Tag: weight loss

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Could a New Type of Weight‑loss Pill Shake up the Market? Here’s What to Know About Orforglipron

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Photo by Sweet Life on Unsplash

Martin Whyte, University of Surrey

A new type of daily pill has proven more effective for weight loss and blood sugar control than its currently available counterparts, according to a recent trial. The drug, known as orforglipron, could be a game-changer in the rapidly expanding oral weight-loss drug market.

The advent of the injectable weight-loss drug semaglutide (known better by its brand names Wegovy and Ozempic) marked a distinct shift in the weight-loss drugs market when it became available just a few years ago.

Semaglutide is a class of glucagon-like peptide-1 (GLP-1) medication. These drugs mimic the gut hormone GLP-1, which is released soon after eating. This hormone signals fullness to the brain, slowing digestion and stimulating the release of insulin. By replicating the action of this hormone, GLP-1 drugs have proven highly effective at managing type 2 diabetes and promoting weight loss.

Although semaglutide is widely used, a key issue with the drug is that it needs to be injected into the belly, thighs or back of the arm. This can make it difficult for patients with needle phobia or who don’t want to self-inject due to the inconvenience.

Another logistical issue with injectable GLP-1 drugs is that they require refrigeration throughout the supply chain. This can pose a challenge in low- and middle-income countries.

It’s for these reasons that researchers and developers have started investigating the efficacy of oral versions of semaglutide.

Based on current research, it appears that oral semaglutide is very effective. However, it must be taken on an empty stomach – and users must wait 30 minutes before eating or drinking.

Alongside being expensive to produce, it also has poor bioavailability compared with injectable semaglutide. This means only about 1% of the ingested drug is absorbed and able to exert its effects.

But a recent phase 3 clinical trial has shown that a new type of oral weight-loss pill may have overcome these issues – proving to be more effective than the current oral semaglutide products on the market.

Oral weight-loss pill

The recent 52-week phase 3 trial involved 1,698 adults with type 2 diabetes across six countries. It set out to compare current oral semaglutide products against orforglipron, which is also taken as a daily tablet.

The primary measure researchers were looking for was a reduction in HbA1c. This blood test reflecting average blood sugar levels over three months is the standard indicator of diabetes control. Diabetes is present if HbA1c is 6.5% or more.

From a baseline average HbA1c of 8.3%, it was found that after 52 weeks, orforglipron was able to reduce this value by an average of 1.71–1.91%. In comparison, oral semaglutide only reduced HbA1c by 1.47%.

Not only did orforglipron meet the trial’s goals of proving it was as effective to oral semaglutide, it proved it was superior for lowering blood sugar. The participants who took orforglipron also lost more weight – an average of 6.1kg-8.2kg, compared with 5.3kg in those taking semaglutide.

However, a key issue highlighted by the trial was one of tolerability.

GLP-1 drugs can cause gastrointestinal side-effects such as nausea, vomiting, diarrhoea and constipation. In this latest trial, around 59% of participants on orforglipron reported such symptoms, compared with 37–45% on semaglutide.

The reason for this difference may be the more prominent, daily peak drug concentrations with orforglipron. The consequence was that around 10% of orforglipron participants discontinued treatment due to adverse effects. Just 4-5% of those taking semaglutide discontinued treatment.

Future studies may want to look at how orforglipron compares with injectable semaglutide. Photo by Haberdoedas on Unsplash

No head-to-head trials have been done of injectable GLP-1 versus orforglipron. However, the weight loss seen in this study of people with type 2 diabetes is broadly comparable with that previously observed with injectable GLP-1.

Market implications

The trial’s results show that orforglipron, which was developed by Eli Lilly, can be considered one of semaglutide’s most credible challengers.

Another remarkable thing about orforglipron is that it belongs to a new category of drugs called small-molecule drugs. This means it’s a synthetic chemical compound small enough to be absorbed directly through the gut wall. There, it’s able to act on GLP-1 receptors, even though it isn’t of a similar structure to a GLP-1 hormone.

