity is projected to double by 2030.

The new guideline follows the decision made in September 2025 to add GLP-1 therapies to the WHO Essential Medicines List for managing type 2 diabetes in individuals at high risk. With this new document, WHO provides its first formal, conditional recommendations on the use of GLP-1 therapies specifically for obesity as part of a comprehensive treatment approach that includes healthy diets, regular physical activity, and professional health support.

“Obesity is a major global health challenge that WHO is committed to addressing by supporting countries and people worldwide to control it, effectively and equitably. Our new guidance recognises that obesity is a chronic disease that can be treated with comprehensive and lifelong care,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “While medication alone won’t solve this global health crisis, GLP-1 therapies can help millions overcome obesity and reduce its associated harms.”

The global and economic burden of obesity

Obesity is a complex, chronic disease and a major driver of noncommunicable conditions including cardiovascular diseases, type 2 diabetes, and some cancers. It also worsens outcomes for people who develop infectious diseases.

The global economic burden is profound. The worldwide cost of obesity is projected to reach US$ 3 trillion every year by 2030 due to increased healthcare demands and the rising costs of managing obesity-related complications. WHO hopes that clear guidance on the use of GLP-1 therapies will support efforts to reduce escalating healthcare expenditure while improving outcomes for people affected by obesity.

A landmark policy shift: WHO’s conditional recommendations

WHO’s new guideline sets out two key conditional recommendations based on currently available evidence.

1. Use of GLP-1 therapies in adults living with obesity

WHO states that GLP-1 therapies may be considered for long-term treatment in adults, excluding pregnant women. The medicines have demonstrated clear efficacy in supporting weight loss and improving metabolic outcomes. However, the recommendation remains conditional due to several concerns:

• Limited long-term data on safety, durability, maintenance, and outcomes following discontinuation
• High costs of treatment
• Insufficient readiness of health systems to support widespread use
• Possible negative effects on health equity
  

2. Combining GLP-1 therapies with intensive behavioural interventions

WHO also recommends that adults living with obesity and prescribed GLP-1 therapies may be offered structured behavioural interventions, including support for dietary changes and increased physical activity. This recommendation reflects low-certainty evidence suggesting that combining medication with lifestyle interventions may yield better outcomes.

Medication alone will not reverse the obesity crisis

Although GLP-1 therapies represent the first highly effective pharmacological treatment for adults living with obesity, WHO emphasises that medication on its own is insufficient. Obesity must be addressed as both an individual and societal challenge. The guideline calls for a fundamental shift toward comprehensive strategies built on three pillars:

1. Creating healthier environments through population-level policies that promote health and prevent obesity.
2. Protecting people at high risk by using targeted screening and structured early interventions.
3. Ensuring person-centred, lifelong care for people living with obesity, recognising the chronic nature of the disease.
   
   
   

Implementing the guideline: Equity, system readiness and global access

WHO notes that fair access to GLP-1 therapies must be prioritised. Without deliberate policies, these medicines could deepen existing global health inequalities. System readiness, affordability, and supply capacity are major concerns.

Even with rapid increases in manufacturing, GLP-1 therapies are expected to reach fewer than 10 percent of people who could benefit from them by 2030. WHO urges global leaders to consider approaches that expand access, such as:

• Tiered pricing
• Pooled procurement mechanisms
• Voluntary licensing arrangements
  

These measures could help prevent widening disparities as demand expands.

Development of the guideline

The guideline was developed in direct response to requests from WHO Member States seeking actionable direction on obesity care. The process involved:

• Extensive assessment of available scientific evidence
• Input from global stakeholders
• Engagement with people who have lived experience of obesity
  

This document forms a core component of the WHO acceleration plan to stop obesity and will be updated regularly as new evidence emerges.

During 2026, WHO intends to work with partners to create a transparent and equitable prioritisation framework to ensure that individuals with the greatest medical need receive treatment first.

Notes to editors

About GLP-1 therapies for obesity

WHO defines obesity in adults as having a Body Mass Index (BMI) of 30 or above. GLP-1 receptor agonists help lower blood glucose, support weight loss, reduce cardiovascular and renal risks, and can reduce early mortality in people with type 2 diabetes.

