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New study finds financial rewards enhance obesity interventions for teens
A recent study has demonstrated that adolescents suffering from severe obesity achieve a more significant reduction in body mass index (BMI) when meal-replacement therapy is supplemented with financial incentives, as opposed to meal-replacement therapy alone. These findings have been documented in an article published by JAMA Pediatrics.
Justin Ryder, PhD, an associate professor involved in both the Surgery Division of Pediatric Surgery and Pediatrics, collaborated on this research. Ryder highlighted the importance of developing more effective treatments for severe obesity, which currently impacts approximately 20% of children and adolescents in the U.S. The Centers for Disease Control and Prevention defines severe obesity as having a BMI at or above the 95th percentile for one’s age and gender. This condition predisposes individuals to a host of future health issues including adult obesity, cardiovascular diseases, and type two diabetes.
Previous studies have shown that meal replacement therapy (MRT), which replaces regular meals with controlled, pre-portioned meals totalling 1,200 calories per day, tends to be more effective than traditional lifestyle changes for reducing BMI in young people with severe obesity. In light of these findings, the recent study aimed to assess whether the addition of financial incentives would enhance the effectiveness of MRT.
“There’s literature for adults that supports that tying in financial incentives to weight loss or physical activity programs increases adherence, and so we wanted to see whether or not adding financial incentives to a behavioural/nutrition weight loss program using meal replacement therapy would increase adherence and through adherence, increase the efficacy of the treatment,” explained Ryder.
The research involved 126 adolescents, divided into two groups of 63 participants each. For one year, one group received MRT along with financial incentives based on their weight reduction from baseline, while the other group received only the MRT. At the end of the 52-week period, the group that received both MRT and financial incentives exhibited a greater decrease in BMI—by 6 percentage points—and a higher reduction in total body fat mass—4.8 kilograms compared to their counterparts who only received MRT.
Ryder added, “Using a cost-effectiveness analysis, we looked at mean fat mass lost between the two treatments and found that despite providing the additional meal replacements for per pound lost, it was cost-effective to do so.”
The study’s authors also noted the need for the development of interventions that maintain effectiveness beyond a one-year timeframe. “While financial incentives plus MRT appears to be a longer-term strategy than MRT alone, treatment withdrawal will likely result in BMI increase. As such, research is needed to identify strategies that are scalable and feasible in the long term given the chronic nature of obesity,” they mentioned.
This pivotal research was funded by multiple grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health National Center for Advancing Translational Sciences. Financial support for the meal programs was provided by Healthy For Life Meals, contributing to the resources necessary for this comprehensive study.
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Significant weight loss improves metabolism, mood, and decision-making in individuals with obesity
Severe obesity not only predisposes individuals to a variety of health risks but also significantly alters their metabolic functions and psychological states. Historically, it was believed that individuals with severe obesity tended to display heightened impulsivity and a greater propensity for risk-taking. However, recent research conducted by scientists at the DZD partner German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) has explored whether substantial weight loss could reverse these effects, enhancing both metabolic and psychological conditions and thereby improving decision-making processes. These findings have been elucidated in the publication ‘Clinical Nutrition‘.
Human behaviour is influenced by a myriad of factors including personality traits and internal physiological signals like glucose metabolism and mood states. In individuals with obesity, these internal signals are often disrupted, leading to unreliable decision-making foundations. Beatrix Keweloh, a doctoral researcher in the Department of Neuroscience of Decision and Nutrition, spearheaded an intervention study to investigate if these impairments could be reversed through significant weight loss. The study involved 62 participants, aged 18 to 75, all with severe obesity (BMI > 35 kg/m2). They underwent a rigorous 10-week diet limiting their daily caloric intake to 800 kilocalories.
Measurements of participants’ weight, body fat, mood (via a questionnaire), and risk-taking tendencies (using a computer-based test) were taken at both the start and conclusion of the diet. Results demonstrated a considerable decrease in BMI and HbA1c levels—markers of glucose metabolism—and notable improvements in mood. Additionally, there was a shift towards more risk-averse behaviours, suggesting a direct correlation between BMI and risk behaviour in individuals with obesity. “Our findings also indicated that the metabolic factor HbA1c becomes a predominant predictor of risk-taking behaviours post-weight loss,” commented Beatrix Keweloh.
The study further noted that post-weight loss, mood had a diminished impact on decision-making, with metabolic signals becoming the primary influencers of risk behaviour. “Weight loss positively impacts glucose metabolism and mood, and importantly, restores the regulatory function of glucose metabolism in decision-making processes,” Keweloh summarised.
The interplay between weight loss and the metabolic and psychological factors influencing risk-taking is intricate, with BMI playing a pivotal role. A reduced propensity for risk-taking correlates with a healthier lifestyle, crucial for both achieving and maintaining a healthy body weight. Consequently, interventions aimed at managing weight should incorporate both metabolic and psychological considerations to prevent relapses and foster metabolically driven decisions.
