Tag: semaglutide

Categories : Ageing Metabolic DisordersTags :

Popular GLP-1 Drug May Slow Down Biological Aging

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By calming inflammation and reducing excess fat, semaglutide may postpone several molecular signs of aging, pointing to the potential of GLP‑1 receptor agonists to help prevent age‑related diseases.

Photo by Haberdoedas on Unsplash

Semaglutide slowed biological aging across multiple epigenetic clocks in a randomised, double-blind, placebo-controlled clinical trial. The strongest signals were seen in epigenetic measures linked to inflammation, brain, heart, blood, kidney, liver and metabolic health, suggesting that the drug may influence aging-related biology across multiple body systems. The findings offer early clinical evidence that GLP-1 receptor agonists may influence aging biology.

Glucagon-like peptide-1 (GLP-1) receptor agonist medications have gained widespread attention for effectively treating obesity, lowering blood sugar and decreasing the risk of cardiovascular disease. Some researchers have proposed that these drugs may also influence the biology of aging, but direct evidence in humans has remained limited. Now, a new study provides the first randomised, placebo-controlled clinical evidence that semaglutide, a widely used GLP-1 drug, slows down the accumulation of biological aging markers in the DNA of adults with HIV. The study is published in Nature Communications.

Researchers at the University of California San Diego and several partner institutions analysed data from a previously published clinical trial of 108 adults with HIV‑associated lipohypertrophy, a condition in which excess fat builds up around the abdomen. About half of the participants received weekly injections of semaglutide, with the rest receiving placebo injections.

The team used a set of biological “epigenetic clocks” to track cellular aging over the 32-week treatment period. These clocks detect DNA methylation, chemical marks on DNA that help regulate how genes are turned on or off without changing the genetic sequence itself. By measuring changes in these marks, the team could assess whether the treatment was associated with a slower or faster biological aging pattern.

People with HIV often experience accelerated aging, even if it is well-controlled with antiretroviral therapy, according to first author Michael Corley, PhD, associate professor at UC San Diego School of Medicine and the Stein Institute for Research on Aging. However, the study found compared to the placebo group:

  • Participants treated with semaglutide exhibited a broad pattern of slower biological aging across epigenetic clocks linked to inflammation and blood, brain, heart, kidney, liver and metabolic health.
  • The drug slowed the pace of biological aging by 9 %, as measured by the DunedinPACE epigenetic clock.
  • The drug significantly slowed biological processes associated with the risk of all‑cause mortality and age-related disease, as measured by the PCGrimAge epigenetic clock.

Research suggests there are several mechanisms by which semaglutide may influence biological aging. By reducing inflammation and metabolic stress, GLP-1 drugs decreased chronic immune activation, a primary driver of accelerated aging in people with HIV. They also reduce visceral and ectopic fat that accumulates around the abdomen and organs, which may help curb the inflammatory and metabolic signals that promote aging.

“Emerging data also suggest that GLP-1 drugs may reprogram certain cells in different organs, which could help explain why we see effects across multiple aging clocks,” said Corley.

While the study focused on people with HIV‑associated lipohypertrophy, Corley says it may also offer lessons for the wider population.

“Many of the biological processes we study in HIV are also central to aging in the general population,” he said. “Because these processes can emerge earlier or be more pronounced in people with HIV, this community can help us identify interventions that may improve healthspan more broadly.”

In a related pilot study published in npj Aging, Corley and another team of researchers found that taking semaglutide for 24 weeks:

  • Reduced the rate of biological aging for 42% of participants with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD) as measured by the DunedinPACE epigenetic clock. Those participants also had a greater reduction in liver fat compared with participants whose pace of aging sped up.
  • Slowed aging associated with the risk of all‑cause mortality in 34% of participants as measured by the PCGrimAge epigenetic clock.
  • Increased the length of telomeres in nearly 49 % of participants as measured by the PCDNAmTL epigenetic clock. Those participants also tended to walk faster after treatment, suggesting better physical function.

Together, these studies add to growing evidence that GLP-1 drugs may influence pathways involved in biological aging.

