Team Metabolic Health

A novel 3D body shape method promises accessible and accurate body composition predictions, potentially transforming how we monitor health over time and detect risks.

In a recent study published in the journal npj Digital Medicine, researchers developed a novel method to predict body composition for three-dimensional (3D) body shapes. Body composition is linked to chronic disease risk. It can be assessed using computed tomography, dual-energy X-ray absorptiometry (DXA), and magnetic resonance imaging. However, due to ethical and practical constraints, these techniques are not readily available in epidemiological studies and clinical practice and are not easily accessible to the general public.

Conventional anthropometrics, such as waist-hip ratio, body mass index (BMI), and waist-hip circumferences, are used to infer body composition. Nevertheless, these methods do not differentiate between lean and fat mass and are inadequately accurate/convenient for longitudinal use, often requiring trained personnel and in-person visits. Thus, simple, accessible, inexpensive tools are needed to assess body composition accurately.

About the study

In the present study, researchers developed a novel method for body composition prediction using 3D body shape. They obtained DXA scans, metabolic health variables, and paired anthropometry data from the Fenland study established in 2005. The Fenland study involved 12,435 participants in Phase I and 7,795 in Phase II. Of these, 11,359 participants from Phase I and 6,102 from Phase II were included in the current study.

The team used 80% of Phase I data to train and derive 3D body shape composition models, and the remainder was used for validation. Phase II data were used as a test dataset for validation in a now older population. Moreover, a smartphone validation study was undertaken with 119 healthy adults, which, besides DXA scans, included air plethysmography and a mobile app capturing images. This sample was used to validate models derived from the Fenland study and assess the accuracy of 3D shapes obtained from smartphone images. Statistical validation metrics, including Pearson correlation coefficients and root-mean-square error (RMSE), were employed to measure the accuracy of these predictions.

Each three columns shows one participant who lost (Columns 1–3), maintained (Columns 4–6) or gained (Columns 7–9) fat mass, their DXA scans and fitted meshes for Fenland phase 1 (Row 1) and phase 2 (Row 2). Changes in body shape for the first and third participants are significant.

2D images of the front, back, right-side, and left-side profiles were taken using a purpose-built mobile app that constructs a 3D body mesh. The researchers fitted 3D body meshes to DXA silhouettes with paired anthropometry measures, and the fitted parameters were used for predicting body composition metrics. To fit a 3D mesh, DXA silhouettes were augmented with paired anthropometrics using the skinned multi-person linear (SMPL) model in a two-stage approach.

First, the hierarchical kinematic probability distributions (HKPD) method was used for initial pose and shape estimates. Next, an optimization method was developed to refine this initial guess. Optimized SMPL shape parameters were used to regress body composition metrics. A feed-forward neural network was constructed for regression, which used 10 SMPL shape parameters, height, weight, gender, and BMI as the input. The network outputs included total lean mass, total fat mass, etc. Further, the HKPD method generated SMPL avatars using multi-view information from smartphone images. A model was developed to predict regional and total body composition metrics using these methods. Its performance was evaluated using root-mean-square error values. The associations between predicted values and DXA measurements were assessed using Pearson correlation coefficients.

Findings

The smartphone validation study participants were younger, leaner, and lighter than those in the Fenland study. The researchers noted that the optimized meshes agreed with the DXA silhouette much better than the initial shape and pose estimates. In the Phase I sample of the Fenland study, correlation coefficients between DXA and predicted parameters were robust for all lean and fat mass variables. Similarly, correlation coefficients were strong for all variables in the Phase II sample.

In addition, comparable results were observed in the external validation sample. The Pearson correlation coefficients exceeded 0.86 for most metrics, indicating strong agreement between predicted and DXA values. Further, a comparison study was conducted on different regressor model inputs. One model, which used only height and weight as inputs, showed some predictive ability. Performance increased by including waist and hip circumferences, respectively. The final model, which used SMPL, height, and weight as inputs, showed substantial improvements in estimating body composition metrics. The model demonstrated a root-mean-square error (RMSE) of less than 3.5% for percentage body fat predictions, highlighting its accuracy.

In the Fenland study, 5,733 individuals participated in both phases, allowing for the evaluation of the model’s ability to detect changes in body composition over an average of 6.7 years. The model detected changes for various fat mass metrics; lean mass changes were less well captured, mainly because lean mass remains essentially unchanged over time.

Conclusions

The researchers introduced a novel computer vision-based method fitting a 3D body mesh to a DXA silhouette with paired anthropometric data and generated a database of 3D body meshes. These meshes accurately predicted body composition metrics. Moreover, the model could detect longitudinal changes. However, the researchers noted that while the model was particularly effective at detecting changes in fat mass, its ability to track changes in lean mass was more limited, due to the stability of lean mass over time.