“This study is pioneering as it considers both metabolic and psychological aspects in overweight individuals,” stated Prof. Soyoung Q Park, head of the Department of Neuroscience of Decision and Nutrition. “It marks a significant contribution to the field, although it also highlights the necessity for further research to fully comprehend how energy balance and psychological factors influence our choices.”
Globally, the prevalence of obesity is escalating rapidly. According to a report in the British journal ‘Lancet’, over one billion individuals are affected worldwide, out of a global population of approximately eight billion. Data from the Federal Statistical Office reveal that in Germany alone, around 42 percent of women and 62 percent of men are considered to have either overweight or obesity. The World Health Organization (WHO) classifies individuals with a BMI over 25 as having overweight and over 30 as having obesity.
In studies assessing risk-taking tendencies, various methodologies are employed, such as computerised lottery tasks. In this particular study, a conventional lottery task was utilised where participants made choices between a guaranteed monetary amount and a variable amount, with a 50 percent chance of winning in each scenario.
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Natural compound found in olives shown to lower blood sugar and aid weight loss, mouse study shows
A novel study conducted using mice models has highlighted the potential of elenolic acid, a natural compound extracted from olives, in mitigating obesity and type 2 diabetes. This groundbreaking research suggests that elenolic acid could serve as a basis for the development of affordable, safe natural products aimed at managing these prevalent health issues.
In a series of experiments, diabetic mice with obesity administered with elenolic acid orally displayed a significant reduction in body weight and enhanced glucose regulation within just one week. These results were noteworthy when compared to a control group of mice with obesity that did not receive the treatment. Remarkably, the glucose-lowering impact of elenolic acid was on par with liraglutide, an injectable diabetes medication, and surpassed the effectiveness of metformin, a commonly used oral diabetes drug.
Professor Dongmin Liu, the lead researcher and a professor at the Department of Human Nutrition, Foods and Exercise at Virginia Tech, explained the motivation behind their focus on natural compounds. “Lifestyle modifications and public health measures have had limited impact on the rising prevalence of obesity, one of the top risk factors for type 2 diabetes. Available obesity drugs are ineffective in weight loss maintenance, expensive and/or carry potential long-term safety risks. Our goal was to develop safer, cheaper and more convenient multi-targeting agents that can prevent the occurrence of metabolic disorders and type 2 diabetes,” stated Liu.
The research findings will be presented by Dr. Hana Alkhalidy, a scientist in Liu’s laboratory, at NUTRITION 2024, the premier annual event of the American Society for Nutrition.
The team at Virginia Tech has previously investigated various natural compounds targeting molecular aspects of metabolism in critical body parts like the pancreas, muscle, fat tissues, and liver. Their latest strategy focuses on stimulating hormone secretion in the gut, a method that could indirectly improve metabolic functions due to natural products’ generally poor bioavailability.
Their screening identified that elenolic acid, found abundantly in mature olives and extra virgin olive oil, stimulates the release of metabolic hormones GLP-1 and PYY in the gut. These hormones are integral during meals, enhancing satiety and regulating blood sugar and metabolism. The researchers synthesized elenolic acid from its precursor, oleuropein, which proved to be a cost-effective method compared to direct extraction from olives.
Further testing revealed that diabetic mice with obesity treated with elenolic acid for four to five weeks showed a 10.7% reduction in obesity and exhibited glucose levels and insulin sensitivity comparable to healthy, lean mice. Additionally, the treatment significantly curbed food intake and fostered weight loss, effects associated with increased levels of PYY and GLP-1 and decreased expression of agouti-related peptide, a hypothalamic peptide that promotes overeating and weight gain when overexpressed.
“Overall, the study showed that elenolic acid from olives has promising effects on hormone release and metabolic health, particularly in obese and diabetic conditions,” Liu remarked. He noted that the compound mimics the physiological conditions of eating to enhance gut metabolic hormone secretion, thereby helping to regulate energy balance and metabolic health.
Despite these promising results, the researchers cautioned that the concentration of elenolic acid in typical olive products is quite low, implying that the health benefits observed in the study are unlikely to be replicated through consumption of olives and olive oil alone.
The research team is now focused on elucidating the metabolic pathway of elenolic acid, from its absorption to its excretion. This exploration will provide further insights into the compound’s efficacy and safety, paving the way for potential clinical trials.
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Innovative obesity drug pemvidutide maintains muscle mass in Altimmune trials
Altimmune, a biotechnology company, recently shared encouraging results from their Phase II MOMENTUM study concerning their investigational obesity treatment, pemvidutide. The study data, which was presented at the 84th Scientific Sessions of the American Diabetes Association, revealed that pemvidutide not only facilitates significant weight loss in adults diagnosed with obesity but also uniquely preserves lean muscle mass.
