Category: Metabolic Disorders

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Women with Type 2 Diabetes More Likely to Develop Mental Health Conditions

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Men, on the other hand, experience more cardiovascular and renal disease post-diagnosis

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In the years following type 2 diabetes diagnosis, women are more likely to develop mental health conditions, while men are more likely to develop cardiovascular and renal complications, according to a study published August 25th in the open access journal PLOS Medicine by Fabiola Eto from Queen Mary University of London, UK, and colleagues.

Type 2 diabetes, a metabolic disorder defined by high blood sugar, results from resistance to or insufficient production of insulin. Globally, type 2 diabetes affects about 536.6 million people between 20 and 79 years old, or 10.5% of the population; by 2045, this number is expected to rise to 700 million. Cardiovascular disease, end-stage renal disease, and mental health disorders like depression and anxiety are all associated with type 2 diabetes. Women and men are known to experience these conditions differently, but research has not yet described the disease trajectories according to sex and age in people with type 2 diabetes.

Eto and colleagues examined anonymized health records from 28,720 men and women in the UK who developed type 2 diabetes between 2010 and 2020. Men constituted 62% of the cohort with a median age of 54 at type 2 diabetes onset; women were on average older at diagnosis.

In the years following diagnosis, 39% of the participants experienced at least one significant health event. The events’ trajectory and timing differed by sex. For example: women were more likely to develop mental health conditions post-diagnosis (8.1% compared to 5.3%) and to experience trajectories culminating in death, while men showed higher proportions of cardiovascular disease (8.4% compared to 5.3%), end-stage renal disease, and hypertension (21.1% compared to 20.2%). The researchers noted that on average, women used more health services and long-term prescriptions than men, which may contribute to the increased diagnoses.

There were several similarities between the sexes as well. Both women and men who had a combination of type 2 diabetes and a mental health condition experienced premature mortality compared to other trajectories. Across all age groups and sexes, hypertension was the most frequent event following type 2 diabetes.

Current UK medical guidelines lack sex-specific prevention strategies and management for type 2 diabetes and comorbidities, especially mental health conditions. This study highlights the need for healthcare interventions differentiated by characteristics like sex and age.

The authors add, “One of the clearest signals in our data was the sex difference. Younger women with type 2 diabetes were showing mental health complications earlier and more often than we expected, which suggests routine psychological screening should be incorporated into standard diabetes care. For men, the pattern looked different: cardiovascular and kidney risks tended to emerge earlier, pointing to a need for earlier monitoring and stronger strategies to support men’s engagement with their treatment over time.”

Provided by PLOS

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GLP-1s do not Cause Major Psychiatric Harm, Review Shows

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There is no link between the widely used diabetes and obesity medications known as GLP-1 receptor agonists and increased suicidal thoughts, depression or other serious psychiatric harm based on an integrative review of current scientific evidence conducted by researchers at New Mexico State University and the University of Nevada, Las Vegas.

The review, published in the journal Diabetology, traced the earliest concerns raised over GLP-1 RA therapies and found that after subsequent investigations, the medications do not increase psychiatric risk.

“GLP-1 RAs have become a cornerstone treatment for Type 2 diabetes and obesity, now used by tens of millions of patients worldwide,” said Jagdish Khubchandani, a professor of public health at NMSU, who co-authored the study with Kavita Batra, executive director of medical research and scholarly activities at the UNLV Kirk Kirkorian School of Medicine.

Reports that GLP-1s might trigger suicidal ideation, depression or anxiety began appearing  soon after the medications gained mainstream popularity. Those reports then prompted formal safety reviews by the U.S. Food and Drug Administration and the European Medicines Agency, beginning in 2023.

The research team analyzed five years of mechanistic, pharmacovigilance, observational and regulatory evidence to trace how early reports were investigated and how the scientific and regulatory consensus shifted over time. Earlier this year, the FDA removed its suicidality warning from GLP-1 medications.