The team also illustrated that avatars generated from smartphone images could be used for body composition prediction. Overall, 3D body shapes generated from 2D images and relevant inference methods could be a viable alternative for clinical medical imaging. The study acknowledges the demographic limitations of the dataset, which predominantly included white European adults, suggesting further research in diverse populations for broader applicability.

Credit: mews-medical.net

Team Metabolic Health

New trials reveal that the popular diabetes and weight-loss drugs Ozempic and Wegovy can offer even more health benefits.

These two injected drugs are versions of semaglutide. In multiple new data analyses, the drugs appeared to cut people’s odds for heart failure and its complications, reduce deaths from COVID-19 and lower deaths from any cause.

Semaglutide is a member of family of drugs called GLP-1 agonists, which work by mimicking the effect of a natural hormone that helps reduce appetite, hunger and food intake. 

The latest findings were presented Thursday in London at the annual meeting of the European Society of Cardiology (ESC) and published simultaneously in the Journal of the American College of Cardiology (JACC).

Credit: Dreamstime

The latest findings were presented Thursday in London at the annual meeting of the European Society of Cardiology (ESC) and published simultaneously in the Journal of the American College of Cardiology (JACC).

The data show that “these groundbreaking medications are poised to revolutionize cardiovascular care and could dramatically enhance cardiovascular health,” said Dr. Harlan Krumholz, JACC Editor-in-Chief and a professor of medicine at Yale University.

Some of the findings derive from sub-analyses of data from a major trial called SELECT, which included more than 17,000 people who were overweight or obese and had been diagnosed with heart disease, but not diabetes.

The trial was funded by semaglutide’s maker, Novo Nordisk, and in findings published in November it found that the 2.4 milligram (mg) dose of the drug cut the odds of heart-related deaths, heart attacks and strokes.

In the two new subset analyses from SELECT, data showed that people taking semaglutide had a lower odds for death from all causes, compared to people who got a weekly placebo injection.

Another SELECT analysis looked at differences in outcomes based on patients’ gender. It found that women appeared to gain more of a heart-health benefit from the drug compared to men, but that both sexes did see reductions in terms of heart-related events.

Semaglutide also appeared to help shield users from the worst effects of COVID-19.

In a SELECT study data analysis, obese or overweight people who were taking the drug were infected with COVID at rates similar to those who were on placebo.

However, if they did get COVID, they were less likely to die from the disease if they had been taking semaglutide, the research showed.

Another study presented at the ESC meeting and published in the JACC focused on a major killer, heart failure.

This time, researchers looked at data from the FLOW trial, published in May and also funded by Novo Nordisk. That trial involved more than 3,500 people with type 2 diabetes and chronic kidney disease who got semaglutide or a placebo and were followed for an average of nearly 3.5 years. It found lower rates of kidney-related death in semaglutide users.

However, having both type 2 diabetes and kidney disease can raise a person’s odds for heart failure, a condition where the heart loses its ability to efficiently pump blood.

The new subset analysis found that people in the FLOW trial who got semaglutide at the 1 mg dose had lower odds for new-onset heart failure or hospitalization for heart failure, compared to those getting the placebo injection.

In addition, three sub-studies of what’s known as the STEP-HFpEF program looked at the effect of semaglutide (2.4 mgs) among obese people with heart failure.

According to a JACC news release, “semaglutide improved heart failure-related symptoms, physical limitations and exercise function and reduced body weight” in all patients.

The drug also reduced levels of inflammation based on measurements of a common blood marker called C-reactive protein (CRP), and these reductions occurred regardless of weight loss, the study found.

Heart failure is often accompanied by the irregular heartbeat known as atrial fibrillation (A-Fib). The study also found “even greater improvements in heart failure-related symptoms and physical limitations in those with vs. without A-Fib, though improvements were seen in both groups,” according to the news release.

Finally, the heart failure study showed signs that use of semaglutide effected positive, healthy changes in the heart’s structure and function, based on echocardiogram results.

Overall, “this portfolio of publications, derived from three major trials, significantly advances our understanding of the wide-ranging benefits of GLP-1 agonists,” Krumholz said.

Credit: healthday.com

Team Metabolic Health

Research highlights the hepatic vagal nerve’s role in regulating food intake rhythms, offering new insights for potential anti-obesity treatments.

A recent Science study found that communication between the hepatic vagal afferent nerve (HVAN) and the brain influences circadian eating patterns. In mice, surgical HVAN removal corrected altered food intake and reduced weight gain from high-fat diets, suggesting HVAN could be a target for anti-obesity treatments.