Participants in the study who were administered a 1.2-mg dose of pemvidutide experienced an average weight reduction of 10.3% over a period of 48 weeks. This average increased to 11.2% for those on the 1.8-mg dosage and reached 15.6% for subjects receiving the 2.4-mg dose. In stark contrast, the placebo group saw a minimal weight loss of just 2.2% under the same conditions.
A detailed assessment involving full-body MRI scans of fifty individuals treated with pemvidutide showcased the drug’s capability to significantly maintain lean body mass. The body composition analysis indicated that 78.1% of the weight loss was due to fat reduction, whereas the loss of lean muscle mass constituted only 21.9%.
Additionally, improvements were noted in serum lipid levels and blood pressure among the pemvidutide recipients, with no clinically significant increases in heart rate or any notable imbalances in arrhythmias and other cardiac events being observed.
Vipin Garg, CEO of Altimmune, expressed satisfaction with the results, stating, “We are pleased with the data from MOMENTUM, which highlight the impressive lean mass preservation achieved with pemvidutide.” He further commented on the significance of maintaining muscle mass, which he deemed essential for healthy weight loss and optimal physical function. Garg also remarked that the outcomes with pemvidutide surpass those typically observed with conventional diet and exercise regimes, as well as other incretin-based weight loss treatments which reportedly lose about 40% of weight as lean mass.
Garg believes that the notable muscle preservation seen in the MOMENTUM study could distinctly position pemvidutide in the obesity treatment landscape.
Pemvidutide functions as a peptide-based agonist targeting both GLP-1 and glucagon receptors, which play roles in suppressing appetite and boosting energy expenditure, respectively. The dual mechanism of pemvidutide not only promotes weight loss but also mimics the physiological effects of exercise and diet on the body.
Looking forward, Altimmune has planned an end-of-Phase II meeting with the FDA, set for the third quarter of 2024. Approval of pemvidutide could position it as a significant treatment option for adults struggling with obesity. Moreover, the company is investigating pemvidutide’s potential in treating metabolic dysfunction-associated steatohepatitis in the ongoing Phase II IMPACT study, with a topline readout expected in the first quarter of 2025.
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India and China to introduce cheaper alternatives to popular obesity medications
As global demand for effective weight-loss medications surges, pharmaceutical companies in India and China are poised to disrupt the market by introducing cheaper versions of established obesity drugs, such as Wegovy. These firms are in the process of developing biosimilars, which are highly similar to original biologic drugs but are typically more affordable. This development is expected to make these crucial treatments accessible to a broader audience, especially in regions burdened with high rates of obesity.
Abhijit Zutshi, the Chief Commercial Officer at Biocon, headquartered in Bengaluru, India, highlighted the significant potential for Indian and Chinese companies to enhance global access to these medications. “There is huge potential for companies from India, China that can help create access to these drugs,” Zutshi explained, underlining the goal of providing affordable healthcare solutions to those in need.
The urgency is underscored by the alarming prevalence of obesity and overweight conditions globally, affecting approximately one billion individuals, many of whom reside in India and China. “Demand for anti-obesity drugs is very strong,” affirmed Lei Qian, Vice-President of Clinical Development at Innovent Biologics in Shanghai, illustrating the critical need for effective and accessible treatment options in these populous nations.
The drive to develop biosimilars is fueled by the success of a new class of weight-loss drugs that mimic the glucagon-like peptide 1 (GLP-1), a hormone that plays a crucial role in regulating blood sugar and appetite. The U.S. Food and Drug Administration (FDA) first approved GLP-1 drugs for weight loss in 2014, starting with Liraglutide (Saxenda). Subsequent developments led to more advanced formulations such as semaglutide (Wegovy) and tirzepatide (Zepbound), which offer significant weight loss benefits through weekly injections.
Despite their effectiveness, the cost of these treatments remains a barrier for many, with monthly expenses exceeding US$1,000. In response, companies like Biocon are innovating in drug synthesis and delivery to reduce these costs significantly. Zutshi remains optimistic about the potential for price reductions, suggesting that “it could be cut in half, or be one-tenth the current price.”
The patent landscape in China and India is rapidly evolving, with the patent for liraglutide already expired in China and semaglutide’s patent set to expire in 2026 in both countries. This change will allow more companies to produce and sell biosimilar versions, intensifying competition and potentially leading to further price reductions.
In addition to biosimilars, there are efforts underway to innovate beyond the existing drug formulas. For instance, Sun Pharmaceuticals in Mumbai is developing a new molecule, GL0034, which shows promise in early-stage trials to reduce body weight by up to 10% in just two months. Furthermore, a partnership between Innovent and Eli Lilly is focusing on Mazdutide, a dual-target drug that mimics both GLP-1 and glucagon, enhancing metabolism and fat burning. Lei anticipates that Mazdutide could receive approval from China’s drug regulator by the first half of 2025, marking a significant advancement in the treatment of obesity.