“When reports of depression and suicidal thoughts first surfaced with GLP-1 RA use, they came from patients and doctors voluntarily reporting what they saw, and such reports can raise a question, but can’t answer it,” Batra said. “Since then, studies following millions of patients, including a pooled analysis of 91 clinical trials, have found no increase in psychiatric risk. But an answer for millions isn’t an answer for everyone. The right response is to screen and check in with each patient, not to take an effective treatment off the table.”

The review found that early warning signals were largely tied to one drug from selected patient groups, while larger controlled studies often pointed in contradictory directions – something the research team attributes to study design rather than the drugs themselves.

Khubchandani said spontaneous adverse-event reports can be skewed by media attention, by the fact that people with obesity and diabetes already have higher baseline rates of depression and suicidality, and by more frequent medical visits among treated patients that create more opportunities for symptoms to be reported. Controlled studies that account for these factors do not show exceptionally high risks, he added.

Still, the review found that some groups using GL-P1s may need closer monitoring. Patients already taking antidepressants or benzodiazepines showed a substantially amplified reporting signal for suicidal ideation, suggesting that any residual risk may be concentrated among those with pre-existing psychiatric vulnerability rather than the general patient population.

“Depression is more common in people with Type 2 diabetes than in the general population, and it works in both directions: Depression makes diabetes harder to manage, and diabetes makes depression more likely,” Batra said. “So, the mood symptoms a patient reports on any diabetes medication may have been there long before the prescription. That’s exactly why asking about mental health should be a routine part of diabetes care, not a special step reserved for when a drug is under suspicion.”

Khubchandani said the pace of research on GL-P1 medications needs to catch up with their pace of usage, particularly among groups like adolescents, those with serious mental illnesses and other groups underrepresented in clinical trials to date.

 “Just like for several other medications, the decision to use GLP-1 RA should include individualized screening of patients for psychiatric history and suicidality before starting treatment, watching more closely for patients with a history of mood disorders or concurrent psychiatric medication use, and educating patients and caregivers to report mood changes promptly,” Khubchandani said.

To read the review, visit https://www.mdpi.com/2673-4540/7/8/144.

Source: New Mexico State University

Categories : Diet and Nutrition Metabolic DisordersTags :

Keto Diet Delivers Added Liver Benefits Beyond Weight Loss

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WashU Medicine researchers led a clinical trial testing three diets with different proportions of carbohydrates, fats and proteins and found all of them improved metabolic health, but a very low-carb ketogenic diet had additional benefits for liver health and blood sugar control. Credit: Katie Gertler/WashU Medicine

There is no shortage of popular diets to try, and they can generally produce weight loss if followed to the letter. But are all diet plans created equal in terms of reducing the cardiometabolic risks that come with obesity, such as Type 2 diabetes and liver disease?

A randomised clinical trial from Washington University School of Medicine in St. Louis suggests they aren’t, even when they lead to identical amounts of weight loss. Comparing three commonly recommended diet plans, the researchers found that losing weight on any of them improved overall metabolic health in adults with obesity who also had elevated blood sugar and excess fat in their liver – which are important risk factors for developing diabetes. But limiting carbohydrates through a ketogenic diet offered additional benefits for liver health and blood sugar control.

The findings appear August 27 in Cell Metabolism.

“For patients with obesity, prediabetes and fatty liver disease, weight loss induced by a very low-carbohydrate diet provides additional therapeutic effects on glucose and lipid metabolism that should further help prevent the progression to more severe metabolic diseases than weight loss alone,” said Samuel Klein, MD, the Danforth Professor of Medicine and Nutritional Science at WashU Medicine and the study’s senior author. “But all three diets – despite vastly different macronutrient makeups, from very low carbohydrates to very high carbohydrates – successfully improved metabolic health through weight loss alone.”

Which diet best improves metabolic and liver health?

Obesity affects roughly four in 10 Americans, most of whom also face metabolic health risks, including insulin resistance, which leads to prediabetes, and fat buildup in the liver. If left untreated, these problems can progress to Type 2 diabetes, chronic liver disease and cardiovascular events, among other irreversible conditions. While weight loss is the gold standard for reducing obesity-related health risks, it hasn’t been clear which type of diet, in terms of its protein, fat and carb content, works best to improve metabolic health.