Background

Circadian rhythms are 24-hour cycles regulating physical, mental, and behavioral changes in animals, typically aligned with light and dark cycles. While usually stable, these rhythms can be disrupted by changes in behavior or light exposure, as seen with jetlag or shift work, leading to desynchrony between organ systems.

The suprachiasmatic nucleus (SCN) serves as the master circadian clock, using light cues to establish feedback loops (TTFLs) of molecular-clock genes. Recent findings show that almost all somatic cells also maintain their own TTFLs, which help balance circadian rhythms with other processes, like food intake.

Synchrony between the SCN and food-entrained liver rhythms is crucial for maintaining metabolic balance amidst environmental changes. Studies in both rodents and humans suggest that desynchrony between these systems harms’ health, increasing the risk and severity of metabolic disorders like obesity and diabetes. However, the precise mechanisms and signals driving these interactions remain unclear.

Study: Hepatic Vagal Afferents Convey Clock-Dependent Signals to Regulate Circadian Food Intake. Image Credit: alexkich/Shutterstock.com

About the study

The present study investigates the mechanisms of circadian rhythm-establishing communication between the liver and the brain by deleting REV-ERBα/β nuclear receptors in murine model systems.

These nuclear receptors have previously been identified as central regulatory components of chrono-metabolic homeostasis. Consequently, their deletion induces desynchrony.

Contrasting previous investigations in the field, researchers used tail vein injections of REV-ERB deletion-capable adenoviruses, providing the present study with the unique advantage of location-specific (rather than system-wide) clock disruptions.

Specifically, this study methodology allowed for the observation and manipulation of asynchrony between the liver and the brain while leaving other organ systems unaltered, thereby substantially reducing background noise and confounding results.

Surgical and experimental interventions were carried out on three different cohorts of adult laboratory mice – C57Bl/6J, Nr1d1fl/fl/Nr1d2fl/fl, and Arntlfl/fl.

Outcomes under investigation include changes in gene expression between control (sham surgery) and case (HepDKO) mice and comparisons between their respective body weight gains during the study period.

The study additionally focused on the role of the hepatic vagus nerve (HV) in brain signaling and weight modulation. While previously known to serve as a transmission center for supplying the brain with liver metabolic data, HV’s explicit role in circadian communication and food intake rhythms remains hypothetical.

The present study explores HV’s role via the surgical removal of surgical ablation of HV in case mice and the subsequent comparisons of their weight gain with controls under diet-induced obesity (DIO) conditions.

Study findings

The present study emphasizes the role of food intake as a zeitgeber (an external cue that synchronizes biological rhythms) for circadian modulation in the liver, similar to how light-dark cycles serve as the zeitgeber for SCN-driven circadian rhythms across the body.

This means that daily cycles of hunger and satiation don’t necessarily need to match light-dark cycles; each rhythm operates independently based on its cue (food or light), with liver-brain communication maintaining balance between them.

In gene knockdown mouse models, deleting REV-ERBα and REV-ERBβ nuclear receptors disrupted food intake rhythms without affecting SCN-regulated cycles.

This deletion activated clock genes Arntl and Per2, known for their role in chrono-metabolic balance, leading to altered food intake patterns and increased eating during light periods, ultimately causing significant weight gain. Interestingly, severing the hepatic vagal afferent nerve (HVAN) reversed these effects, reducing food intake and resulting in weight loss.

This highlights HV’s crucial role in brain signaling for food-driven rhythms, with parallel studies showing contrasting outcomes: activating gut signaling afferents in humans led to weight loss, underscoring the complexity of gut-brain interactions in metabolic regulation.

Conclusions

The present study used murine model systems to identify the mechanisms underpinning chrono-metabolic homeostasis and corresponding food intake dysregulation.

Study findings revealed that the HV serves as a communication and signaling center, informing the brain of alterations in food intake rhythms detected via REV-ERBα/β nuclear receptors. This signaling results in increased light-cycle food intake and substantial weight gain.

Ablation of the HV was observed to reverse these effects, pinpointing it as a target in future weight loss research.

Credit: news-medical.net

Team metabolic Health

Amgen (AMGN.O), has said that there was no link between its experimental weight-loss drug and changes in bone density, a day after those concerns wiped off more than $12 billion from the company’s market value.

The drugmaker’s stock slumped 7% on Tuesday after analysts at Cantor Fitzgerald said their review of early-stage data on Amgen’s MariTide showed a drop in bone mineral density, which can increase the risk of fractures.

But Amgen said “the Phase 1 study results do not suggest any bone safety concern or change our conviction in the promise of MariTide.” It plans to report data from its mid-stage study later this year.

Amgen’s shares rose 1.8% in early trading.