Oral semaglutide, on the other hand, is a peptide drug. This means the structure of its amino acids (one of the building blocks of protein) closely resembles that of the natural GLP-1 hormone.

As a small-molecule drug, orforglipron is cheaper and simpler to manufacture than peptide-based drugs such as semaglutide.

And as with oral semaglutide, it requires no refrigeration. This gives it a logistical advantage over injectable GLP-1 formulations – a potentially important consideration for expanding access in low- and middle-income countries, where cold chain infrastructure is unreliable.

It remains to be seen, however, how orforglipron will perform against oral semaglutide in the broader market.

Although this latest trial has shown it is superior for controlling blood sugar and aiding weight loss, its higher rate of side-effects and treatment discontinuation may temper enthusiasm. In a crowded and competitive market, long-term adherence – shaped as much by tolerability as by efficacy – is probably a critical differentiator.

Orforglipron is still undergoing trials in patients with obesity but without diabetes.

Martin Whyte, Associate Professor of Metabolic Medicine, University of Surrey

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Metabolic DisordersTags :

Specific Brain Signals Rapidly Eliminate Body Fat in Mice

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Photo by Kanashi ZD on Unsplash

Researchers at WashU Medicine have identified a potent pathway that begins in the brain and leads to loss of all body fat without reducing food intake. The study is reported in Nature Metabolism.

The team – led by senior author Erica L. Scheller, DDS, PhD, an associate professor in the Division of Bone and Mineral Diseases in the Department of Medicine; Xiao Zhang, PhD, a former graduate student in Scheller’s lab who is now a postdoctoral fellow at the University of Pennsylvania School of Medicine; and Sree Panicker, a graduate student in Scheller’s lab – was inspired by a unique population of fat cells located deep within the skeleton.

“About 70% of our bone marrow is filled with fat that doesn’t respond to diet or exercise,” said senior author Scheller. “We wanted to figure out why.”

The team found that these special cells, called constitutive bone marrow adipocytes, expressed high levels of proteins that inhibit fat breakdown. This causes resistance to fat loss in day-to-day settings. “We call these cells stable adipocytes,” said Zhang, the study’s first author. In mice, sustained injection of leptin, a hormone, into the brain was able to unlock the stable adipocytes by putting the body into a state of low glucose and insulin. This reduced the inhibitors of fat breakdown, causing complete loss of body fat within days, even though the mice were still eating normally.

This pathway is so powerful that the scientists caution against using it in humans until it is better understood. Stable adipocytes occur in places like the bone marrow, in the hands and feet, and around important glands. In severe wasting disorders, loss of fat within these cells is associated with bone fractures and reduced quality of life. Scheller’s team hopes to prevent this loss and preserve health in patients with severe wasting disorders by defining the mechanisms of stable fat loss. Conversely, methods to activate fat loss from stubborn adipocytes may support future treatments for obesity. This work was funded by the National Institutes of Health (NIH).

By Jaci McDonald

Source: Washington University

Categories : Diet and Nutrition Ethics and LawTags :

Retracted: Widely-reported Trial on Apple Cider Vinegar and Weight Loss

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Journalists and others should no longer reference or use the study findings in future reporting

Photo by Kenny Eliason on Unsplash

BMJ Group has retracted research suggesting that small daily quantities of apple cider vinegar might help people who are overweight or obese to lose weight.

The small clinical trial was published in the open access journal BMJ Nutrition, Prevention & Health in March 2024 and its findings press released. The study findings generated widespread international attention at the time, and continue to be frequently referred to in media coverage.

The retraction was prompted by concerns raised about the quality of the work, including the approach to statistical analysis of the data; implausible statistical values; the reliability of the raw data; inadequate reporting of methods; and lack of prospective trial registration, which breaches BMJ Group’s editorial policy.