“We are not saying that semaglutide reverses aging or makes people younger. What we are seeing is a signal that it may slow some of the biological processes associated with aging.”

— Michael Corley, PhD

“We are not saying that semaglutide reverses aging or makes people younger,” said Corley. “What we are seeing is a signal that it may slow some of the biological processes associated with aging. With newer GLP-1–based therapies now emerging, the field has an opportunity to test whether different drugs in this class have distinct effects on aging biology and to identify which patients may benefit most.”

Larger clinical trials are needed to confirm the findings, determine how long treatment effects last, and establish optimal dosing and treatment duration for both people with HIV and the broader population. Future studies will also be needed to test whether the effects of GLP-1 effects on aging biology are enhanced when combined with lifestyle interventions such as diet, exercise and sleep optimization.

The Stein Institute for Research on Aging plans to translate these results into individualized “aging dashboards” to track biological aging with epigenetic clocks, enabling clinicians to design personalised therapies that target the underlying mechanisms of aging and help prevent age‑related diseases.

By Susanne Clara Bard

Source: University of California San Diego

Categories : Cancer Metabolic DisordersTags :

GLP-1 Drugs May Also Reduce Risk of Death from Colon Cancer

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Photo by Haberdoedas on Unsplash

A new University of California San Diego study offers compelling evidence that GLP-1 receptor agonists may do more than regulate blood sugar and weight. In an analysis of more than 6800 colon cancer patients across all University of California Health sites, researchers found that those taking glucagon-like peptide-1 (GLP-1) medications were less than half as likely to die within five years compared to those who weren’t on the drugs (15.5% vs 37.1%).

The study, led by Raphael Cuomo, PhD, used real-world clinical data from the University of California Health Data Warehouse to assess outcomes across the state’s academic medical centres. After adjusting for age, body mass index (BMI), disease severity and other health factors, GLP-1 users still showed significantly lower odds of death, suggesting a strong and independent protective effect.

The survival benefit appeared most pronounced in patients with very high BMI (over 35), hinting that GLP-1 drugs may help counteract the inflammatory and metabolic conditions that worsen colon cancer prognosis. Researchers believe several biological mechanisms could explain the link. Beyond regulating blood sugar, GLP-1 receptor agonists reduce systemic inflammation, improve insulin sensitivity and promote weight loss – all factors that can dampen tumour-promoting pathways. Laboratory studies also suggest that GLP-1 drugs may directly prevent cancer cell growth, trigger cancer cell death and reshape the tumour microenvironment. However, the study authors emphasise that more research is needed to confirm these mechanisms and determine whether the survival benefit observed in this real-world analysis represents a direct anti-cancer effect or an indirect result of improved metabolic health.

Cuomo notes that while these results are observational, they underscore an urgent need for clinical trials to test whether GLP-1 drugs can improve cancer survival rates, especially for patients with obesity-related cancers.

The study appeared in Cancer Investigation on November 11, 2025.

Source: University of California – San Diego

Categories : Cardiovascular DiseaseTags :

Semaglutide and Tirzepatide Reduce Heart Failure Risk by More than 40%

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Right side heart failure. Credit: Scientific Animations CC4.0

Treatment with semaglutide or tirzepatide can reduce health risks for patients with heart failure by more than 40%. These finding come from a study by researchers at the Technical University of Munich (TUM). The medication can drastically reduce the risk of being hospitalised for heart failure or dying.

Semaglutide and related medications are widely used to treat diabetes and obesity. Their potential effects beyond weight loss are now being closely studied. Still, professional societies and regulatory authorities have urged caution. With regard to treating heart failure, cardiology societies have noted that the existing evidence base remains limited.

“Together with our colleagues at Harvard Medical School, we have created a solid evidence base for using these weight-loss medications in heart failure,” says Professor Heribert Schunkert, Director of the Department of Cardiovascular Diseases at the TUM University Hospital German Heart Center. “In patients with heart failure with preserved ejection fraction, both drugs have shown a clear protective effect that supports their use. Our analysis of around 100 000 patients provides a robust basis for reassessing an indication expansion and new indication approval in heart failure.“

The study focused on heart failure with preserved ejection fraction or HFpEF, in which the heart’s ability to pump remains intact but the stiffened heart muscle does not fill properly with blood. HFpEF affects more than 30 million people worldwide. To date, there are only a few effective treatment options for this form of the disease.