Investors are keenly awaiting more data on a drug seen as a contender in the estimated $150 billion market for weight-loss treatments.

Amgen shares react to obesity-drug

Cantor analysts said they found the bone mineral density changes when reviewing supplemental data that was published along with the results in February.

But at least four analysts said the concerns were overblown, since the company was conducting a mid-stage study and planned a larger late-stage trial.

A new safety signal would certainly cause alarm, but Amgen knows much more about MariTide than Wall Street, Piper Sandler analyst Christopher Raymond said in a note.

MariTide activates the GLP-1 hormone associated with the feeling of fullness, similar to popular weight-loss drugs such as Novo Nordisk’s (NOVOb.CO), Wegovy and Eli Lilly’s (LLY.N), Zepbound. MariTide also blocks the activity of another gut hormone called GIP, which has been linked to fat storage.

Amgen, one of the several companies developing weight-loss drugs, hopes the different approach will provide quicker weight loss and less frequent dosing compared to Wegovy and Zepbound.

MariTide cut weight by 14.5% in the 49-patient early-stage trial, according to the data, published in Nature Metabolism journal in February.

Credit: Reuters

Team Metabolic Health

A new study finds that empowering communities with systems-based tools to fight childhood obesity not only reduced weight trends but also improved quality of life in boys—suggesting a resilient, community-first approach to lasting health changes.

The RESPOND randomized trial is a community-based systems intervention to prevent childhood obesity and non-communicable diseases.

Scientists at Deakin University recently evaluated the trial’s three-year behavioral, health-related quality of life, and body mass index outcomes. The study is published in the journal Public Health.

Background

Childhood obesity is a serious public health concern as it often persists into adulthood and increases the risk of several non-communicable diseases.

The complex and multifactorial nature of childhood obesity risk factors may lead to resistance to intervention. This complexity includes multiple factors that can influence a child’s food consumption, including early-life exposure to a variety of foods, food availability at home and within the community, and socioeconomic status.

Existing evidence indicates that multi-level interventions that apply multiple strategies across communities can significantly reduce children’s body weight.

Systems science and systems thinking are methods of understanding the relationships and connections between component factors driving complex systems. Thus, they can provide promising and innovative interventions to prevent childhood obesity.

The Reflexive Evidence and Systems Interventions to Prevent Obesity and Non-communicable Disease (RESPOND) trial was initiated to examine whether building the capacity of key community health staff at scale through systems-based training can develop a sustainable model for delivering such interventions for childhood obesity prevention.

In this study, scientists have evaluated the impact of the RESPOND trial on BMI z-scores (standardized body mass index), health-related quality of life, and related behaviors.

Study: Three-year behavioural, health-related quality of life, and body mass index outcomes from the RESPOND randomized trial. Image Credit: chanchai plongern/Shutterstock

Study Design

RESPOND was designed as a four-year randomized childhood obesity prevention trial involving 10 local government areas in northeast Victoria, Australia. The aim was to build community capacity to apply systems science to prevent childhood obesity and non-communicable diseases.

The intervention was initially implemented in the selected areas in July 2019 (step one) or July 2021 (step two). Baseline child-level data were collected between March and June 2019, and the follow-up data collection was planned for 2021 and 2023.

Due to the COVID-19 pandemic, however, step two communities could not begin their intervention as planned and were therefore treated as controls.

The step one communities partially implemented the intervention actions and were defined as “intervention communities.” The trial was altered to a cluster-parallel randomized design, allowing the researchers to compare outcomes in intervention and control communities.

In this study, scientists compared intervention versus control communities over three years (2019–2022). The study analyzed data obtained from 31 primary schools that participated in both March to June 2019 and March to August 2022 data collection waves.

The three-year outcomes included BMI z-scores, health-related quality of life, and self-reported health behaviors.

Important Observations

The analysis conducted within intervention communities revealed a small reduction in BMI z-scores and the percentage of overweight or obesity from 2019 to 2022. Within control communities, a small increase in BMI z-scores and the percentage of overweight or obesity was observed during the same period.

Self-reported health behaviors revealed limited effects of the intervention on any analyzed outcomes (physical activity, recreational screen time, and frequency of takeaway food consumption). However, a noteworthy intervention effect on daily water consumption was observed in boys.

Between 2019 and 2022, overall health-related quality of life deteriorated for children, likely due to COVID-19-related challenges. However, for boys, a significant improvement in quality of life and psychosocial health was observed within intervention communities.

Study Significance

The study finds a limited but positive effect of the community-based systems intervention (RESPOND) on psychosocial health, overall quality of life, and water consumption among boys who participated in the trial. However, the intervention had no significant impact on these metrics for girls.