This guideline provides recommendations for three GLP-1 agents used in the long-term treatment of obesity in adults:

• Liraglutide
• Semaglutide
• Tirzepatide
  

Falsified and substandard products

The surge in global demand has contributed to the spread of falsified and substandard GLP-1 products. WHO stresses that safe access requires:

• Prescription and distribution through regulated, qualified healthcare providers
• Strong oversight and monitoring
• Patient education
• International cooperation to safeguard public health
  

The organisation warns that falsified or substandard medicines threaten both patient safety and public trust.

CCH insight:

This new guideline is very welcome. The World Health Organisation has been a little slow in recognising obesity as a chronic relapsing disease and the importance of GLP-1 medications as a very important development in obesity treatment. However, these guidelines are comprehensive, consistent with treatment of obesity as a chronic relapsing disease, and recognise the challenges of delivering safe, sustainable, equitable obesity care.

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Novo Nordisk’s Amycretin Emerges as a Strong Next-Generation Obesity and Diabetes Candidate in Early and Mid-Stage Trials

Key Takeaways: 

• Early and mid-stage studies indicate that amycretin delivers substantial, dose-dependent weight loss in people who are overweight or have obesity, as well as in people with type 2 diabetes.
  
• Safety findings remain broadly consistent with GLP-1-based agents, with mainly mild to moderate gastrointestinal effects and no weight-loss plateau observed within study periods.
  
• Novo Nordisk’s new data signal a potentially important successor to semaglutide, strengthening the company’s obesity and diabetes pipeline as it faces patent expirations and competitive pressure from Eli Lilly.
  

Introduction

A new body of evidence published in The Lancet and released by Novo Nordisk suggests that amycretin, an investigational once-weekly therapy targeting multiple metabolic pathways, may offer clinically meaningful weight reduction and glycaemic improvements in adults who are overweight or have obesity, as well as in adults with type 2 diabetes. The findings come as Novo Nordisk aims to consolidate its leadership in the weight-loss market following concerns about semaglutide’s recent performance in Alzheimer’s trials and increasing competition from Eli Lilly.

Amycretin combines actions on the glucagon-like peptide 1 (GLP-1), amylin, and calcitonin receptors. This multi-pathway design is intended to amplify appetite suppression, slow gastric emptying, and improve metabolic control. Amylin’s role is particularly relevant because it complements GLP-1 signalling, and combining these effects may provide more durable weight management than existing single-pathway therapies.

Background

Obesity affects more than one billion people worldwide and increases the risk of conditions such as cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease, and sleep apnoea. Although GLP-1 or GIP receptor agonists have transformed obesity care, many individuals still struggle to meet health goals or encounter diminishing returns over time. Enhancing these therapies with additional hormonal pathways, such as amylin, has been of growing scientific interest.

Amylin, a pancreatic hormone, naturally suppresses appetite, slows digestive transit, and moderates post-meal glucose spikes. When combined with GLP-1 activation, amylin may strengthen satiety signals and support deeper and more sustained weight reduction. Amycretin, a single peptide simultaneously targeting GLP-1, amylin, and calcitonin receptors, represents an effort to leverage these combined mechanisms.

While animal studies have shown potent metabolic effects, the safety, tolerability, and human efficacy of this multi-pathway approach had not been fully established, prompting the recently reported Phase 1b/2a trial and Novo Nordisk’s parallel mid-stage diabetes study.

Phase 1b/2a trial overview (adults who are overweight or have obesity)

Study design

Investigators conducted a five-part, randomised, placebo-controlled Phase 1b/2a trial at a single clinical site in San Antonio, Texas. Eligible adults were aged 18–55 years, had a baseline BMI between 27.0 and 39.9 kg/m², and had no major illnesses such as diabetes. Participants received subcutaneous amycretin or placebo once weekly.

The trial included:

• Part A: Single ascending doses (0.3 mg, 0.6 mg, 1.0 mg).
  
• Part B: Dose escalation to 60 mg over 36 weeks.
  
• Part C: Dose escalation to a 20 mg maintenance dose for the final 12 weeks of a 36-week period.
  