Large-scale database study provides solid evidence for use in heart failure

Published in JAMA, the study examined the effects of the drugs semaglutide and tirzepatidein patients with this specific form of heart failure. The researchers analysed three national US insurance claims databases. Their models first confirmed findings from earlier trials in patients with obesity or diabetes, then extended the analysis to populations excluded from clinical trials and to additional outcomes, such as hospitalisation for heart failure and mortality.

Treatment with both drugs led to a more than 40% reduction in the risk of hospitalisation for heart failure or death compared with another diabetes drug that had shown no effect on heart failure outcomes in previous studies.

“Currently, HFpEF can be treated with a few drugs only. At the same time, an increasing number of patients suffers from obesity and diabetes, which further worsens outcomes. In Germany, heart failure is the leading cause for hospitalizations and a major driver of health care expenditure. Our study shows that these drugs are highly effective, which expands treatment options and could prevent many hospital admissions,” says Dr Nils Krüger, resident physician at the TUM University Hospital German Heart Center and lead author of the study.

Data-driven approaches to drug approval

The study drew on patient populations nearly 20 times larger than those in traditional clinical trials. This allowed researchers to capture clinical practice and demonstrate that the benefits seen in pivotal trials also apply to broader patient groups. “The future belongs to such data‑driven approaches – alongside traditional trials, they can help ensure that findings from basic research feed into patient care more quickly,” explains Prof Schunkert.

From the researchers’ perspective, such analyses are also becoming increasingly relevant for Germany. The Health Data Utilization Act provides that anonymized health insurance data will in future be made systematically available for such research projects, while strictly protecting sensitive personal data. “We use these large data to investigate the safety and effectiveness of medications in clinical practice,” says Dr Krüger.

Source: Technical University Munich

Categories : Expert Opinion Surgeries & ProceduresTags :

SA Surgeon Breaks Down the Deep Plane Facelift Surge Amid Global Aesthetic Trends

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Professor Chrysis Sofianos

Kris Jenner’s “new face” has everyone talking – and it’s widely speculated to be the result of a deep plane facelift, a procedure now dubbed the gold standard in facial rejuvenation. Let’s not even get into how Khanyi Mbau’s face broke the internet. The demand for natural-looking, sophisticated facial transformations has reached an all-time high, both globally and here in South Africa.

A global weight loss boom, fuelled by miracle diabetes drugs, has led to an unexpected side effect: the ‘O weight loss face’, marked by hollowed cheeks, sagging jowls, and prematurely aged skin. In turn, this phenomenon has sparked a significant rise in demand for advanced facial rejuvenation, and particularly the deep plane facelift – what experts term ‘the facelift that lifts where it matters most’.

“One of the most common complaints I hear from patients is, ‘I finally have the body I wanted, but my face looks 10 years older,’” says Professor Chrysis Sofianos, one of South Africa’s leading plastic surgeons and experts in deep plane facelifts.

The Gauteng-based specialist notes that he has seen a meteoric increase in consultations from patients seeking to reverse the facial deflation and laxity caused by rapid weight loss.

“This is just one instance where the deep plane facelift truly shines, as it restores natural facial harmony by lifting and repositioning deep tissues, not just tightening the skin. By addressing the deeper structural changes caused by significant weight loss, this approach delivers far more natural outcomes and a timeless look.

The Facelift No One Can See

What sets the deep plane facelift apart? Unlike traditional facelifts that only address the skin’s surface, the deep plane technique lifts beneath the superficial musculoaponeurotic system (SMAS) layer of tissue to reposition and support the foundational structures of the face. This approach not only rejuvenates the face more effectively than other techniques, but also avoids the tell-tale ‘pulled’ look, offering a more subtle, organic-looking transformation.