Initially, concerns were raised in critiques of the study, some of which were published as letters in the journal. But after review by BMJ Group’s content integrity team, the study was referred to statistical experts to evaluate its reliability.  This included attempts to replicate the results and examine the authenticity of the underlying data supplied by the authors.

It wasn’t possible for the statisticians to replicate the results and multiple analytical errors were identified. There were also irregularities in the data set, and their report, which is appended to the retraction notice, concluded that the data collected from each participant would require further independent scrutiny.

The authors said that the identified errors were honest mistakes, but they agree with the decision to retract the study.

Dr Helen Macdonald, Publication Ethics and Content Integrity Editor at BMJ Group, said: “Tempting though it is to alert readers to an ostensibly simple and apparently helpful weight loss aid, at present the results of the study are unreliable, and journalists and others should no longer reference or use the results of this study in any future reporting.”

She added: “This retraction reflects our strategic and proactive approach to investigating concerns raised about the content we publish. We act where necessary in the interests of openness and the importance of correcting the scientific record.

“While we deal with allegations as swiftly as possible, it’s very important that due process is followed. Investigations are often complex. This one involved detailed scrutiny of data and correspondence with researchers, institutions, and other experts, for example. Reaching a sound and fair and final decision can therefore take several months.”

Commenting on the decision to publish the study despite the lack of trial registration, Professor Martin Kohlmeier, editor in chief of BMJ Nutrition Prevention & Health, explained: “In hindsight, this was the wrong decision to make. But the authors come from a scientific environment that is underrepresented in nutritional research and the journal aims to prioritise high quality evidence, which usually comes from clinical trials.

“These are relatively unusual in nutritional research as they can be challenging to undertake because of the numbers of participants and time needed to obtain meaningful results.”

Source: The BMJ Group

Categories : GastrointestinalTags :

New Expanding Pill for Weight Loss Reduces Hunger Cravings

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An illustration showing how Sirona works. Image credit: Oxford Medical Products

An innovative new pill could soon offer a new and affordable weight management treatment, following a successful clinical trial involving University of Bristol researchers and supported by the National Institute for Health and Care Research (NIHR). The results are published in the journal Obesity.

Sirona by Oxford Medical Products is a hydrogel-based pill that is designed to aid weight loss by reducing hunger.  After it is swallowed, the pill expands in the stomach, leading to faster satiety. This helps individuals to eat less without needing strong medications or injections.

Thirty-nine participants in Southampton took part at the NIHR Southampton Clinical Research Facility.

In the trial, funded by Innovate UK, participants lost up to 13.5% of their body weight in just six months. On average, people with class 1 obesity (BMI 30-35) lost 6.4% of their body weight.

Participants also ate on average 400 fewer calories per day compared to those taking a placebo. For context, recent Government-led research suggests that even a 216-calorie daily reduction could cut the UK’s obesity rate in half.

The trial was led by chief investigator Professor James Byrne in the NIHR Southampton Biomedical Research Centre.

Mr Byrne, a consultant surgeon at University Hospital Southampton, said: “Obesity is a chronic and often progressive disease. With obesity rates continuing to rise, these results are an important step towards providing a different treatment option.

“This trial demonstrated Sirona could be a safe, affordable, and non-pharmacological treatment to support long-term weight management.”

Sirona will be accessible to anyone with a BMI 25-40, which means Sirona is particularly well-suited to help two key patient types. Firstly, for patients with an overweight BMI (25–30), allowing them to proactively manage their weight and to avoid progressing into obesity and the serious health problems it can bring. Secondly, it is suitable for use as an ‘off-ramp’ for GLP-1 users looking to come off treatment but prevent weight regain, which often occurs once GLP-1 medication ceases.

GLP-1 medications have become very popular for weight loss, with around 1.5 million users in the UK. However, a significant proportion of users pay out of pocket and prices have recently doubled in the UK for some doses of Mounjaro.