• Part D: Dose escalation to a 5 mg maintenance dose for the final 12 weeks of 28 weeks.
  
• Part E: Dose escalation to a 1.25 mg maintenance dose for the final 12 weeks of 20 weeks.
  

Endpoints and monitoring

The primary endpoint was the incidence of treatment-emergent adverse events. Secondary endpoints included:

• Percentage change in body weight
  
• Pharmacokinetic parameters
  
• Exploratory metabolic biomarkers (fasting glucose and HbA1c)
  

Participants had regular laboratory testing, ECG monitoring, and safety assessments. Analyses were adjusted for baseline weight and missing data.

Phase 1b/2a results

Participant characteristics

Between September 2023 and April 2024, the study enrolled 125 adults. A total of 101 received amycretin and 24 received placebo. Baseline BMIs ranged from 30.0 to 33.1 kg/m² across treatment groups, with an overall mean of 33.4 kg/m². Baseline weights ranged from 83.6 kg to 99.1 kg.

Tolerability and discontinuations

Thirty-eight participants receiving amycretin (37%) and four receiving placebo (17%) discontinued the study. Most discontinuations were not related to safety, and investigators noted that placebo discontinuations appeared consistent with a likely nocebo effect.

Treatment-emergent adverse events occurred in 92% of amycretin recipients and 100% of placebo recipients in Parts B–E. Gastrointestinal effects were most common and included:

• Nausea: 82%
  
• Vomiting: 53%
  
• Diarrhoea: 41%
  

These symptoms generally peaked during dose escalation and diminished afterwards. Dysaesthesia rates varied by cohort, ranging from 6% to 29%, and resolved in all but one participant.

One case of mild gallstone pancreatitis occurred during dose escalation in Part C (2.5 mg), later progressing to a serious recurrent episode that ultimately resolved.

No clinically meaningful ECG abnormalities were detected. A transient early rise in heart rate of about 10 bpm resolved without intervention. Antidrug antibodies appeared in 29% of Part B participants and 21% in Part C.

Weight-loss effects

Weight reduction was rapid, dose-dependent, and sustained. Mean percentage weight losses at end of treatment were:

• 60 mg (week 36): 24.3%
  
• 20 mg (week 36): 22.0%
  
• 5 mg (week 28): 16.2%
  
• 1.25 mg (week 20): 9.7%
  

Placebo groups had much smaller changes: −1.1% (Part B), +1.9% (Part C), +2.3% (Part D), and +2.0% (Part E).

Superiority to placebo emerged by week 4 and continued to widen without evidence of plateau during the maintenance phases. Repeated-measures models produced nearly identical weight-loss estimates.

Metabolic effects

Exploratory findings indicated modest improvements:

• Fasting glucose reductions up to 0.8 mmol/L
  
• HbA1c reductions of 0.6 percentage points in the highest-dose cohort
  

Lipid levels and seated blood pressure remained neutral.

Novo Nordisk’s mid-stage trial in type 2 diabetes

In parallel with the early-stage obesity trial, Novo Nordisk announced promising results from a mid-stage study evaluating amycretin in adults with type 2 diabetes who had inadequate glycaemic control with metformin, with or without an SGLT2 inhibitor. The trial included 448 participants and assessed both once-weekly subcutaneous and oral formulations.

Context and competitive landscape

The announcement came one day after Novo Nordisk reported disappointing Alzheimer’s trial results for semaglutide. With patent expirations approaching and rising competition from Eli Lilly’s amylin-based agent eloralintide, analysts are closely watching amycretin’s performance.

Amycretin is widely viewed as a potential “best-in-class” therapeutic candidate. It follows CagriSema, a combination approach which had raised strong expectations but ultimately delivered less weight loss than anticipated in prior studies.

Key findings

• Weight loss:
  
  • Up to 14.5% weight reduction with once-weekly injections over 36 weeks
    
  • Up to 10.1% weight reduction with the oral formulation
    
  • Both routes showed no weight-loss plateau, suggesting the potential for further reduction with longer treatment durations.
    
• Glycaemic control:
  
  • Statistically significant HbA1c reductions
    
  • Up to 89.1% of participants achieved HbA1c below 7%
    
  • Side-effects were mostly mild gastrointestinal symptoms.
    