The study also finds a general decline in several obesity-related behaviors among boys and girls in both intervention and control communities over the study period, which researchers attribute in part to the pandemic’s impact on lifestyle behaviors.
A non-significant but favorable effect of the intervention has been observed for BMI z-scores, overweight or obesity prevalence, and several other behavioral outcomes (active transport to and from school, sleep, and consumption of takeaway food and sweetened drinks).

The RESPOND trial utilized systems thinking to help communities identify and target local childhood obesity risk factors. The researchers emphasize that understanding these local factors is crucial in assessing the intervention’s overall merit.

The findings suggest that empowering communities to use systems thinking in obesity prevention could have a protective effect on children’s health, even in the face of major challenges like the COVID-19 pandemic.

Given the scarcity of effective interventions to address childhood obesity and non-communicable diseases, building capacity within communities to deliver systems-based interventions seems to be a promising approach.

Further analyses and investments in RESPOND’s findings could lead to broader training of community health workers in systems thinking and enable the creation of a learning system for effective and rapid knowledge acquisition. Further investigation is also needed into the observed gender differences in intervention effects.

Credit: news-medical.net

Team Metabolic Health

Smart guide on which variety to look out for and how to have it

Have you been buying packaged millets from shop shelves thinking you are making a healthy choice? Chances are they are polished millets which could be spiking your sugar levels just like any other carbohydrate. While polished millets bring down the cooking time and ease digestion, they also lead to the loss of minerals and phytochemicals that make them healthy. Debranning — or removing the outer layers of the grain — also makes them starchy and high in glycemic index, according to Dr Shobana Shanmugam, head of the department of diabetes food technology at Madras Diabetes Research Foundation.

Millets cooked like rice are preferable to chapatis made of millets as they hold more moisture and are easier to eat. (File)

“Integrating different millets into the diet — instead of wheat and rice — can help in increasing food diversity. This is essential for combating the triple burden of malnutrition in India — undernutrition, overnutrition, and micronutrient deficiency. But debranning reduces food value,” she says. Her team recently published a paper in the journal Springer Nature on the impact of debranning on five Indian millets — foxtail, little, kodo, barnyard, and proso.

What happens when millets are debranned or polished?

Debranning leads to loss of minerals — iron, calcium, zinc, phosphorus, magnesium — in all five millets. “In fact, iron levels went below the level of detection in the grains in our studies,” says Dr Shanmugam. The process also led to the loss of protein content in all but two of the millets — little and barnyard millets. These are likely to contain the protein in the inner layers.

Significantly, the available carbohydrate went up across all five millets when polished by up to 11 gm per 100 gm of the millet. “We looked at the grains with electron microscopy to check which are the layers that have been removed. And, higher the degree of polish, the more starchy the grain becomes,” says Dr Shanmugam.

“While there is awareness that millets are better for your health, people might not know that these grains too can be polished. And, that the process can remove a lot of the nutrients. Yet, many polished millets make health claims that can be misleading,” she warns.

How can one tell whether the millet has been polished?

Dr Shanmugam suggests a few ways one can tell whether a grain has been polished or not:

1) Polished grains look whiter than the unpolished ones, which are dull.

2) Two, the grains should be glassy because of the oil content in the outer layers.

3) The polished grains are likely to be smoother to touch while the unpolished ones are rougher.

How can millets be integrated into our diets?

Millets cooked like rice are preferable to chapatis made of millets as they hold more moisture and are easier to eat. “If you see rice, it expands quite a bit when cooked. Around 70 per cent of the rice we eat is water; chapatis are the opposite and will have about 30 per cent water.”

Bottom of Form

She also warns against diabetics eating porridge made of millets. “When we make millet porridge, it again increases the glycemic index and can raise blood glucose levels.”

Credit: The Indian Express

Team Metabolic Health

Most people know that losing weight has numerous benefits, but making major lifestyle changes can be extremely difficult. For example, obese people are often at risk for injuries when they start a new exercise routine, which can set them back or ultimately cause them to give up on it. As a result, more and more people have been turning to weight loss medications for help.

In the last couple of years, a new class of weight-loss injection drugs called GLP-1 agonists like semaglutide, tirzepatide, liraglutide and dulaglutide has made headlines for their promise to help people lose weight. The drugs go by several different brand names, and more are being approved all the time. But what are they, how do they work and are there things current cancer patients should be aware of if they’re considering these drugs?

For answers to these questions, we talked to endocrine neoplasia and hormonal disorders specialist Sonali Thosani, M.D.

How do these drugs work, and how are they different from previous weight loss drugs?

Previous weight loss drugs worked in a few different ways. Some suppressed appetite and made you feel fuller longer, but these could only be used for a limited time due to the side effects. Others inhibited fat absorption, but were hard to tolerate for many patients because they caused gastrointestinal issues.