Professor Sofianos further enhances his results with the Vertical Restore method, lifting facial tissues vertically – in harmony with the way gravity naturally impacts the face over time. This technique provides holistic rejuvenation of the midface, jawline, neck, and brow, with results that restore youthful contours and expressions.

“Only a handful of surgeons currently offer this breakthrough procedure, and I can confidently state that the deep plane facelift is the gold standard for natural, long-lasting revitalisation.”

According to Professor Sofianos, deep plane facelifts offer several major advantages compared to conventional facelifts:

  • Superior, long-lasting results: By repositioning deeper facial structures rather than merely tightening the skin, the deep plane facelift offers longer-lasting, more authentic outcomes.
  • Natural look and movement: The technique avoids excessive skin tension, ensuring the face remains expressive and vibrant – even in motion.
  • Comprehensive rejuvenation: From sagging jowls and hollow cheeks to neck laxity, the deep plane facelift addresses multiple problem areas in one single, unified procedure.

The Ultimate One-Stop Shop for Aesthetic Excellence and Care

Professor Sofianos’s practice is not only a leader in surgical innovation but also a complete one-stop destination for all aesthetic needs. His clinic offers a full suite of surgical and non-surgical procedures – from advanced facial surgeries to injectables, laser treatments, skin rejuvenation, and body contouring. Each treatment is bespoke and delivered with meticulous care to ensure natural, balanced, and long-lasting results.

What truly sets Professor Sofianos apart, however, is his absolute commitment to patient care. Every facelift is supported by a holistic pre- and post-operative care programme, designed to optimise recovery and results.

A signature component of this is the integration of hyperbaric oxygen therapy (HBOT), which is included as standard in his facelift packages. HBOT begins around 7–10 days after surgery, dramatically improving oxygen delivery to tissues, speeding up wound healing, reducing bruising and swelling, and significantly shortening overall healing time.

As a result of these additional post-surgical interventions, the typical recovery period is two to three weeks, with most patients able to resume social activities within a month. With comprehensive aftercare – including HBOT and nutrient therapies – patients benefit from accelerated healing and refined results that continue to improve for several months post-surgery.

“The success of a procedure isn’t just about the surgery itself, but about guiding patients through a complete journey from start to finish,” he explains. “My patients receive comprehensive, full-spectrum care – including pre-operative preparation, expert surgical techniques, post-operative hyperbaric therapy, scar management, and continuous follow-ups. It’s this level of commitment that ensures optimal outcomes, supporting patients through every step of their transformation and helping them feel comfortable and secure throughout.”

A Lasting Solution for Facial Rejuvenation in the Weight Loss Era

As weight loss medications continue to help patients address issues with weight management and obesity, experts predict that the demand for facial rejuvenation will only rise.

“This trend has created both challenges and opportunities for plastic surgeons, and in many ways is reshaping our field in real time. The good news for patients is that we’re at the beginning of a new chapter in aesthetic medicine – where a combination of sophisticated surgical techniques and aftercare procedures are helping people achieve what was once thought impossible: natural-looking transformations that truly turn back the clock.”

For those seeking to restore their youthful appearance with confidence and discretion, the deep plane facelift offers an unmatched, cutting-edge solution – delivered with precision, artistry, and unparalleled care by Professor Chrysis Sofianos and his dedicated team.

Categories : Diseases, Syndromes and ConditionsTags :

Semaglutide Treats Liver Disease in Two Thirds of Patients

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Human liver. Credit: NIH

Results from the ESSENCE phase 3 clinical trial published in the New England Journal of Medicine shows that treating patients with semaglutide can halt and even reverse the disease.

The placebo-controlled outcome trial of participants with a life-threatening form of liver disease known as Metabolic dysfunction associated steatohepatitis (MASH) was conducted at 253 clinical sites across 37 countries around the world. This is the first regulatory-level trial showing the benefit of semaglutide for people with MASH.