Novo Nordisk stated it intends to begin late-stage clinical trials in 2026.

Analyst commentary

BMO Capital analyst Evan Seigerman noted that the data represent progress for Novo Nordisk:
“The data, though not enough to completely change the narrative for Novo, marks a step in the right direction for the company.”

Kepler Cheuvreux analyst David Evans commented on amycretin’s broader potential:
“The level of weight-loss seen bodes well not only for its potential in diabetes but also in obesity.”

Morningstar analyst Karen Andersen projected substantial commercial potential, estimating peak annual sales of $8 billion by 2034, split approximately evenly between diabetes and obesity indications, assuming a 2029 launch.

Conclusion

The combined early- and mid-stage data suggest that amycretin may represent a significant development in obesity and diabetes treatment. Its multi-pathway design has shown robust weight-loss effects across populations and the possibility of improved metabolic outcomes. While long-term safety and efficacy need confirmation in Phase 3 trials, amycretin appears positioned as one of Novo Nordisk’s most important next-generation candidates at a time of high strategic importance for the company.

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Metformin May Help Prevent Recurrence of Atrial Fibrillation After Ablation in Adults with Obesity

Key Takeaways: 

• Adults with obesity who took metformin after AFib ablation had fewer recurrences of atrial fibrillation compared with those receiving standard care alone.
  
• 78% of participants receiving metformin remained free of AFib episodes lasting 30 seconds or more, compared with 58% in the standard care group.
  
• Researchers suggest further large-scale studies are needed to confirm whether diabetes medications such as metformin or GLP-1 receptor agonists could support heart rhythm stability in people with obesity who do not have diabetes.
  
  

Metformin shows promise beyond diabetes treatment

People with atrial fibrillation (AFib) and obesity may experience fewer episodes of irregular heart rhythm after undergoing ablation if they take the diabetes medication metformin in addition to standard care, according to a preliminary presentation of late-breaking science at the American Heart Association’s (AHA) Scientific Sessions 2025, held from 7 to 10 November in New Orleans. The annual meeting is a leading international forum for sharing new research and clinical advances in cardiovascular medicine.

“Lifestyle and risk factor modification efforts are essential to treating AFib and, according to the results of our study, could be aided by taking metformin,” said Dr Amish Deshmukh, lead author and clinical assistant professor of medicine at the University of Michigan in Ann Arbor.

AFib, characterised by an irregular and often rapid heartbeat, is the most common form of heart rhythm disorder. According to the AHA, it can lead to blood clots, stroke, heart failure, or other cardiovascular complications.

Metformin, a long-established and low-cost generic medication, helps regulate blood glucose levels and is most often prescribed to people with Type 2 diabetes. It is widely regarded as a first-line treatment due to its safety, affordability, and efficacy.

Exploring metformin’s role in reducing AFib recurrence

Previous research has indicated that people with diabetes and obesity who take metformin tend to have a lower risk of developing AFib compared with those using other antidiabetic medications. In laboratory studies, metformin has shown direct effects on cardiac cells, including the reduction of abnormal heart rhythms. Building on this evidence, researchers sought to determine whether metformin could help reduce the recurrence of AFib in people with obesity or overweight following catheter ablation.

The Metformin as an Adjunctive Therapy to Catheter Ablation of Atrial Fibrillation (META-AF) study enrolled 99 adults with AFib who were either overweight or obese. All participants underwent catheter ablation – a procedure that targets and removes small areas of heart tissue responsible for irregular electrical activity – and were then randomly assigned to receive either standard care alone or standard care plus metformin.

Standard care included lifestyle education focused on physical activity, nutrition, sleep, and management of comorbidities. Participants in the metformin group received the medication in addition to these measures.

Key findings: Fewer AFib episodes with metformin

Over the 12 months following ablation, the analysis revealed:

• 78% of those taking metformin experienced no AFib episodes lasting 30 seconds or longer, compared with 58% of those receiving usual care.
  
• 6% of participants in the metformin group required a repeat ablation or electric cardioversion (a procedure to restore normal rhythm) versus 16% in the usual care group.
  