This new class of drugs, the GLP-1 agonists, has been used for diabetes treatment since 2005, but they only have gotten approval for obesity treatment in the last decade. They work by slowing down gastric emptying. This makes patients feel fuller longer, helping them eat less. They also help balance blood sugars after eating by stimulating insulin secretion and inhibiting glucagon secretion.

Studies have shown that patients can lose up to 20% of their body weight with GLP-1 agonists. That makes these drugs comparable to surgical options, like gastric sleeve surgeries. However, they also have some side effects, with many patients experiencing nausea, vomiting and diarrhea. There have also been some recent reports that they might be linked to gastroparesis in some patients. This is a paralysis of the stomach that can be debilitating and hard to treat.

What’s also interesting about these drugs is that GLP-1 is a neuropeptide. This means it’s made in the neuronal cells in the brain and released in the hypothalamus, which controls several metabolic and cardiovascular functions. So, it will be interesting to see what we continue to learn about how these drugs work and what the long-term effects might be on other organ systems.

Can weight loss injections decrease your cancer risk?

This is a more complicated question than it seems because obesity is so closely associated with increased cancer risk. There are really two questions here:

Do the drugs themselves decrease cancer risk?

Does their ability to decrease obesity result in a lowered cancer risk?

There is significant evidence that the answer to the second question is yes, with the caveat that patients should know that these drugs aren’t meant to be taken forever. Many people take GLP-1 agonists or other weight loss medication, they lose weight, they go off the drugs and then they gain the weight back. That’s not going to help lower long-term cancer risk.

Where these types of drugs can be helpful is that many obese people have a hard time making healthy lifestyle changes because it’s very difficult for them to exercise. If taking these drugs for a limited amount of time can help some lose weight quickly so they can get on an exercise plan they can stick to, then that’s helping lower cancer risk long-term. But it all comes back to the person making and sticking to those lifestyle changes, even after they stop taking the drugs. If they can do that, then you’re probably seeing a net positive about long-term cancer risk or other long-term health risks.

As for whether the drugs themselves reduce cancer risk, it’s too early to say for sure. But there is some evidence that GLP-1 agonists like semaglutide may decrease cancer risk beyond just their ability to help people lose weight. A study published early this year showed that patients with diabetes who used weight loss injections were less likely to have colorectal cancer compared to patients on other diabetes drugs, regardless of whether the patients were overweight.

Are there concerns that weight loss injections could increase cancer risk?

There was an early study a couple of years ago that indicated a possible link to thyroid cancer, but that study had some limitations, and subsequent studies have shown that there is likely not a link there. The European Medical Agency even announced that they did not find a causal link after a months-long review of the data.

There has also been some concern that some of the side effects could increase the risk of pancreatic cancer, but so far, studies have not shown that to be the case.

If cancer isn’t a major concern, are there other concerns about these drugs?

There’s always a bit of wariness when a new class of drugs comes to market because we’ve seen several times where promising drugs came to market for weight loss and then they’ve had to be pulled back, due to safety concerns. What’s unique about GLP-1 agonists compared to other weight loss drugs is that we already have a lot of experience with them in patients with diabetes. We also know from the published data that these drugs have heart health benefits; this sets them apart from other weight loss drugs currently on the market.

The primary concern is the availability of these drugs for the patients who need them. They’re expensive, and it’s been hard to get insurers to cover them, even when a patient has a clear indication for them. And there are celebrities and influencers using them who don’t have indications for their use, adding to a national shortage and making them even harder to get.

And the gastroparesis issue is not a small thing. Doctors need to be selective when deciding whether a patient meets the criteria for these drugs because gastroparesis can be very difficult to manage. Guidelines from anesthesia and surgical societies recommend holding the weekly formulations of these drugs for at least a week before surgery, so careful planning is required if a patient is using these therapies.

Are there concerns about these drugs for people who have already had cancer?

There are a couple of things to note for cancer patients, which is why it is always very important to discuss these things with your care team.

We generally avoid GLP-1 agonists for pancreatic cancer patients, for example, because these patients are already at high risk for pancreatitis, and these drugs do carry some potential risk for that. We are also cautious about using these drugs if you’re on active cancer therapy and experiencing side effects such as nausea and vomiting; GLP-1 agonist therapy can sometimes worsen those.

These drugs cause dramatic weight loss, some of which is also a significant muscle mass loss. So, we need to carefully monitor their use in patients who are on active chemotherapy, as sarcopenia and weight loss can make it harder for patients to tolerate chemotherapy.

Are there alternatives to weight loss drugs that people should consider?