The trial is led by two Chief Investigators, Professor Philip Newsome at King’s College London and Arun Sanyal at the VCU School of Medicine, United States, and funded by Novo Nordisk.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a long-lasting liver condition caused by having too much fat in the liver. MASH is a more severe form of MASLD. It is closely linked with obesity as well as conditions such as type 2 diabetes and heart and circulatory disease. Over time, the build-up of fat in the liver can lead to inflammation, liver fibrosis, cirrhosis and liver cancer. MASLD affects 1 in 5 people in the UK but there are no medicines licensed to specifically treat the disease.

Researchers chose to investigate semaglutide as a potential treatment because this class of drug helps reduce fat and liver scarring for people with MASH. Previous smaller but positive studies by Professor Newsome, published in the Lancet and NEJM, had shown using semaglutide as a treatment for MASH would have benefit for these patients.

Between May 27, 2021 and April 18, 2023, 800 participants were randomly assigned to receive once-weekly injection of 2.4milligrams of semaglutide or placebo, alongside lifestyle counselling. More than half of participants had type 2 diabetes and approximately three-quarters were living with obesity.

Results from the ESSENCE trials after 72 weeks of treatment found 62.9% of participants experienced a reduction in steatohepatitis (inflammation of the liver with fat accumulation in the liver) versus 34.3% for participants who took the placebo. The results also show 36.8% of the semaglutide group had improvements of their liver fibrosis versus 22.4% in the placebo group. Researchers also found other benefits. Those receiving semaglutide also saw improvements in liver enzymes and other blood measures of liver fibrosis, as well as 10.5% weight loss. Gastrointestinal adverse events were more common in the semaglutide group, such as nausea, diarrhoea, constipation, and vomiting.

I’ve been working with GLP-1 treatments for sixteen years and these results are hugely exciting. MASLD is a growing problem worldwide and this trial will provide real hope for patients with MASH. While these results must be treated with caution, the analysis shows semaglutide can be an effective tool to treat this advanced liver disease.

Professor Philip Newsome, Director of the Roger Williams Institute of Liver Studies

The research team will follow close to 1200 participants from 37 countries for up to five years to gather data on semaglutide’s impact on long-term liver complications.

Source: King’s College London

Categories : Metabolic Disorders OphthalmologyTags :

Study Reveals Association Between Semaglutide Use and Optic Neuropathy

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Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.

Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.

The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.

In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.

“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.

They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.

The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.

The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.

Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”

Categories : Exercise Metabolic DisordersTags :

Metformin’s Weight Loss Tied to “Anti-hunger” Molecule

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A new study finds that the modest weight loss from taking metformin is attributable to an appetite-suppressing molecule that is abundant after exercise

Photo by I Yunmai on Unsplash

An “anti-hunger” molecule produced after vigorous exercise is responsible for the moderate weight loss caused by the diabetes medication metformin, according to a new study in mice and humans. The anti-hunger molecule, lac-phe, was discovered by Stanford Medicine researchers in 2022.

The finding, made jointly by researchers at Stanford Medicine and at Harvard Medical School and published in Nature Metabolism, further cements the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite. It may pave the way to a new class of weight loss drugs.

“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” said Jonathan Long, PhD, an assistant professor of pathology. “Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people.”

Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. Although this amount of weight loss is modest when compared with the 15% or more often seen by people taking semaglutide, the discoveries that led to those drugs also grew from observations of relatively minor, but reproducible, weight loss in people taking first-generation versions of the medications.

Post-workout appetite loss

When Long and colleagues at Baylor University discovered lac-phe in 2022, they were on the hunt for small molecules responsible for curtailing hunger after vigorous exercise. What they found was a mishmash of lactate and an amino acid called phenylalanine. They dubbed the hybrid molecule lac-phe and went on to show that it’s not only more abundant after exercise but it also causes people (as well as mice and even racehorses) to feel less hungry immediately after a hard workout.

“There is an intimate connection between lac-phe production and lactate generation,” Long said. “Once we understood this relationship, we started to think about other aspects of lactate metabolism.”

Metformin was an obvious candidate because as it stimulates the breakdown of glucose (thus reducing blood sugar levels) it can trigger the generation of lactate.

The researchers found that obese laboratory mice given metformin had increased levels of lac-phe in their blood. They ate less than their peers and lost about 2 grams of body weight during the nine-day experiment.