Camilla Easter, CEO of Oxford Medical Products, added: “GLP-1 medications perform an important role in helping those with a BMI in the obese range to lose weight and reduce weight-related health risks. There is, however, a real opportunity for a new style of treatment to work in a complementary way to GLP-1s, in a format that is significantly less expensive, and with better tolerability and therefore more accessible for the majority.

“Sirona has demonstrated amazing results during testing with UK hospitals, which have now been externally peer-reviewed. Next, we are setting sights on commercial UK release plans, targeting 2027 to make Sirona available.”

Sirona is a dual-polymer hydrogel pill. That means it’s made from two types of safe materials that expand in the stomach. It doesn’t use drugs or chemicals to change how your body works.

The pill was well tolerated during the 24-week study. There were no serious adverse events. Participants lost up to 13.5% of their body weight in just 24 weeks, and individuals with class 1 obesity (BMI 30-35) lost 6.4% of their body weight on average.

Importantly, no serious adverse events were reported during the trial. Sirona was well tolerated (95 percent of patients adhered to the dosing regimen at 12 weeks) and demonstrated a fantastic safety and side effect profile. This makes Sirona appropriate for patients who have struggled with adverse side effects when using GLP-1 medications. 

OMP is planning a pivotal study in the UK and USA to further assess the effectiveness of Sirona and confirm these results. The novel weight loss treatment will aim for a 2027 UK commercial launch.

Source: University of Bristol

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Prediabetes Remission Possible Without Dropping Pounds, Our New Study Finds

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Photo by Kenny Eliason on Unsplash

Andreas L. Birkenfeld, University of Tübingen and Reiner Jumpertz-von Schwartzenberg, University of Tübingen

There’s a long-held belief in diabetes prevention that weight loss is the main way to lower disease risk. Our new study challenges this.

For decades, people diagnosed with prediabetes – a condition affecting up to one in three adults depending on age – have been told the same thing by their doctors: eat healthily and lose weight to avoid developing diabetes.

This approach hasn’t been working for all. Despite unchanged medical recommendations for more than 20 years, diabetes prevalence continues rising globally. Most people with prediabetes find weight-loss goals hard to reach, leaving them discouraged and still at high risk of diabetes.

Our latest research, published in Nature Medicine, reveals a different approach entirely. We found that prediabetes can go into remission – with blood sugar returning to normal – even without weight loss.

About one in four people in lifestyle intervention programmes bring their blood sugar back to normal without losing any weight. Remarkably, this weight-stable remission protects against future diabetes just as effectively as remission achieved through weight loss.

This represents a significant shift in how doctors might treat overweight or obese patients at high risk for diabetes. But how is it possible to reduce blood glucose levels without losing weight, or even while gaining weight?

The answer lies in how fat is distributed throughout the body. Not all body fat behaves the same way.

The visceral fat deep in our abdomen, surrounding our internal organs, acts as a metabolic troublemaker. This belly fat drives chronic inflammation that interferes with insulin – the hormone responsible for controlling blood sugar levels. When insulin can’t function properly, blood glucose rises.

In contrast, subcutaneous fat – the fat directly under our skin – can be beneficial. This type of fat tissue produces hormones that help insulin work more effectively. Our study shows that people who reverse prediabetes without weight loss shift fat from deep within their abdomen to beneath their skin, even if their total weight stays the same.

Subcutaneous fat can be beneficial. Photo by Andres Ayrton on Pexels

We’ve also uncovered another piece of the puzzle. Natural hormones that are mimicked by new weight-loss medications like Wegovy and Mounjaro appear to play a crucial role in this process. These hormones, particularly GLP-1, help pancreatic beta cells secrete insulin when blood sugar levels rise.

People who reverse their prediabetes without losing weight seem to naturally enhance this hormone system, while simultaneously suppressing other hormones that typically drive glucose levels higher.

Targeting fat redistribution, not just weight loss

The practical implications are encouraging. Instead of focusing only on the scales, people with prediabetes can aim to shift body fat with diet and exercise.