• 8% of participants in the metformin group had recurrent AFib during rhythm monitoring, compared with 16% in the usual care group.
  
• Antiarrhythmic medication was required by 8% of participants in the metformin group versus 18% in usual care.
  
• Weight changes were minimal across both groups, consistent with previous findings that metformin produces little or no weight reduction in people without diabetes.
  

“Treatment with metformin in people with obesity who do not have diabetes and are undergoing AFib ablation seems to lower the likelihood of recurrent AFib or atrial arrhythmias after a single procedure,” Dr Deshmukh said. “While most people tolerated the medication well, a significant number stopped taking it due to side effects or because they felt well and did not want to add another medication to their regimen.”

Could other diabetes medications offer similar benefits?

The findings raise further questions about whether other diabetes or weight management drugs – particularly GLP-1 receptor agonists – may also help prevent AFib recurrence in people with obesity who do not have diabetes.

Obesity is a well-established risk factor for AFib. People living with obesity often experience more frequent or recurrent episodes of the condition following catheter ablation. According to the American Heart Association’s 2025 Heart Disease and Stroke Statistics, more than six million people in the United States currently live with AFib.

“I would suggest conducting a larger study to investigate metformin and other diabetes treatments,” Dr Deshmukh added. “We know that many of these medications offer cardiovascular benefits, and we are starting to gain a better understanding of how they might specifically benefit patients with arrhythmias. A study comparing various medications would be valuable to confirm our findings and also to address questions about tolerability, the feasibility of long-term use, and costs.”

Study design and limitations

The META-AF study was conducted at the University of Michigan between 2021 and 2025. It involved 99 adults with an average age of 63 years; 70% were men, and most were white. Among participants, 70% were classified as obese and the remainder as overweight. About 22% had previously undergone ablation, and 46% experienced AFib that stopped spontaneously within a week.

Participants with Type 1 or Type 2 diabetes were excluded, although 40% met criteria for prediabetes (HbA1c between 5.7% and 6.4%). Individuals taking diabetes medications or those for whom metformin posed risks were also excluded.

All participants received anticoagulant therapy to reduce the risk of stroke. The ablation targeted pulmonary vein tissue, a common source of AFib triggers.

The study was open-label, meaning participants knew which treatment they were receiving. Forty-nine participants were assigned to the metformin group and fifty to standard care. After a three-month healing period post-ablation, and once the metformin dose was gradually increased to its maximum, participants were monitored for recurrent AFib lasting at least 30 seconds. Researchers measured the AFib burden – the proportion of time spent in AFib – at three months and twelve months using clinical monitoring data, handheld devices, pacemakers, and defibrillators.

A notable limitation was participant withdrawal: 12 of the 49 people assigned to metformin discontinued treatment due to side effects or because they felt improved and preferred to stop the medication. The small sample size and single-centre design also limit generalisability to other populations or ablation techniques.

Disclosures and context

The study’s co-authors, funding, and disclosures are listed in the abstract presented at the AHA meeting.

The AHA emphasises that statements and conclusions from conference presentations reflect only the authors’ views and do not necessarily represent official policy or position. Abstracts presented at the Association’s scientific sessions are reviewed for scientific merit but are not peer-reviewed publications. Therefore, these findings are considered preliminary until published in a peer-reviewed journal.

The Association notes that over 85% of its funding derives from non-corporate sources, including individual donations, foundations, estates, investments, and educational material sales. Corporate donations are accepted under strict policies that prevent any influence on scientific content or policy positions.

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Scientists Discover Key Protein Triggering Inflammation Linked to Obesity and Type 2 Diabetes

Key Takeaways:

• Researchers have identified FAM20C as a protein that triggers inflammation and insulin resistance in fat cells, a process linked to type 2 diabetes.
  
• Blocking or removing the FAM20C gene in mice improved insulin sensitivity and reduced inflammation, even without weight loss.
  
• High levels of FAM20C in human fat tissue are associated with insulin resistance, suggesting a potential new therapeutic target.
  
  

Early trigger identified in obesity-related inflammation

Investigators at Weill Cornell Medicine have uncovered an early step in the chain of events that links obesity to inflammation and insulin resistance – key contributors to the development of type 2 diabetes.