To explore that question, the researchers, including first author Max C. Petersen, MD, PhD, an assistant professor of medicine in the John T. Milliken Department of Medicine at WashU Medicine, and Gordon I. Smith, PhD, an associate professor of medicine in the department, randomly assigned 55 adults with metabolically unhealthy obesity – meaning obesity with prediabetes and fatty liver – to follow one of three diets for around five months: a low-carbohydrate, high-fat ketogenic diet; a high-carbohydrate, low-fat, plant-forward diet; or a Mediterranean diet balanced between the two. Participants received 100% of their food throughout the study and attended weekly meetings with a study dietitian to support adherence to the assigned diet.

Across all three groups, participants lost an equal amount of weight, shedding about 10% of their total starting weight, and boosted insulin sensitivity in muscle cells by roughly 50% from baseline. The comparable restoration of insulin sensitivity across diet groups suggests that the weight loss itself was the important factor in combatting muscle insulin resistance – not the combination of fat and carbohydrates used to get there.

“Many metabolically unhealthy patients also are candidates for GLP-1 medicines, which have been very useful tools for helping people lose weight. But our results show that choice of diet remains important because it has an impact on specific health outcomes that go beyond weight loss alone.”

Max C. Petersen, MD, PhD, WashU Medicine

But this wasn’t the case for liver health. The researchers found that sensitivity to insulin in liver cells – which regulates how well the liver suppresses glucose production – improved two to three times more on the ketogenic diet compared with the other diets, though all three groups saw improvement. They also found that the ketogenic diet reduced fat inside the liver by 67% compared to 45% for the other two diets after five months.

“Fatty liver disease affects about 75% of adults with obesity worldwide and has become the fastest-growing cause of chronic liver disease and liver cirrhosis,” said Petersen. “Our study shows that for people with obesity and fatty liver disease, a low-carbohydrate ketogenic diet could help reduce that statistic.”

The ketogenic diet also provided greater improvements in blood sugar control than the other plans did, lowering 24-hour blood glucose measurements by 20% from baseline compared to 8% on the other diets. Insulin levels in the blood throughout the day also decreased by 74% on the low-carbohydrate diet compared to 44% and 27% on the Mediterranean and high-carbohydrate diets, respectively. This sharp decline in insulin reflects the decreased need for insulin to regulate blood glucose when consuming a very-low carbohydrate diet, so the pancreas doesn’t need to overproduce insulin to get a response.

Half of the participants on the low-carbohydrate diet reversed their prediabetes, compared to 29% of participants on the Mediterranean diet and 7% on the high-carbohydrate diet.

“Weight loss – even just a moderate amount – is universally beneficial in people who are metabolically unhealthy,” said Petersen. “Many metabolically unhealthy patients also are candidates for GLP-1 medicines, which have been very useful tools for helping people lose weight. But our results show that choice of diet remains important because it has an impact on specific health outcomes that go beyond weight loss alone.”

In future studies, the researchers are interested in understanding the fundamental mechanisms responsible for the metabolic benefits of weight loss, including the effects of GLP-1 medicines.

Abeeha Shamshad contributed to this story.

Source: University of Washington Medicine

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Scientists Are Discovering Something Surprising About Obesity in Teenagers

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Adolescent metabolism may remain flexible enough for early weight loss interventions to prevent lasting health damage

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Obesity doesn’t look the same at age 15 as it does at age 45 and Duke University School of Medicine researchers are learning why.

A study published in the Journal of Clinical Investigation showed teenagers retain a degree of metabolic flexibility that’s largely lost in adulthood. The study suggests that the way teenage bodies respond to excess weight is fundamentally different and potentially more reversible.

By showing that obesity’s biology changes with age, the discovery points to a potential window when the metabolic damage linked to obesity can be halted, or even reversed, before it becomes a lasting health burden.