Research shows that polyunsaturated fatty acids, abundant in Mediterranean diets rich in fish oil, olives and nuts, may help reduce visceral belly fat. Similarly, endurance training can decrease abdominal fat even without overall weight loss.

This doesn’t mean weight loss should be abandoned as a goal – it remains beneficial for overall health and diabetes prevention. However, our findings suggest that achieving normal blood glucose levels, regardless of weight changes, should become a primary target for prediabetes treatment.

This approach could help millions of people who have struggled with traditional weight-loss programmes but might still achieve meaningful health improvements through metabolic changes.

For healthcare providers, this research suggests a need to broaden treatment approaches beyond weight-focused interventions. Monitoring blood glucose improvements and encouraging fat redistribution through targeted nutrition and exercise could provide alternative pathways to diabetes prevention for patients who find weight loss particularly difficult.

The implications extend globally, where diabetes represents one of the fastest-growing health problems. By recognising that prediabetes can improve without weight loss, we open new possibilities for preventing a disease that affects hundreds of millions worldwide and continues rapidly expanding.

This research fundamentally reframes diabetes prevention, suggesting that metabolic health improvements – not just weight reduction – should be central to clinical practice. For the many people living with prediabetes who have felt discouraged by unsuccessful weight-loss attempts, this offers renewed hope and practical alternative strategies for reducing their diabetes risk.

Andreas L. Birkenfeld, Professor, Diabetology, Endocrinology and Nephrology, University of Tübingen and Reiner Jumpertz-von Schwartzenberg, Professorship for Clinical Metabolism and Obesity Research, University Hospital and Medical Faculty, University of Tübingen

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Metabolic DisordersTags :

Focusing on Weight Loss Alone for Obesity May Do More Harm than Good

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A healthy lifestyle has important benefits, but weight alone might not give an adequate picture of someone’s health, say experts

Source: Pixabay CC0

Focusing solely on achieving weight loss for people with a high body mass index (BMI) may do more harm than good, argue experts in The BMJ.

Dr Juan Franco and colleagues say, on average, people with high weight will not be able to sustain a clinically relevant weight loss with lifestyle interventions, while the potential harms of weight loss interventions, including the reinforcement of weight stigma, are still unclear.

They stress that a healthy lifestyle has important benefits, but that weight alone might not give an adequate picture of someone’s health, and say doctors should provide high quality, evidence based care reflecting individual preferences and needs, regardless of weight.

Lifestyle interventions that focus on restricting an individual’s energy intake and increasing their physical activity levels have for many decades been the mainstay recommendation to reduce weight in people with obesity, explain the authors.

However, rigorous evidence has indicated that these lifestyle interventions are largely ineffective in providing sustained long term weight loss and reducing cardiovascular events (eg, heart attacks and strokes) or death.

Even though a healthy lifestyle provides important benefits, acknowledging that weight alone might not give an adequate picture of someone’s health, and recognising the limitations of lifestyle interventions for weight loss, could pave the way for more effective and patient centred care, they say.

Focusing on weight loss might also contribute to societal weight bias – negative attitudes, assumptions, and judgments about people based on their weight – which may not only have adverse effects on mental health but may also be associated with disordered eating, the adoption of unhealthy habits, and weight gain, they add.

They point out that recent clinical guidelines reflect the growing recognition that weight is an inadequate measure of health, and alternative approaches, such as Health at Every Size (HAES), acknowledge that good health can be achieved regardless of weight loss and have shown promising results in improving eating behaviours.

While these approaches should be evaluated in large clinical trials, doctors can learn from them to provide better and more compassionate care for patients with larger bodies, they suggest.

“Doctors should be prepared to inform individuals seeking weight loss about the potential benefits and harms of interventions and minimise the risk of developing eating disorders and long term impacts on metabolism,” they write. “Such a patient centred approach is likely to provide better care by aligning with patient preferences and circumstances while also reducing weight bias.”