The introduction of these biosimilars and new drug formulations represents a transformative shift in the treatment of obesity, with the potential to make these life-changing medications accessible to millions more around the globe. As these developments unfold, the landscape of obesity treatment is set to change significantly, offering new hope and expanded options for those seeking to manage their weight effectively.
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Nuts can aid in weight loss efforts, research shows
Nuts, often enjoyed as a topping on morning cereal or as a mid-afternoon nibble, may play a pivotal role in effective weight management strategies, according to new research findings.
A study conducted by the University of South Australia has found that nuts can be a beneficial component of calorie-restricted diets aimed at weight loss. The research, which synthesised data from seven randomised controlled trials, assessed the impact of nut inclusion on weight loss and glycemic control within energy-restricted (ER) diets. The findings indicated that including nuts did not negatively affect weight loss outcomes; on the contrary, it may enhance them.
The analysis revealed that in four out of the seven studies, participants who incorporated between 42 to 84 grams of nuts daily into their ER diets experienced significantly greater weight loss—ranging from an additional 1.4 to 7.4 kilograms—compared to those on similar diets without nuts. This weight loss benefit is thought to stem from nuts’ ability to effectively suppress appetite.
In instances where no discernible difference in weight loss was observed between nut-enriched and nut-free diets, the quantity of nuts included in the diets was generally lower.
This research arrives amidst concerning statistics from the Australian Bureau of Statistics, which indicate that 67% of Australian adults are either overweight or obese. Thus, the study’s insights are particularly timely and relevant.
Professor Alison Coates from UniSA highlighted the nutritional value of nuts, advocating for their inclusion in weight-loss diets. “Many people shun nuts in their diet due to the misconception that their high energy and fat content contribute to weight gain,” Professor Coates explained. However, she clarified that nuts are abundant in healthy unsaturated fats, plant proteins, and dietary fibre, all of which aid in promoting fullness and reducing overeating. She also noted nuts’ association with improved cardiovascular health, better gut health, and enhanced cognitive function.
Despite these benefits, it appears that nut consumption among Australians is less than ideal, with 60% of the population reporting they do not consume any nuts at all.
Professor Coates reassured that, contrary to common fears, nuts do not promote weight gain. “If concerns about weight gain have been deterring people from consuming nuts, they need not worry. Nuts do not lead to weight gain and seem to actually support weight loss efforts,” she asserted.
Dr Sharayah Carter, a co-author of the study, also celebrated the findings. She emphasised the unique flavour and texture profile of nuts, which make them an integral part of many diets, and highlighted their convenience as a healthy snack option. “For those who enjoy nuts, it is heartening to know that they can contribute to achieving weight-loss objectives while also enhancing overall health,” Dr Carter said. She added that health professionals should feel confident in recommending nuts as part of a healthy diet, with no adverse effects on weight management.
This study underscores the role of nuts as a beneficial addition to weight loss diets, helping to debunk myths about their dietary impact while promoting their numerous health advantages.
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Bariatric surgery tops GLP-1 drugs and lifestyle changes in sustained weight loss efficacy
An extensive review of medical research from 2020 to 2024 has conclusively demonstrated that bariatric surgery, also referred to as metabolic or weight-loss surgery, yields the most substantial and longest-lasting weight loss results when compared to other interventions such as GLP-1 receptor agonists and lifestyle modifications. This significant finding was unveiled at the American Society for Metabolic and Bariatric Surgery (ASMBS) 2024 Annual Scientific Meeting.
According to the research, lifestyle modifications, encompassing diet and physical exercise, typically lead to an average weight reduction of 7.4%. However, the study notes that this weight is often regained within approximately 4.1 years. In contrast, more intensive interventions like GLP-1 receptor agonists and surgical procedures have shown greater efficacy. The studies analysed involved thousands of participants across various clinical and randomised trials.
The research highlighted the effectiveness of GLP-1 semaglutide, which, with five months of weekly injections, resulted in a 10.6% reduction in body weight. A more pronounced effect was observed with tirzepatide, where nine months of treatment led to a 21.1% weight loss. Nevertheless, approximately half of this weight was regained within a year after cessation of treatment with either drug. If treatment was sustained, patients receiving tirzepatide stabilised at a 22.5% weight loss after 17-18 months, while those on semaglutide reached a plateau at 14.9% during the same timeframe.
More profound outcomes were observed with metabolic and bariatric surgeries such as gastric bypass and sleeve gastrectomy. These procedures showed a total weight loss of 31.9% and 29.5% respectively, one year post-operation. Remarkably, a weight loss of around 25% was maintained for up to a decade following the surgery.