“For a long time, medicine has tended to treat adolescents as little adults,” said John Rawls, PhD, a professor of molecular genetics and microbiology and member of the Duke Microbiome Center. “But teenagers are still growing, building muscle and bone, and using energy in ways that are very different from adults. We wanted to understand how those differences shape obesity.”

Nearly 1 in 5 U.S. children has obesity, a condition associated with higher risk for heart disease, diabetes, asthma, and some cancers later in life.

Without intervention, most children with obesity will continue to have obesity into adulthood, said study co-author Sarah Armstrong, MD, a pediatrician and medical weight management specialist at Duke Health.

The change from adolescence to adults happens in late teens to early 20s for women and early-to-mid 20s for men.

But researchers are increasingly asking when those risks become biologically embedded and whether adolescence offers a chance to change course.

The microbiome tells a different story in teens

The Duke team focused on two systems often linked to obesity: the gut microbiome which is the community of microbes living in the digestive tract, and the metabolome, the collection of chemicals produced as the body and microbiome process food and energy.

First, using gut microbes collected from 287 teenagers in the Pediatric Obesity Microbiome and Metabolism Study, they confirmed that teens with obesity have microbiomes that differ compositionally from those of teens at a healthy weight.

Next, Jessica McCann, PhD, a senior research associate in molecular genetics and microbiology, transplanted microbiome samples from adolescents with and without obesity into germ-free mice.

Unlike what researchers often see in adult obesity studies, the mice did not gain extra weight after receiving microbiota from adolescents with obesity.

The findings indicate that while obesity-related differences in the microbiome are beginning to emerge during adolescence, those microbes may not be driving disease the waythey do in adults.

“This suggests there’s a developmental window in which the microbiome becomes involved in obesity,” McCann said. “The relationship between the host and the microbiome may still be developing during adolescence, which means there may be an opportunity to change its trajectory.”

Warning signs appear, but so does resilience

Working in collaboration with the Duke Molecular Physiology Institute, the research team also found differences in how adolescents process nutrients. Adults with obesity often have elevated levels of branched-chain amino acids, as well as related compounds called branched-chain keto acids (BCKA), which are linked with insulin resistance and Type 2 diabetes.

The adolescents showed a different pattern. While branched-chain amino acids were elevated, BCKA levels remained relatively low.

The warning signs are there, McCann said, but teens’ bodies still appear capable of adapting to the metabolic strain of excess weight. “The metabolome is showing early signs of disease progression, but it’s also showing evidence of adaptive plasticity.”

At this stage they may be more responsive to weight management through diet, medication or microbiome-based therapies.

“The evidence increasingly supports intervening as early as possible,” said Armstrong, a professor of pediatrics at Duke.

Researchers hope the work would eventually lead to more personalised obesity treatments, using a child’s microbiome or metabolic profile, to help determine which weight loss therapies are most likely to succeed.

The study was supported by the American Heart Association and the National Institute of Diabetes and Digestive and Kidney Diseases.  

Source: Duke University School of Medicine

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Study Indicates Type 2 Diabetes Operates Differently Across Weight Profiles

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Research published in Diabetologia by Amsterdam UMC and the University of Ghana reveals that type 2 diabetes manifests in two fundamentally different ways depending on a patient’s body mass index (BMI). While type 2 diabetes in patients with a higher BMI is primarily driven by insulin resistance, the study demonstrates that in individuals within a lower BMI range, the condition is caused by the pancreas failing to produce sufficient insulin. Despite these opposing biological mechanisms, medical professionals currently treat both groups with the exact same medications.

Type 2 diabetes is generally seen as a disease associated with being overweight. In wealthy countries that picture holds true: nine out of ten people with type 2 diabetes are overweight. In Africa the situation is different. Almost four in ten African adults with type 2 diabetes are lean, with a normal or even low body weight. In some rural areas, such as in Ghana, it is as many as six in ten. First Author Sabrina Esmail: “This means that there are an estimated ten million lean patients on the African continent who do not fit the standard picture. For them, the problem is therefore a shortage of insulin, not a reduced response to insulin.” Projectleader Charles Agyemang at Amsterdam UMC believes “this study shows that we need to look for better treatments for this large group of lean Africans.”