They conclude: “Doctors’ advice about healthy eating and physical activity is still relevant as it may result in better health. The main goal is to offer good care irrespective of weight, which means not caring less but rather discussing benefits, harms, and what is important to the patient.”

Source: BMJ Group

Categories : Metabolic DisordersTags :

Study Reveals the Hidden Benefits of Weight Loss on Fat Tissue

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Photo by Andres Ayrton on Pexels

Scientists have produced the first detailed characterisation of the changes that weight loss causes in human fat tissue by analysing hundreds of thousands of cells. They found a range of positive effects, including clearing out of damaged, ageing cells and increased metabolism of harmful fats.

The researchers say the findings help to better understand how weight loss leads to health improvements at a molecular level. In  the future this could help to inform the development of therapies for diseases such as type 2 diabetes.

The study

The study, published in Nature, compared samples of fat tissue from healthy weight individuals with samples from people with severe obesity, meaning a BMI over 35, undergoing bariatric weight loss surgery.

The weight loss group had fat samples taken during surgery and more than five months after surgery, at which point they had lost an average of 25kg.

Lipid recycling

The researchers, who were from the Medical Research Council (MRC) Laboratory of Medical Sciences and Imperial College London, analysed gene expression in more than 170,000 cells that made up the fat tissue samples, from 70 people.

They unexpectedly found that weight loss triggers the breakdown and recycling of fats called lipids.

This recycling process could be responsible for burning energy and reversing the harmful build-up of lipids in other organs like the liver and pancreas.

The researchers say that further study will be needed to establish if lipid recycling is linked to the positive effects of weight loss on health, such as remission of type 2 diabetes.

Senescent cells

They also found that the weight loss cleared out senescent cells, which are ageing and damaged cells that accumulate in all tissues.

The senescent cells cause harm because they no longer function properly and release signals that lead to tissue inflammation and scarring.

Immune system

In contrast, the researchers found that weight loss did not improve the effects of obesity on certain aspects of the immune system.

They found that inflammatory immune cells, which infiltrated the fat of people with obesity, did not fully recover even after weight loss.

This type of inflammatory cell memory could be harmful in the long term if people regain weight.

Detailed map of what drives health benefits

Dr William Scott, from the MRC Laboratory of Medical Sciences and from Imperial College London, who led the study, said:

We’ve known for a long time that weight loss is one of the best ways to treat the complications of obesity, such as diabetes, but we haven’t fully understood why. This study provides a detailed map of what may actually be driving some of these health benefits at a tissue and cellular level.

Fat tissues have many underappreciated health impacts, including on blood sugar levels, body temperature, hormones that control appetite, and even reproductive health.

We hope that new information from studies like ours will start to pave the way for developing better treatments for diabetes and other health problems caused by excess body fat.

Source: UK Research and Innovation

Categories : Metabolic Disorders New Compounds and TreatmentsTags :

New Weight Loss Drug Targets Four Hormone Receptors

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Photo by I Yunmai on Unsplash

In the US, drugs like semaglutide are used by over 15 million adults in the U.S., or 4.5% of the population for diabetes and also weight loss. Despite their effectiveness, they have drawbacks. Their effect may not last after discontinuing use, and side effects including osteoporosis and muscle loss have raised concerns about long-term harms. They also induce nausea, which can make it difficult to stay the course of treatment.

Now Tufts researchers led by Professor Krishna Kumar, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society. 

While weight loss drugs currently on the market and in development target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could potentially further enhance the control strategy.

“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”

How the Drugs Work

After a meal, the hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Semaglutide uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.

But GLP-1 also acts directly on the brain, prompting satiety after a meal, and it slows down the rate at which stomach contents are emptied into the intestines, evening out the release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.

It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”

A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both – what’s called in drug development a chimera. That drug, tirzepatide, has the added benefit of significantly reducing nausea. As a more tolerable treatment, it may overtake semaglutide in the weight loss market. 