Long and his colleagues also analysed stored blood plasma samples from people with Type 2 diabetes before and 12 weeks after they had begun taking metformin to control their blood sugar. They saw significant increases in the levels of lac-phe in people after metformin compared with their levels before treatment. Finally, 79 participants in a large, multi-ethnic study of atherosclerosis who were also taking metformin had significantly higher levels of lac-phe circulating in their blood than those who were not taking the drug.

“It was nice to confirm our hunch experimentally,” Long said. “The magnitude of effect of metformin on lac-phe production in mice was as great as or greater than what we previously observed with exercise. If you give a mouse metformin at levels comparable to what we prescribe for humans, their lac-phe levels go through the roof and stay high for many hours.”

Further research revealed that lac-phe is produced by intestinal epithelial cells in the animals; blocking the ability of mice to make lac-phe erased the appetite suppression and weight loss previously observed.

Finally, a statistical analysis of the people in the atherosclerosis study who lost weight during the several-year study and follow-up period found a meaningful association between metformin use, lac-phe production and weight loss.

“The fact that metformin and sprint exercise affect your body weight through the same pathway is both weird and interesting,” Long said. “And the involvement of the intestinal epithelial cells suggests a layer of gut-to-brain communication that deserves further exploration. Are there other signals involved?”

Long noted that, while semaglutide drugs are injected into the bloodstream, metformin is an oral drug that is already prescribed to millions of people. “These findings suggest there may be a way to optimize oral medications to affect these hunger and energy balance pathways to control body weight, cholesterol and blood pressure. I think what we’re seeing now is just the beginning of new types of weight loss drugs.”

Source: Stanford Medicine

Categories : Cardiovascular Disease Metabolic DisordersTags :

Semaglutide Cuts CVD Events by 20% in People with Obesity or Overweight but not Diabetes

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By HualinXMN – Own work, CC BY-SA 4.0

In a large, international clinical trial, people with obesity or overweight but not diabetes taking semaglutide for more than three years had a 20% lower risk of cardiovascular disease outcomes and lost an average of 9.4% of their body weight.

Semaglutide, a GLP-1 medication primarily prescribed for people with Type 2 diabetes, is also FDA-approved for weight loss in people with obesity.

These results were shared in a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2023 and the full manuscript was also published in The New England Journal of Medicine.

“This news is very encouraging for people with overweight or obesity because no treatment specifically directed at the management of obesity and overweight in people without Type 1 or Type 2 diabetes has been tested in a randomised trial and been shown to influence cardiovascular outcomes,” said lead study author A. Michael Lincoff, MD.

While prior research has confirmed the benefits of semaglutide in managing blood sugar, decreasing cardiovascular disease events and reducing weight in people with Type 2 diabetes, this study specifically investigated the potential impact of semaglutide on cardiovascular disease in people with overweight or obesity and cardiovascular disease who did not have either Type 1 or Type 2 diabetes.

In this randomised, controlled, double-blind trial, participants were assigned to take either 2.4mg of semaglutide (the FDA-approved semaglutide dose for weight management) or a placebo once a week, which is higher than the FDA-approved semaglutide dose limit for Type 2 diabetes of 2.0mg/week. Each person in the study used a ‘pen’ to inject the medicine or placebo into a skin fold in their stomach, thigh or upper arm each week on the same day, and the dose started at 0.24mg and gradually increased every four weeks up to 2.4mg, and mean follow-up for all participants was 40 months.

In addition to taking either semaglutide or placebo for the trial, all participants also received standard of care treatment for cardiovascular disease, such as cholesterol modifying medications, antiplatelet therapies, beta blockers or other treatments. The authors note that heart disease diagnoses varied among the participants, therefore, treatment was adjusted to meet each individual’s diagnosis and needs, as well as the treatment guidelines in their country of residence.