“Metabolic and bariatric surgery remains the most effective and durable treatment for severe obesity,” explained Marina Kurian MD, a co-author of the study and bariatric surgeon at NYU Langone Health. She further emphasised the underutilisation of such surgeries, advocating for their consideration earlier in the treatment process rather than as a last resort.
In 2022, approximately 280,000 metabolic and bariatric procedures were conducted in the U.S., representing just about 1% of the eligible population based on Body Mass Index (BMI) criteria. This is in the context of a prevailing obesity rate of 42.4% among Americans, as reported by the U.S. Centers for Disease Control and Prevention (CDC). Obesity is known to compromise the immune system, enhance chronic inflammation, and escalate the risk of numerous health issues including cardiovascular diseases, stroke, type 2 diabetes, and certain types of cancer.
Dr. Ann Rogers, ASMBS President-elect and Professor of Surgery at Penn State College of Medicine, who was not involved in the study, highlighted the importance of surgical interventions in combating obesity. “While new drug treatments show great promise and could lead to more successful outcomes, particularly with better affordability and insurance coverage, we are still not fully utilising the most effective tool we have—metabolic and bariatric surgery, which is safer and more effective than ever,” she stated.
The study comprised a systematic review of various research studies that explored weight loss through lifestyle changes, GLP-1s (Semaglutide or tirzepatide), or metabolic and bariatric surgery. The review of GLP-1s was based on four randomised clinical trials conducted between 2021 and 2024. Lifestyle interventions were examined across eight studies, while surgical approaches were evaluated through a review of 35 studies, including two randomised trials, covering approximately 20,000 patients in total.
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Integrating obesity experts into primary care clinics enhances patient weight loss outcomes
A novel study conducted by the University of Michigan reveals significant benefits in integrating obesity specialists into primary care settings, resulting in substantial weight loss for high-risk patients. This approach, piloted by Michigan Medicine’s academic medical centre through the Weight Navigation Program (WNP), has been proven to facilitate access to evidence-based weight management treatments and support patients in achieving notable weight reduction within a year.
Primary care practitioners often find it challenging to devise personalised weight management plans during brief consultations. Earlier investigations by the University have indicated that a majority of primary care patients with obesity fail to lose at least 5% of their body weight—an outcome that substantially decreases obesity-related health risks.
To address this, the Weight Navigation Program was established in the autumn of 2020, pairing obesity specialists with patients and their primary care providers to collaboratively develop tailored obesity treatment plans. The effectiveness of this initiative was evaluated in a study recently published in JAMA Network Open, carried out by a multidisciplinary team responsible for initiating the WNP.
Results from the first year of the programme indicated an average weight loss of about 12 pounds (approximately 4.4% of body weight) among participants, compared to minimal weight loss in a similar group from another clinic without access to the WNP. Participants typically started with a body mass index (BMI) around 40 kg/m^2, with eligibility for the WNP requiring a BMI over 30 kg/m^2 and at least one weight-related health condition such as high blood pressure, sleep apnea, type 2 diabetes, or high cholesterol.
More than 40% of WNP participants succeeded in losing at least 5% of their body weight, contrasting sharply with less than 20% in the non-WNP group. Additionally, 22% of WNP participants lost at least 10% of their body weight, compared to less than 4% in the comparison group. These outcomes suggest the potential for wider application and testing of the WNP approach in larger clinical trials.
Currently, the WNP is accessible to all eligible adult patients receiving primary care through U-M Health clinics, serving as an entry point to a variety of treatment options. This programme is a part of an extensive array of weight management services offered across various U-M Health departments.
Dr. Dina Hafez Griauzde, the study’s lead author and an assistant professor of internal medicine at U-M Medical School, emphasised the programme’s foundation on safe and effective obesity care integration into primary care settings. This model promotes a collaborative team approach to evaluate patients, explore treatment options including cost considerations, and facilitate access to specialised care and follow-up.
Senior author Dr. Andrew Kraftson, an endocrinologist specialising in obesity medicine, highlighted the need for such programmes due to a shortage of obesity specialists. The WNP builds upon the successes of other chronic disease programmes by fostering a closer partnership between specialists and primary care providers. Notably, two-thirds of the current obesity medicine specialists also serve as primary care physicians.
Patients referred to the WNP consult with obesity specialists knowledgeable about the comprehensive treatment offerings at U-M Health, including community diabetes prevention programmes and understanding of insurance coverage. Following these consultations, specialists provide personalised treatment recommendations tailored to each patient’s medical needs, financial situation, and preferences.
The WNP team closely monitors progress and coordinates ongoing care, offering treatments ranging from specialised dietary plans and anti-obesity medications to weight loss surgery. The initial study tracked 132 people enrolled in the WNP and a matched group of 132 receiving usual care, studying their health outcomes over a year.