“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raises body temperature, and suppresses appetite.” By adding glucagon to the mix, GLP-1 and GIP end up neutralizing its glucose-enhancing effect, leaving the remaining functionalities of all three hormones working together to enhance weight loss.

Glucagon is also similar in structure to GLP-1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognised by their three separate receptors. That drug, called retatrudide, is currently in clinical trials that indicate even greater achievable weight loss (up to 24%) compared to the original GLP-1 drugs (6-15%).

Going for the Weight Loss Gold Standard with a Fourth Target

“The goal that people are trying to shoot for is bariatric surgery,” said Kumar. That’s a surgical procedure significantly reducing the size of the stomach, which can achieve long-lasting weight loss up to 30%. “For individuals with persistent obesity and potential deadly associated conditions, it becomes a necessary but invasive treatment.” 

Current injectable weight loss drugs still fall short of that gold standard, so the Tufts chemists are focused on a drug redesign that could match the 30% weight loss outcome. 

“There is one more hormone we wanted to bring in to complete a weight control quartet,” said Tristan Dinsmore, a graduate student in the Kumar lab and the lead author of the study. “It’s called peptide YY (PYY). This molecule is also secreted by the gut after we eat a meal, and its job is to reduce appetite and slow the process of emptying food from the stomach, but via different mechanisms than either GLP-1 or GIP. It may also be involved in directly ‘burning off’ fat.”

PYY is from a separate and structurally unrelated class of hormones than the first three, so blending its structure into a chimeric peptide that also mimics GLP-1, GIP, and glucagon was not easy. Instead, the Tufts team was able to join two peptide segments end-to-end, creating a new ‘tetra-functional’ clinical candidate.

“One of the limitations of the current drugs is that individual variation, possibly including how people express target receptors or respond to their corresponding hormones, can lead to lesser than desired weight loss outcomes in many patients,” said Martin Beinborn, visiting scholar in the Department of Chemistry. “By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness.”

“A second issue is that patients tend to regain weight after discontinuing currently available GLP-1 related drugs,” said Beinborn, who notes that lifestyle changes should ideally be a complement to medication treatment. This two-pronged approach will not only support reaching and keeping one’s target weight, but may also help preserve bone and muscle mass.

“Recent studies indicate that weight rebound after drug discontinuation is delayed with the newer, more effective GLP-1 mimetics,” he said. “Extending from this observation, one may speculate that multi-chimeras along the lines of the one we discovered could get us closer to the bariatric surgery standard of lasting weight loss.”

Source: Tufts University

Categories : Ageing Metabolic DisordersTags :

Midlife Weight Loss Linked to Longer, Healthier Lives

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Photo by I Yunmai on Unsplash

Losing weight via lifestyle adjustments can deliver significant long-term health benefits, without the need for surgery or anti-obesity drugs. Alongside preventing diabetes, it can help ward off chronic conditions including arterial and pulmonary diseases as well as cancers.

A University of Helsinki study tracked 23 000 individuals from Finland and the UK, aged 30 to 50 at the outset, over a period of 12 to 35 years. Health benefits were found in overweight men and women who lost an average of 6.5% of their body weight in early middle age and maintained it throughout the 12–35-year follow-up period. Weight maintenance is crucial. 

“The benefits of lifestyle-based weight management are widely discussed even though studies have found it surprisingly difficult to demonstrate health benefits beyond the prevention of diabetes,” notes Professor Timo Strandberg.  

The study he led is now filling this gap. 

“I hope the findings will inspire people to see that lifestyle changes can lead to major health improvements and a longer life. This is particularly important today as more people are overweight than when the collection of our research data began 35 years ago.” 

The study also supports the view that, for optimal health, a lifelong body mass index (BMI) under 25 is ideal.   

The study was published in JAMA Network Open, the open-access journal of the American Medical Association.

Source: University of Helsinki

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.