A different disease process, so a different treatment too

Yet in Africa both groups are almost always given the same treatment, based on international guidelines: oral tablets such as metformin or sulfonylureas. These medicines, however, are mainly effective against insulin resistance, not against a shortage of insulin. They are therefore probably receiving the wrong treatment, and until now the consequences of this had not been investigated. 

The researchers analysed data from more than 3300 African adults with type 2 diabetes from Ghana, Nigeria, Kenya and Europe. “From this we concluded that lean patients more often develop eye damage, known as retinopathy, and strokes. People who are overweight, by contrast, more often have high blood pressure and an increased risk of cardiovascular disease. Chronic kidney disease occurred equally often in both groups,” says senior author Felix Chilunga. The amount of body fat explained the greater part of these differences, which points to genuinely different disease processes. The risk factors differ as well: whereas being overweight is often linked to an unhealthy lifestyle, lean patients have more often experienced malnutrition or a low birth weight, which can disrupt the development of the pancreas.

Type 2 diabetes in lean Africans is therefore, biologically and clinically, a different type of disease from the one seen in people who are overweight. But it is still being treated as though it were the same. As a result, millions of people may not be receiving the right care. Chilunga: “We are calling for targeted clinical trials to determine which treatment works best for this large and often overlooked group of patients.”

Africans in Europe

For Africans in Europe, too, it is very likely that a different treatment is needed. Another study with analysis from data from the UK Biobank showed that people of African descent with a BMI of 26 already have the same diabetes risk as Europeans with a BMI of 30. Studies of migrants in Europe consistently show that Africans are more likely to have type 2 diabetes, develop it around ten years earlier, and have poorer blood sugar control than the native population. Agyemang: “So a considerable proportion of African patients in Europe have a lower BMI but are treated according to guidelines written for the form of the disease found in people who are overweight, and their control is demonstrably worse. There is no reason to assume that the treatment mismatch we describe stops at the border.”

This study was carried out by Amsterdam UMC, University of Ghana, the national Institutes of Health (Center for Research on Genomics and Global Health) via de cohorts AADM and RODAM. The findings were published today in Diabetologia.

Source: Amsterdam UMC

Categories : Metabolic DisordersTags :

A Promising New Obesity and Diabetes Treatment Helps Burn Fat While Keeping Muscle

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Over the past five years, medications called GLP-1s have revolutionised the treatment of metabolic disorders like obesity, diabetes and fatty liver diseases. These drugs are highly effective at helping people lose weight and manage their blood sugar levels.

However, they do come with some risks. Some people taking GLP-1s experience nausea and other gastrointestinal side effects that can be difficult to manage. And, by suppressing appetite and reducing food intake, they have the potential to cause nutritional deficiencies and muscle loss, which can lead to frailty and other problems long term. 

At UC Berkeley, researchers have found a new potential treatment for obesity and diabetes that works by increasing energy expenditure – boosting the body’s metabolic rate – rather than limiting energy intake. 

In a study published online in the journal Science Advances, the researchers show that a molecular compound called 5-tetradecyloxy-2-furoic acid (TOFA) is able to block the production of lipids like cholesterol and triglycerides while simultaneously turning up genes that help cells burn fat and generate energy.

In experiments in mice, the researchers found that TOFA is effective at improving insulin sensitivity and glucose control, lowering triglycerides and improving features of fatty liver disease. When obese mice took the compound, they lost weight from fat but experienced no significant loss of lean muscle mass.

“Body weight responds to two levers: taking in fewer calories, or spending more energy,” said Anders Näär, a professor of metabolic biology and nutrition at UC Berkeley and senior author of the study. “GLP-1s work almost entirely on the first, so we went after the second.”

TOFA was first discovered in the 1970s and is known for being part of a class of compounds called ACC inhibitors, which help block the production of lipids in the body. Though several ACC inhibitors reached mid-stage clinical testing, none has been approved for metabolic disease. This is largely because many of these compounds can also raise triglycerides, posing a significant risk to heart health. 