This extensive research, backed by funding from the National Institute of Diabetes and Digestive and Kidney Diseases and other grants, supports the feasibility and efficacy of integrating specialised obesity care within primary care frameworks, aiming to enhance overall patient outcomes in weight management.
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Poor muscle health in Individuals with obesity increases risk of early death, study finds
A pivotal study presented at the European Congress on Obesity (ECO) in Venice, Italy, from 12-15 May, 2024, has unveiled a stark correlation between suboptimal muscle health and an increased risk of premature death among individuals with obesity.
The research, carried out by a Swedish team on a UK cohort, established that individuals with compromised muscle composition were three times more likely to die during the study period compared to those with healthier muscle conditions. Dr. Jennifer Linge of AMRA Medical in Linköping, Sweden, spearheaded the research and shared compelling insights. “By examining muscle composition, we can predict which individuals with obesity are most at risk of early death in the forthcoming years,” Dr. Linge explained, highlighting the potential of muscle analysis as a predictive tool for mortality.
In recent years, weight loss has become a central strategy in managing chronic conditions such as type 2 diabetes and cardiovascular diseases. With pharmaceutical advancements, patients are now achieving significant weight reductions, previously possible only through surgical interventions. However, this brings to light concerns about possible detrimental effects on muscle health, including severe muscle mass loss and reduced mobility.
Dr. Linge elaborated on the complexities of muscle health in individuals with obesity, “Although individuals with obesity typically have more muscle mass, their muscles tend to be comparatively weaker. They also exhibit lower muscle quality, as well as reduced mobility and function.” She emphasised the importance of thorough muscle composition assessments, which consider both muscle quantity and quality, in evaluating the safety of rapid weight loss treatments, particularly for more vulnerable patients, such as those with sarcopenic obesity or advanced age.
The study also highlighted a critical gap in research concerning muscle health among populations with obesity, despite existing evidence from MRI studies that link poor muscle health with reduced functional performance, increased illness, and higher mortality rates in individuals with non-alcoholic fatty liver disease (NAFLD) and the general populace.
To address this, Dr. Linge and her colleagues utilised the AMRA Researcher software to analyse MRI scans from 56,109 participants in the UK Biobank study. They measured muscle volume and muscle fat, establishing a personalised muscle volume z-score to benchmark each individual’s muscle volume against the norm for their sex and body size.
From the extensive dataset, 9,840 participants—half of whom were men, with an average age of 64.4 years and a mean BMI of 33.5 kg/m²—were identified as having obesity and had comprehensive data on muscle composition. Of these, 2,001 (20.3%) exhibited adverse muscle composition. Over an average follow-up of 3.9 years, 174 participants died, predominantly from ischemic and hypertensive diseases.
The study findings indicated that neither low muscle volume z-score nor high muscle fat alone significantly influenced mortality risk. However, adverse muscle composition—characterised by both low muscle volume and high muscle fat—was strongly associated with a tripled risk of death during the follow-up period. This association persisted even when adjustments were made for factors like strength (hand grip), other diseases (cancer, type 2 diabetes, and coronary heart disease), and lifestyle factors (smoking, alcohol consumption, and physical activity), revealing a 70% increased risk of early death.
Sex, age, type 2 diabetes, and smoking were also noted as factors increasing the risk of premature death.
Dr. Linge concluded, “These results underscore the paramount importance of maintaining muscle health in people with obesity. It is crucial to determine whether drugs that achieve significant or rapid weight loss are inadvertently causing excessive muscle loss or worsening muscle quality, to ensure safer treatment approaches for obesity, particularly for those at greater risk.” This call to action not only emphasises the significance of maintaining muscle health but also the necessity of careful evaluation of treatment strategies for obesity.
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Adults using semaglutide as first obesity medication achieve greater weight loss, study finds
A recent study has indicated that adults commencing semaglutide as their initial treatment for obesity experience more substantial weight reduction compared to those who had previously used other obesity medications. This research, published in the journal Diabetes, Obesity and Metabolism, was conducted by Andres J. Acosta, MD, PhD, and his team at the Mayo Clinic in Rochester, Minnesota. It marks the first investigation into how prior use of anti-obesity drugs influences weight loss outcomes with semaglutide.
The retrospective cohort study analysed data from 305 adults treated at a Mayo Clinic centre from 2021 to January 15, 2023. Participants, who had an average age of 49 and were predominantly female (73%), received once-weekly subcutaneous injections of semaglutide (Wegovy, Novo Nordisk). The research team monitored body weight changes from baseline at 3, 6, 9, and 12 months after initiating treatment. Additionally, blood pressure and laboratory values were assessed at baseline and after one year.