The study, which ran from October 2018 through June 2023, indicated the following:

  • There was a 20% reduction in the risk of heart attacks, strokes or death due to cardiovascular disease in the participants who took semaglutide, compared to the participants in the placebo group.
  • In the semaglutide group, the participants’ body weight was reduced, on average, by 9.4% compared to a reduction of 0.9% among the adults in the placebo group.
  • There were no new safety concerns found in the study, which researchers note is encouraging since the SELECT trial is the largest and longest (4.5 years) trial of semaglutide in adults without Type 1 or Type 2 diabetes.
  • The number of serious adverse events was lower in the semaglutide group. Previous studies of medications of the GLP-1 receptor agonist class have shown an association with gallbladder disorders, and in SELECT, there was a slightly higher rate of gallbladder disorders in the semaglutide vs placebo group (2.8% vs 2.3%, respectively).
  • Semaglutide was stopped more frequently than placebo for gastrointestinal intolerance, a known side effect of this class of medications; however, there was no higher rate of serious gastrointestinal events.
  • The researchers noted that this medication did not lead to an increased rate of pancreatitis, which has been a concern with prior medications of this type.
  • Of note, other weight-loss medications that are not GLP-1 receptor agonists have been associated with increased risks of psychiatric disorders or cancer; these risks were not elevated with semaglutide in the SELECT trial.

“It’s been estimated that within about ten years, over half of the world’s population will have overweight or obesity,” said Dr Lincoff. “And while GLP-1 medications are frequently prescribed for patients with vascular disease and Type 2 diabetes, there is a significant number of people who do not have Type 1 or Type 2 diabetes but do have vascular disease and overweight or obesity for whom these medications are often not available due to access to care issues, insurance coverage or other factors. This population may now potentially benefit from semaglutide, and importantly, our results indicate the magnitude of cardiovascular risk reduction with semaglutide among people without Type 1 or Type 2 diabetes is the same as what we have seen in people with Type 2 diabetes. Our findings expand the opportunity to treat patients who have overweight or obesity and existing heart disease without Type 1 or Type 2 diabetes, and we have a chance to significantly reduce their risk of a secondary cardiovascular event including death.”

Among the study limitations were including adults with prior cardiovascular disease, thereby not investigating primary prevention of cardiovascular disease (people with no history of a heart attack, stroke and/or peripheral artery disease). In addition, 28% of the study participants were female, which is not proportionate to the number of women with cardiovascular disease and overweight or obesity in the general population.

Additional analyses will include identifying the mediators of the cardiovascular benefit to determine to what extent the results were driven by reduction of metabolically unhealthy body fat, positive impacts on inflammation or blood sugar, direct effects of the medication itself on plaque build-up in the arteries, or a combination of one or more variables.

Source: American Heart Association

Categories : Gastrointestinal Surgeries & ProceduresTags :

Hold the GLP-1 Agonists Before Surgery, New Advice Says

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Photo by Natanael Melchor on Unsplash

Patients taking Glucagon-like peptide-1 (GLP-1) receptor agonists should stop taking them before they have surgery, due to the risk of aspirating while under general anaesthesia. This is the latest advice from the American Society of Anesthesiologists (ASA).

Initially approved by the Food and Drug Administration (FDA) for type 2 diabetes mellitus and cardiovascular risk reduction, GLP-1 agonists have shot up in popularity due to their effectiveness in weight loss. Despite having recent FDA approval, they have been used off-label for this purpose for quite some time.

When it comes to surgery, a number of organisations have recommended to hold these drugs either the day before or day of the procedure. For patients on weekly dosing, it is recommended to hold the dose for a week, the ASA notes.

GLP-1 agonists are associated with adverse gastrointestinal effects such as nausea, vomiting and delayed gastric emptying. The effects on gastric emptying are reported to be reduced with long-term use, most likely through rapid tachyphylaxis at the level of vagal nerve activation. Based on recent anecdotal reports, there are concerns that delayed gastric emptying from GLP-1 agonists can increase the risk of regurgitation and pulmonary aspiration of gastric contents during general anaesthesia and deep sedation. Patient taking GLP-1 agonists are more likely to have increased residual gastric contents as predicted by adverse gastrointestinal symptoms (nausea, vomiting, dyspepsia, abdominal distension).