In the new study, the researchers found that TOFA doesn’t just act as an ACC inhibitor, but also activates PPARα and PPARδ, cellular receptors which turn on genes that let cells take up fat and burn it for energy. In mice, this caused the cells to burn up to 18% more energy with no change in physical activity or increase in body temperature. Perhaps because of this dual mechanism, TOFA also did not raise triglycerides like other ACC inhibitors. 

“TOFA appears to engage a coordinated metabolic response,” said study first author Justin Y. Lee, a postdoctoral student at UCSF who conducted the research as a Ph.D. student at Berkeley. “It is not simply blocking lipid synthesis. It is also activating energy expenditure pathways that may help the body handle excess lipid and glucose more effectively.”

When the researchers tried giving mice two separate compounds – one to block lipid production and a second to boost energy expenditure – they found that the combination was not as effective at improving overall metabolic health as TOFA alone. 

The researchers also explored whether TOFA could be used together with GLP-1 medications like semaglutide, which is sold under the brand names Ozempic or Wegovy, and tirzepatide, which is sold as Mounjaro and Zepbound. In mice, they found that combining TOFA with these GLP-1 drugs led to greater improvements in body weight, glucose control, insulin levels and triglycerides than either treatment alone. 

“In our combination experiments, TOFA worked additively or synergistically with the GLP-1 appetite suppressing drugs, so we view it as complementary rather than as a replacement,” Näär said. 

The researchers caution that TOFA has only been studied in animals, and its safety and efficacy in humans has yet to be tested. With support from Berkeley’s life sciences entrepreneurship ecosystem, including Nucleate and Berkeley SkyDeck, they have founded a new company ReRx Therapeutics to help carry this work to patients. 

Source: UC Berkeley

Categories : Ageing Metabolic DisordersTags :

Waist Circumference Raises Mortality Risk in Elderly – Regardless of BMI

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In a Journal of the American Geriatrics Society analysis of nationally representative data from 6905 US adults aged 65 or older followed between 2011–2024, higher body mass index (BMI) was associated with lower mortality risk, whereas higher waist circumference, a marker of abdominal obesity, was independently associated with higher mortality risk after accounting for BMI.

Compared with normal weight, overweight males and males with class I and II obesity (BMI of 30 to less than 40 kg/m2) had 46% and 51% lower risks of mortality, respectively. Additionally, a high waist circumference was also associated with a 24% higher mortality risk in males. Similar patterns were observed in females.

When BMI and waist circumference were evaluated together, being overweight was associated with lower mortality risk regardless of waist circumference among males. Class I and II obesity also remined associated with lower mortality risk exclusively among males with elevated waist circumference. In contrast, being underweight, regardless of waist circumference, and having normal BMI with elevated waist circumference were both associated with higher mortality risk in both males and females.

“BMI and waist circumference provide complementary information about health risk in older adults,” said study co-author, Bryan Blissmer, PhD, of the University of Rhode Island. “Our findings suggest that considering both measures together, rather than relying on BMI alone, may improve mortality risk assessment and support more informed clinical decision-making.”

Source: Wiley

Categories : Metabolic DisordersTags :

New Obesity Definitions Better than BMI in Revealing Ill Health

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Sleeve gastrectomy. Credit: Scientific Animations CC4.0

An international study led by King’s College London has found that proposed new obesity definitions give greater insight into the ill health of metabolic bariatric surgery candidates compared with Body Mass Index (BMI).

The study, published in Jama Open Network, found that people considered for metabolic bariatric surgery had marked variation in disease burden – the number and severity of diseases – and operation-related risks, despite having similar BMI.

However, by reviewing clinical data from thousands of bariatric surgery candidates and applying new obesity definitions, the researchers were able to better understand their underlying health – which could have important implications for patient treatment and surgery prioritisation in the future.