Of those studied, 76% had not previously used any obesity medication before starting semaglutide, while 24% had used another obesity drug. Among the latter group, 28% had been treated with the GLP-1 receptor agonist liraglutide (Saxenda, Novo Nordisk), and 72% had used a non-GLP-1 obesity medication.
The findings revealed that those who were new to obesity medications and started with semaglutide saw a 14.3% reduction in body weight by 12 months, compared to a 10.6% decrease in those who had used other obesity treatments prior (P = .01). Despite similar proportions of both groups achieving at least 5% and 10% body weight loss, those new to obesity medication were significantly more likely to lose at least 15% (48% vs. 21%; P = .02) and at least 20% (27% vs. 4%; P < .01) of their body weight.
The analysis also showed a distinct pattern in weight loss during the first six months, where those without prior obesity medication use consistently lost more weight than those who had previously used liraglutide or other non-GLP-1 obesity drugs. By nine and twelve months, while weight loss among previous liraglutide users remained lower, those who had used other non-GLP-1 medications achieved similar weight loss to the semaglutide-naive group.
An interesting finding was that adults not previously on obesity medications exhibited a significant reduction in HbA1c levels at 12 months compared to their counterparts who had used such medications before (P < .001), although no other significant differences in metabolic outcomes were noted.
The study highlights a potential issue where prior usage of specific obesity treatments like liraglutide might lessen responsiveness to new medications such as semaglutide. The researchers suggested that these findings underscore the necessity for precision medicine in obesity management, advocating for treatment plans tailored to individual genetic backgrounds, environmental factors, and prior medication history to optimise effectiveness, reduce unnecessary drug exposure, and consider financial impacts on patients.
This study opens the door for further prospective research to explore and confirm the differential impacts of switching obesity medications and to enhance the understanding of optimal treatment strategies in obesity management.
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Melatonin offers new hope for obesity prevention according to recent studies
Recent collaborative research spearheaded by the University of Granada (UGR) has unveiled significant findings regarding the use of melatonin in the prevention of obesity. This research, conducted by a team comprising experts from UGR’s Department of Pharmacology, the Federico Olóriz Neurosciences Institute, the Biosanitary Institute of Granada, and the University of Qatar, has shown promising results in mitigating the risks associated with visceral obesity. This type of obesity is especially concerning as it involves fat accumulation deep within the abdomen, surrounding vital organs, thus posing heightened health risks.
The studies, which were led by Professor Ahmad Agil of UGR and published in the well-regarded journals Antioxidants and Biomedicine & Pharmacotherapy, employed a methodical approach to their experimentation. Using adult rats with obesity and diabetes of both sexes, the research demonstrated that chronic administration of melatonin at a dosage of 10 mg/kg of body weight per day over three months is significantly more effective in preventing obesity compared to short-term treatments. Notably, the treatment resulted in a reduction of visceral fat by approximately 3%. Moreover, the studies highlighted melatonin’s ability to alleviate muscle-fibre atrophy associated with obesity, transform muscle fibre types into a more oxidative and slower phenotype, and increase mitochondrial activity and content—factors which collectively contribute to the observed reduction in weight gain among the treated rats.
An intriguing aspect of the research involved combining melatonin treatment with exposure to slightly cold water, around 17°C, which simulates the average sea temperature. This combination was found to further enhance weight loss, suggesting a potential new approach to managing obesity in humans.
Professor Agil underscored the growing prevalence of obesity, overweight, and type 2 diabetes across both developed and developing nations. He attributed these conditions to poor adaptation of the human genome to current environmental factors that include sedentary lifestyles, consumption of hypercaloric diets, and exposure to persistent artificial light which disrupts natural circadian rhythms and reduces endogenous melatonin levels.
To counter these challenges, Professor Agil recommends several lifestyle adjustments based on individual circadian rhythms. During the day, he suggests exposure to natural light, engaging in physical activity, opting for low-calorie, unprocessed diets, and incorporating thermogenic spices in meals while avoiding snacks between meals and reducing the use of insulating clothing and heating in homes. At night, recommendations include sleeping in complete darkness, avoiding blue light-emitting devices before bedtime, and practising fasting to boost melatonin levels naturally. For older adults and those suffering from obesity, Professor Agil advises the administration of melatonin under medical supervision.
The overarching goal of these studies is to integrate strategies like melatonin administration and intermittent fasting into medical practices to address the complex challenges posed by ‘diabesity’—a confluence of diabetes and obesity—and its associated complications, such as hepatic steatosis, hypertension, and lipid disorders. The research builds on 13 years of prior studies which have consistently shown that pharmacological use of melatonin can serve as a viable strategy in treating central obesity and its related complications. Moreover, melatonin has been found to activate brown fat and enhance the conversion of subcutaneous fat to a more metabolically active form, thus promoting the formation of beige fat cells from mesenchymal stem cells in humans.