I think bariatric surgery is underutilized. And, of the 20 million adults in the US who suffer from severe obesity, less than 1% will undergo bariatric surgery annually. There was a study presented at a national meeting looking at the role of bariatric surgery in patients with obesity and the impact on cancer prevention, and it found a marked decrease in cancer diagnoses in patients with obesity who underwent bariatric surgery compared to those who didn’t. This was really the first study to address this question, and I think this exciting new area will have more studies coming out in the next 10 to 15 years.

Credit: mdanderson.org

Team Metabolic Health

Restricting new fast-food sellers in areas where there are already a large number could reduce obesity and overweight in children.

In a recent study published in obesity, researchers investigated whether a policy in England that banned new fast-food outlets effectively reduced obesity and overweight in children.

Their findings indicated that restricting new fast-food sellers in areas where there are already a large number could reduce obesity and overweight in children.

Study: Planning policies to restrict fast food and inequalities in child weight in England: a quasi-experimental analysis. Image Credit: Paulo PFZ STUDIO/Shutterstock.com

Background

The United Kingdom has among the highest rates of childhood obesity in Europe, with obesity among ten and 11-year-olds increasing from slightly under 32% in 2006-07 to nearly 41% in 2020-21. The pandemic is thought to have been one of the drivers for this change.

Childhood obesity is associated with several short-term and long-term effects. In the short term, it reduces life quality and is linked to depression, anxiety, stigma, bullying, and self-esteem issues.

In the long term, childhood obesity can continue into adulthood and increase the risk of mental disorders, diabetes, and cardiovascular diseases. The cost of obesity-related conditions for the National Health Service was estimated to be £6.1 million in 2015, and this is expected to rise to £9.7 billion by 2050.

Complex factors influence obesity, but environmental factors, especially outside the home, play a major role. Fast food intake and the density of fast-food outlets have been linked to higher energy consumption and obesity, particularly in low-income areas.

The density of fast-food outlets in England has increased from 142 per 100,000 residents in 2019 to 170 in 2021. The impacts are unequally felt, as deprived areas contain five times more outlets than wealthier areas.

In recent years, half of local governments have introduced planning guidelines that target limits on new outlets and promote healthier food environments. Gateshead, among the most deprived areas, implemented stricter planning policies to reduce childhood obesity.

A complete ban on new fast-food outlets since 2015 aimed to lower obesity in 10 and 11-year-olds from 23% to less than 10% by 2025. Studies show a reduction in fast-food outlets in Gateshead compared to areas without similar policies.

About the Study

In this study, researchers investigated whether reducing fast-food outlets leads to changes in childhood obesity and reduces health inequalities, exploring the impact of the policy within five years and whether it is more effective in deprived areas with high fast-food outlet density.

They gathered data on children’s weight and food outlets from national monitoring programs, also including population size and area-level deprivation indices, with higher scores indicating more deprivation.

The outcome variable was the prevalence of obesity and overweight in 10 and 11-year-old children, while outlet density was calculated as the number of outlets for every 100,000 residents in each area.

For the analysis, researchers considered areas in Gateshead to be the treatment group and matched them to areas from nearby regions that did not implement similar restrictions.

They then used statistical models to analyze the impact of restricting fast-food outlets, controlling for deprivation scores.

Findings

Areas in Gateshead had a consistently higher prevalence of obesity and overweight among children aged 10 and 11 compared to the control areas. Gateshead also had a higher density of fast-food outlets compared to control areas throughout the years.

The prevalence decreased from 38% in 2011 to 35.5% in 2015 but rose again to 37.7% by 2020. Over time, the difference in prevalence between Gateshead and the control areas narrowed.

The impact of planning guidance on reducing obesity and overweight prevalence was not statistically significant overall, but area-level deprivation scores did show a strong effect.

Notably, the planning policy had a significant reduction in obesity and overweight prevalence in the second and third-most deprived areas. This effect remained for the second most deprived area after sensitivity analysis.

Conclusions

The study provides evidence of the effectiveness of local planning policy in reducing obesity and overweight in children aged 10 and 11 within four years of implementation. There was a 10% reduction in fast-food outlet density in Gateshead within four years of the policy. 

Decreases in prevalence were observed in the second most deprived areas, which also had the highest concentration of fast-food outlets before the policy.

Researchers found no effects at the population level and noted that the effect could take longer than four years to be measurable.

These findings have policy implications, indicating that planning policies could help reduce inequalities in childhood obesity and overweight, relying on a structural approach to improve health outcomes rather than relying on changes in individual behavior.

However, the growing presence of online food delivery needs further research to understand its impact on access to unhealthy food and whether current policies need updates to address the changing food environment.