Led by Professor Francesco Rubino, Chair of Metabolic and Bariatric Surgery at King’s College London, the researchers reviewed retrospective clinical data from 2,316 surgical candidates across four specialist centres – King’s College Hospital in the UK, and centres in France, Spain and Brazil.

They applied the new obesity definitions: clinical obesity, where there is clear evidence that excess fat, or adiposity, is causing organ damage, and preclinical obesity, where organ function is preserved despite excess adiposity.

From the surgical candidates, 73.8% had clinical obesity and 26.2% had preclinical obesity. Despite both groups of patients having similar BMI, patients with clinical obesity had far greater surgery-related and cardiovascular risks. They also had an overall high chance of death.

These findings suggest that distinguishing between clinical and preclinical obesity reveals key information about the health status and risks to surgery candidates that BMI alone cannot capture.

This study shows that the distinction between clinical and pre-clinical obesity is clinically meaningful even among surgical candidates with very high BMI levels, because BMI alone cannot tell us who has active disease.”Professor Francesco Rubino, senior author and Chair of Metabolic and Bariatric Surgery at King’s College London

He continued: “It is now essential that future surgical studies and registries systematically report patients’ clinical or pre-clinical obesity status, so that surgical safety, effectiveness and cost-effectiveness can be interpreted in the appropriate clinical context.”

Traditionally, obesity has been classified primarily using BMI, a measure of weight relative to height that provides limited information about whether excess fat is actually affecting a person’s health. BMI levels have historically played a central role in determining eligibility and priority for metabolic bariatric surgery – operations of the stomach that help people lose weight and fix health issues, such as type 2 diabetes.

In 2025, the Lancet Diabetes & Endocrinology Commission on Clinical Obesity proposed a new diagnostic framework. This distinguished between clinical obesity, where there is clear evidence that excess fat, or adiposity, is leading to organ dysfunction, from preclinical obesity, where organ function is preserved but future health risk is increased.

In the latest study, the researchers found that these differences in disease status were not reflected in BMI. In the UK centre, for example, BMI was roughly 47.5 among patients with clinical obesity and 48.5 among those with preclinical obesity. Yet those with clinical obesity were approximately 10 years older and had substantially higher risk of death, cardiovascular risk and operation-related risk.

The researchers argue that for patients with clinical obesity, surgery primarily represents treatment of established disease. On the other hand, for those with preclinical obesity, its key goal may instead be to reduce future health risk. Recognising this distinction could help clinicians plan surgery, as well as select and prioritise surgical candidates.

Read the full study here: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2852615

Source: King’s College London

Categories : Metabolic DisordersTags :

Researchers Examine Unanticipated Benefits of GLP-1 Medications

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Editorial highlights emerging benefits and questions surrounding this rapidly expanding class of medications

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GLP-1 receptor agonists and dual agonists have transformed the treatment of obesity and other metabolic diseases, and a new editorial co-authored by Dr Steven Heymsfield of LSU’s Pennington Biomedical Research Center and Dr Adam Gilden of the University of Colorado examines what scientists are learning as these medications reach millions of people.

The editorial, “Unanticipated Effects of GLP-1 Receptor Agonists: A Net Positive,” was published in the journal Obesity and highlights additional benefits that were not fully anticipated when the drugs were initially developed.

“Most of the unanticipated side effects of GLP-1 receptor agonists have been positive,” the authors wrote.

The researchers highlight evidence suggesting GLP-1 medications may reduce inflammation and lower the risk of certain cardiovascular and musculoskeletal conditions. Emerging studies also suggest the medications may reduce alcohol consumption and the risk of certain substance use disorders, although additional clinical trials are needed to confirm these effects.

At the same time, questions remain about the medications’ effects on lean body mass and nutritional health. Weight loss associated with GLP-1 medications can include reductions in lean mass, including muscle, making it important to understand how to preserve muscle through exercise and appropriate nutrition. Reduced appetite may also increase the risk of micronutrient deficiencies in some patients.

“GLP-1 receptor agonists have already transformed the practice of medicine in the United States, and this change will continue as more medications come onto the market,” the authors wrote.