Their findings, published on 28 October in the Journal of Clinical Investigation, identify a protein known as FAM20C as a critical “switch” that initiates inflammation within fat cells. The study, conducted in mice, shows that when this protein is removed or blocked, metabolic health improves markedly, even without weight loss.

“By inhibiting or getting rid of FAM20C in fat cells, the mice became healthier even at the same body weight,” said senior author Dr James Lo, the Rohr Family Clinical Scholar and an Associate Professor of Medicine in the Division of Cardiology at Weill Cornell Medicine. “Their fat becomes metabolically healthier, reducing harmful inflammation in fat cells that can lead to chronic diseases like type 2 diabetes, fatty liver disease and heart disease.”

FAM20C: A molecular switch for inflammation

The research team, led by first author Dr Ankit Gilani, a Research Associate in Medicine at Weill Cornell Medicine, discovered FAM20C while screening genes that were switched on in the fat cells of mice with obesity and inflammation. FAM20C belongs to a class of enzymes known as kinases, which work by adding phosphate groups to other proteins – a process that can alter their activity and influence gene expression.

When the researchers increased the production of FAM20C in fat cells, the cells began releasing inflammatory molecules and became resistant to insulin. In contrast, blocking or deleting the gene in mice with obesity had the opposite effect – it reduced inflammation, improved insulin sensitivity, and decreased the accumulation of visceral fat (fat surrounding internal organs), even when total body weight remained unchanged.

“During obesity, when this gene is switched on in the adipose tissue, it causes inflammation,” Dr Gilani explained. “It drives the expression of other inflammatory genes, and then it causes insulin resistance, which can lead to type 2 diabetes.”

Evidence from human fat tissue

To determine whether the same mechanism operates in humans, the researchers analysed visceral fat tissue samples from individuals living with obesity. They found that higher levels of FAM20C were associated with insulin resistance – a key driver of type 2 diabetes – while people with lower FAM20C levels tended to exhibit better metabolic health despite having overweight or obesity.

These findings suggest that the FAM20C pathway could play a pivotal role in determining whether fat tissue becomes inflamed and metabolically harmful or remains relatively benign.

Next Steps: Targeting FAM20C and its downstream pathways

The research team now plans to investigate how FAM20C influences other tissues involved in metabolism and metabolic disease. They are particularly interested in a protein called CNPY4, which is activated by FAM20C and appears to be central to the inflammatory process.

“CNPY4 is going to be a major focus of future research to see how strongly it affects insulin resistance, and whether it could be a target for therapies to treat or prevent insulin resistance,” said Dr Lo, who is also a member of the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine, and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Ultimately, the team hopes to develop small-molecule drugs that can block FAM20C or CNPY4 activity. Such therapies could reduce inflammation, lower visceral fat levels, improve insulin sensitivity, and help prevent or treat type 2 diabetes. Dr Lo noted that these treatments might one day be used alongside weight loss medications, or to support people who continue to experience metabolic inflammation and cardiovascular risk even after losing weight.

Funding and support

This research was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH), through grants R01DK121140 and R01DK121844.

CCH insights

For a long time now we have known that inflammation in visceral adipose tissue is a major factor in insulin resistance, but it is still unknown why some people with obesity experience this adipose tissue inflammation and subsequent metabolic dysfunction, while other people with obesity do not. This research suggests that the FAM20C protein may contribute to this switch from healthy adipose tissue to inflamed, dysfunctional adipose tissue, and could offer an exciting new therapeutic pathway for type 2 diabetes and other cardiometabolic conditions.

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Weight Training Outperforms Running in Blood Sugar Control, Virginia Tech Mice Study Shows

Key Takeaways:

• Researchers at Virginia Tech found that resistance training was more effective than running in improving glucose tolerance and reducing insulin resistance in mice fed a high-fat diet.
  
• Both endurance and resistance exercise reduced body fat and improved blood sugar regulation, but resistance training yielded stronger metabolic benefits.
  
• The study suggests that strength training could play a particularly valuable role in preventing and managing Type 2 diabetes.
  