These findings not only reaffirm the potential of melatonin in treating visceral obesity but also highlight the necessity for further clinical trials to confirm its efficacy in human subjects. Encouraging results from existing human trials support the progression to more extensive studies focusing on melatonin’s role in maintaining mitochondrial homeostasis and potentially slowing or halting the progression of obesity and its complications through prolonged pharmacological use.
The research has received funding from the SAF2016-79794-R project of the Ministry of Science, Innovation and Universities and is also supported by the European Regional Development Fund (ERDF).
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Study reveals sweeteners do not elevate hunger while aiding in blood sugar reduction
In a groundbreaking research endeavour, the substitution of sugar with both artificial and natural sweeteners has been shown to not increase hunger levels in individuals, whilst also facilitating a reduction in blood sugar levels. This discovery comes from a rigorous double-blind randomised controlled trial, which observed that foods containing sweeteners do not lead to heightened appetite sensations or alter appetite-related hormone reactions compared to their sugary counterparts. Notably, this substitution offers additional advantages, such as the lowering of blood sugar levels, a crucial factor for individuals at risk of developing type 2 diabetes.
The incorporation of sweeteners as a sugar substitute in food products has sparked considerable debate, with prior studies providing inconclusive evidence regarding their potential to stimulate appetite. However, this recent study, adhering to the highest standards of scientific proof, delivers compelling evidence that sweeteners and sweetness enhancers do not adversely affect appetite. Moreover, they play a significant role in reducing sugar intake.
Conducted under the auspices of the University of Leeds in collaboration with the Rhône-Alpes Research Center for Human Nutrition, this study forms part of the extensive research undertaken by the SWEET consortium. Comprising 29 European partners from research, consumer, and industry sectors, the consortium aims to investigate the long-term benefits and possible risks associated with the transition to sweeteners and sweetness enhancers, focusing on public health and safety, obesity, and sustainability. The research received funding from Horizon Europe.
Catherine Gibbons, the study’s lead author and an Associate Professor at the University of Leeds’ School of Psychology, stressed the importance of reducing sugar intake in combating the escalating prevalence of obesity-related metabolic diseases like type 2 diabetes. She noted that removing sugar from foods without offering a substitute could potentially compromise taste and heighten cravings for sweet foods, thus making adherence to a low-sugar diet challenging. The substitution of sugars with sweeteners and sweetness enhancers in food products represents a prevalent dietary and food manufacturing strategy to diminish sugar consumption and enhance the nutritional value of commercial foods and beverages.
Graham Finlayson, Principal Investigator and Professor of Psychobiology at the University of Leeds, highlighted the scrutiny that the use of sweeteners and sweetness enhancers has attracted, including claims linking their consumption to adverse health outcomes. These reports have muddled public perception, particularly among those at risk of metabolic diseases, about the safety of these substances.
“Our study provides essential evidence supporting the daily use of sweeteners and sweetness enhancers in managing body weight and blood sugar levels,” Finlayson stated.
This pioneering study, a first of its kind, examined the impact of consuming biscuits infused with either sugar, the natural sugar alternative Stevia, or the artificial sweetener Neotame on a group of 53 adult men and women with overweight or obesity issues. Prior research on sweeteners and sweetness enhancers predominantly utilised beverages as a medium and seldom included participants with overweight or obesity or both sexes. Moreover, these studies usually focused on a single sweetener, primarily aspartame, against a control, with very few examining the effects of repeated daily consumption of a known sweetener or sweetness enhancer as part of a regular diet.
The trial, executed at the University of Leeds and the Rhône-Alpes Research Center for Human Nutrition in France between 2021 and 2022, involved participants aged between 18 to 60, all with overweight or obesity. It comprised three two-week consumption phases, with participants consuming biscuits containing different fillings: sugar, Stevia, or Neotame, with intervals of 14-21 days between each phase.
The initial and final days of these phases were conducted in a laboratory setting. Participants, after an overnight fast, provided blood samples to establish baseline glucose, insulin, and appetite-related hormone levels. They were also asked to evaluate their hunger and food preferences. Following the biscuit consumption, participants rated their fullness over several hours, and measurements were taken for glucose and insulin levels, along with ghrelin, glucagon-like peptide 1, and pancreatic polypeptide – hormones linked to food consumption.
The findings indicated no significant differences in appetite or endocrine responses between the sweetener types and sugar. However, insulin levels, measured two hours post-consumption, along with blood sugar levels, were observed to decrease.
Professor Anne Raben, joint co-ordinator of the SWEET project from the University of Copenhagen, Denmark, remarked, “The findings affirm that sweeteners are a beneficial tool in reducing the consumption of added sugar without triggering a compensatory increase in hunger or energy intake. This supports the effectiveness of sweeteners in managing appetite, energy, and weight.”
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