The researchers identify three key priorities for future GLP-1 research:

  • Understanding the mechanisms behind potential reductions in inflammation,
  • Conducting randomised trials to better understand changes in lean body mass and ways to preserve muscle,
  • Conducting larger randomised trials to determine whether these medications can reduce alcohol use disorders.

Despite the remaining questions, the authors conclude that the evidence available to date supports a favourable overall risk-benefit profile for GLP-1 receptor agonists and dual agonists.

Source: Pennington Biomedical Research Center

Categories : Cardiovascular Disease Metabolic DisordersTags :

GLP-1 Drug Linked to Heart Benefits for High-risk Patients

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Findings from clinical practice will help inform shared decision making

Human heart. Credit: Scientific Animations CC4.0

Adding the GLP-1 receptor agonist drug tirzepatide to standard care for patients with type 2 diabetes and heart disease is associated with a lower risk of a major cardiovascular event, such as a heart attack or stroke, finds a study published by The BMJ today.

Randomised trials and observational studies have shown non-inferior effects of tirzepatide compared to another GLP-1 receptor agonist, dulaglutide, for major adverse cardiovascular events (MACE) – a combined measure of heart attack, stroke, and death from any cause. But evidence on the effects of adding tirzepatide to standard care is more limited, resulting in uncertainty for both regulators and clinicians.

To address this, researchers analysed clinical practice data from two US health insurance claims databases between May 2022 and May 2025. They aimed to estimate the cardiovascular effects of adding tirzepatide to standard care for patients with type 2 diabetes, a body mass index of at least 25, and established heart disease by comparing the outcomes to sitagliptin, another diabetes drug.

Sitagliptin was chosen as a neutral placebo proxy based on several studies showing no effect on cardiovascular outcomes.

The main outcome of interest was a reduction in MACE, which was monitored from the first day of treatment up to one year, or until the individual stopped or switched treatment, or disenrolled from the health plan.

Factors including age, sex, race, body mass index, previous heart problems, other chronic conditions, and medication use were taken into account, and a technique called propensity score overlap weighting was used to balance out differences between the two groups to draw more reliable conclusions.

A total of 52,971 individuals were included in the analysis (average age 70 years; 51% female), of whom 35,353 started tirzepatide and 17,618 started sitagliptin.

At one year, the risk of MACE was 2.9% in the tirzepatide group and 4.4% in the sitagliptin group (a 32% relative reduction), and the researchers estimate that for every 70 patients starting tirzepatide, one case of MACE would be prevented.

For individual MACE components, tirzepatide was associated with a 33% lower risk of heart attack compared with sitagliptin, whereas ischaemic stroke showed no meaningful difference.

Infections requiring hospital admission were also lower with tirzepatide (one admission prevented for every 48 patients), as was infection related death (one death prevented for every 200 patients) and death from any cause (one death prevented for every 122 patients).

This is an observational study, but the researchers previously benchmarked their design, data, and analytics infrastructure against a randomised controlled trial before drawing conclusions about cause and effect.

They also acknowledge several limitations including a relatively short follow-up period, which may underestimate long term cardiovascular and safety effects, possible misclassification of treatment duration or outcomes, and findings may not apply to other healthcare systems or patients without established cardiovascular disease.

However, they conclude: “This study shows how trial-anchored evidence from clinical practice can estimate the expected cardiovascular benefit of initiating tirzepatide beyond standard background treatment and inform shared decision making.”

A linked editorial notes that while this study provides an important, transparent estimate of what initiating tirzepatide might achieve in routine care, it does not establish a mortality indication or define the best sequence for cardiometabolic therapy.

The authors say longer follow-up, randomised and pragmatic comparisons, and more studies of additive benefit on contemporary background treatment are needed. Furthermore, cardiovascular efficacy cannot benefit a population if cost, authorisation barriers, supply, and discontinuation prevent sustained treatment, they add.

As such, they conclude: “The signal is compelling; the causal and clinical placement questions remain open.”

Source: BMJ Group