  

Weightlifting may offer unique metabolic benefits

Running is widely recognised for its cardiovascular and calorie-burning benefits, but new preclinical findings from the Fralin Biomedical Research Institute at Virginia Tech Carilion suggest that lifting weights may be even more effective for controlling blood sugar and reducing body fat.

Published on 30 October in the Journal of Sport and Health Science, the study compared the effects of endurance and resistance exercise in mice fed a high-fat diet, a common experimental model for obesity, hyperglycaemia, and Type 2 diabetes.

The team, led by Professor Zhen Yan, an exercise medicine researcher and director of the institute’s Centre for Exercise Medicine Research, found that while both running and weight training improved the body’s ability to clear excess glucose from the bloodstream, resistance training had a stronger impact on reducing both subcutaneous and visceral fat, improving glucose tolerance, and lowering insulin resistance.

“We all want to live a long, healthy life,” said Yan. “We all know the benefits of regular exercise. There is plenty of evidence in humans that both endurance exercise, such as running, and resistance exercise, such as weightlifting, are effective in promoting insulin sensitivity.”

Although both types of activity are known to improve metabolic function, the researchers noted that there had previously been no rigorous, controlled comparison between them.

Developing a model for ‘mouse weightlifting’

To address this gap, the Virginia Tech team created a first-of-its-kind preclinical model of resistance training in mice.

In their experiment, the mice lived in custom-built cages where food was available only through a hinged, weighted lid. To eat, the mice had to lift the lid while wearing a small shoulder collar, performing a movement similar to a human squat. The load was gradually increased over time, effectively replicating progressive strength training.

Meanwhile, the endurance group of mice was given unrestricted access to a running wheel, a standard model for voluntary aerobic exercise. Control groups included sedentary mice maintained on either a normal or high-fat diet.

Over an eight-week period, the researchers monitored changes in body weight, fat distribution, and body composition. They measured exercise capacity with treadmill tests, assessed cardiovascular and muscular performance, and evaluated blood sugar regulation. Muscle tissue samples were also analysed to study insulin signalling at the molecular level.

Using their novel resistance training model, the team could directly compare the metabolic outcomes of running and strength exercise under controlled conditions.

“Our data showed that both running and weightlifting reduce fat in the abdomen and under the skin and improve blood glucose maintenance with better insulin signalling in skeletal muscle,” Yan said. “Importantly, weightlifting outperforms running in these health benefits.”

Implications for obesity and diabetes prevention

Obesity and Type 2 diabetes remain among the most pressing public health challenges, driven largely by high-fat diets and sedentary lifestyles. The new study supports existing clinical evidence showing that endurance, resistance, and high-intensity interval training all contribute to better long-term blood sugar control, reduced body mass index, lower blood pressure, and improved overall well-being.

However, this Virginia Tech study fills a critical gap by directly comparing the two types of exercise in a controlled model of diet-induced obesity. The findings may have important implications for exercise recommendations and diabetes prevention strategies.

“The findings also bring good news for people who, for any number of reasons, cannot engage in endurance-type exercise,” Yan explained. “Weight training has equal, if not better, anti-diabetes benefits.”

Exploring new mechanisms and future therapies

The researchers also observed molecular changes in skeletal muscle that may help explain the enhanced benefits of resistance training. These shifts in insulin signalling pathways could, according to the team, inform the development of new drug therapies for managing Type 2 diabetes.

Interestingly, the improvements seen with resistance training were not directly linked to increased muscle mass or superior exercise performance, suggesting that unique metabolic mechanisms may be at work.

Yan emphasised that although pharmacological interventions such as GLP-1 receptor agonists are valuable tools in diabetes management and weight loss, they cannot replace the broad, systemic benefits of physical activity.

“The take-home message is that you should do both endurance and resistance exercise, if possible, to get the most health benefit,” he said.

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and by the Red Gates Foundation, with collaborators from the University of Virginia contributing to the work.

CCH insights

This is an interesting study, but it is important to note it was conducted in mice, not humans. Having said that, perhaps the most reassuring thing about these results is that both types of exercise provided metabolic health benefits. The critical thing about physical activity is that any amount and type is better than doing none, and while a combination of endurance and resistance is probably best, if you can only manage one type or the other, it will have a positive impact.

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