The use of GLP-1 agonists in paediatrics has primarily been reported for the management of type 2 diabetes mellitus and obesity. The published literature on GLP-1 agonists in paediatrics is predominantly from paediatric patients 10 to 18 years old and concerns are similar to those reported in adults. During the conduct of general anaesthesia/deep sedation, children on GLP-1 agonists have similar gastrointestinal adverse events at a rate similar to adults.

In a review of the literature, the ASA Task Force on Preoperative Fasting found that, beyond a few case reports, there was little evidence for guidance on preoperative management of GLP-1 agonists. Nevertheless, they made recommendations for elective procedures. In the case of urgent or emergent procedures, they suggested treating the patient as ‘full stomach’.

If the patient’s GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, the guidelines urge surgeons to consider consulting an endocrinologist for bridging the antidiabetic therapy in order to avoid hyperglycaemia.

They further recommend that if gastrointestinal symptoms, such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain, are present, surgeons should consider delaying elective procedures. If the patient has no gastrointestinal symptoms and the GLP-1 agonists have been held as advised, the surgical team can carry on as normal.

Source: American Society of Anesthesiologists

Categories : Gastrointestinal Metabolic DisordersTags :

For Weight Loss, the Side Effects of GLP-1 Agonists can be Hard to Stomach

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GLP-1 agonists are being lauded as game-changers in the fight against obesity, but GLP-1 agonist drugs like semaglutide may come with a heightened risk of severe gastrointestinal problems, according to new research published in JAMA.

Designing their study for the side effects rather than the efficacy of the drugs, the researchers found that GLP-1 agonists are associated with an increased risk of serious medical conditions including gastroparesis (stomach paralysis), pancreatitis and bowel obstruction.

While previous studies highlighted some of these risks in patients with diabetes, this study from the University of British Columbia is the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program and fourth year UBC medical student studying the adverse events of commonly prescribed medications. “The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity or just general weight loss. People who are otherwise healthy may be less willing to accept these potentially serious adverse events.”

GLP-1 agonists have exploded in popularity over the past decade as an off-label weight-loss tool, reaching approximately 40 million prescriptions in the US in 2022.

It was only in 2021 that some forms of the medications were approved as a treatment for obesity. However, randomised clinical trials examining the efficacy of the medications for weight loss were not designed to capture rare gastrointestinal events due to their small sample sizes and short follow-up periods.

“There have been anecdotal reports of some patients using these drugs for weight loss and then presenting with repeated episodes of nausea and vomiting secondary to a condition referred to as gastroparesis,” said senior author Dr Mahyar Etminan, an epidemiologist and associate professor in the department of ophthalmology and visual sciences at the UBC faculty of medicine. “But until now, there hasn’t been any data from large epidemiologic studies.”

To help fill this knowledge gap, UBC researchers examined health insurance claim records for approximately 16 million US patients and looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020. They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another antidiabetic drug.

The researchers analysed the records to see how many patients developed one of four gastrointestinal conditions, and compared that rate to patients using another weight-loss drug, bupropion-naltrexone. Compared to bupropion-naltrexone, GLP-1 agonists were associated with a:

  • 9.09 times higher risk of pancreatitis, which can cause severe abdominal pain and, in some cases, require hospitalisation and surgery.
  • 4.22 times higher risk of bowel obstruction, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
  • 3.67 times higher risk of gastroparesis, limiting the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.

Additionally, the study found a non-significant higher incidence of biliary disease.

The researchers say that although the events are rare, with millions around the world using the drugs, it could still lead to hundreds of thousands of people experiencing these conditions.

“These drugs are becoming increasingly accessible, and it is concerning that, in some cases, people can simply go online and order these kinds of medications when they may not have a full understanding of what could potentially happen. This goes directly against the mantra of informed consent,” said Sodhi.

In the meantime, the researchers hope that regulatory agencies and drug makers will consider updating the warning labels for their products, which currently don’t include the risk of gastroparesis.

“This is critical information for patients to know so they can seek timely medical attention and avoid serious consequences,” said Sodhi.

Source: University of British Columbia