Credit: news-medical.net

Team Metabolic Health

Ozempic, prescribed for adults with type 2 diabetes, comes with serious drawbacks, while being valued for its benefits. Find out if Ozempic is worth it?

Ozempic | Image: iStock

Usually used to lower blood sugar levels in individuals with type-2 diabetes, Ozempic is back on the lips of medical experts after a recent study revealed the possibility of semaglutide, the active ingredient in Ozempic and Wegovy, proving effective in reducing the risk of Alzheimer’s in patients with Type 2 diabetes.

These recent revelations published in Alzheimer’s & Dementia support the nuero-protective benefits linked with GLP-1 receptors agonists. Ozempic has also been utilised to combat cardiovascular issues such as stroke and heart attack in people suffering from type 2 diabetes.

Benefits of Ozempic

The presence of GLP-1 receptors in the brain suggests that activating these receptors may offer neuroprotective effects, potentially aiding in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. A study in Nature noted that GLP-1 agonists can decrease inflammation in brain tissue, which is crucial since chronic inflammation is linked to cognitive decline.

Stable blood sugar levels are vital for mental well-being. Fluctuations in blood glucose can lead to mood disturbances, fatigue, and irritability, increasing the risk of anxiety and depression. By mitigating these spikes, Ozempic may indirectly enhance mood and cognitive clarity.

Credit: Republic World

Team Metabolic Health

Alzheimer’s causes a gradual decline in memory, thinking, behaviour, and social skills, and it is the most common cause of dementia.

According to the new study published in the journal Alzheimer’s & Dementia on Thursday, semaglutide was found to significantly lower the risk of developing AD compared to other diabetes medicines. Specifically, it was found to reduce the risk of a first-time Alzheimer’s diagnosis by 40% to 70%.

Semaglutide, the active ingredient in popular blood sugar control and weight loss drugs such as Ozempic and Wegovy, can reduce the risk of Alzheimer’s disease (AD) in people with type 2 diabetes, a new study shows.

Alzheimer’s causes a gradual decline in memory, thinking, behaviour, and social skills, and it is the most common cause of dementia. According to the new study published in the journal Alzheimer’s & Dementia on Thursday, semaglutide was found to significantly lower the risk of developing AD compared to other diabetes medicines. Specifically, it was found to reduce the risk of a first-time Alzheimer’s diagnosis by 40% to 70%.

“These results were similar for older patients, both genders, and those with and without obesity. Cumulative incidence curves [of semaglutide and other diabetes medicine] began to diverge within 30 days, and continued to separate thereafter, indicating semaglutide’s potential to delay or slow Alzheimer’s Disease development with sustained effects,” the study said.

A promising study

Researchers analysed health records of over a million patients in the US with type 2 diabetes to see how semaglutide affects the risk of developing AD. They compared semaglutide to seven other diabetes medications, and tracked the patients for up to three years to see if they were diagnosed with Alzheimer’s. The other diabetes drugs used in the study included metformin, insulin, and older GLP-1 drugs like liraglutide.

Using specific statistical methods, they studied the time it took for Alzheimer’s to be diagnosed in these patients, if at all. The study found that patients prescribed semaglutide had a significantly lower risk of AD than those who had taken one of the seven other diabetes drugs.

The most notable difference with regards to AD incidence was seen between patients who took semaglutide and those who took insulin, with semaglutide patients boasting a 70% lower risk of developing Alzheimer’s.

Semaglutide also outperformed its predecessor liraglutide. The study’s senior author Rong Xu, the director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University School of Medicine in Ohio, speculated based on this finding that more potent GLP-1 RA drugs might have an even stronger effect in combating Alzheimer’s.

“If there is a higher dose form, are we going to see an even stronger effect?” Xu said in an interview to NBC.

Science behind findings

The study said GLP-1 RAs, a group of drug which includes semaglutide, might help protect brain function. Early research on semaglutide identifies a number of ways in which it might benefit the brain such as lowering toxic effects of certain proteins linked to AD, improving how brain cells use glucose for energy, and reducing the buildup of harmful plaques and tangles associated with Alzheimer’s.

“Semaglutide reduces neuro-inflammation, which is commonly linked to Alzheimer’s. It helps stabilise blood sugar levels, limiting oxidative stress or cell damage and enhancing cellular energy. This action can protect neurons from degeneration, a hallmark of Alzheimer’s and other neurodegenerative diseases,” Dr (Prof) M V Padma Srivastava,  chairperson, Neurology, Paras Health, Gurugram, told The Indian Express.

“The study adds to our understanding of how blood glucose control via GLP-1 may offer brain-protective effects…[and] shows that effective blood glucose management and inflammation control are critical in Alzheimer’s progression,” she said.

Potential implications

The US Food and Drug Administration (FDA) has approved two treatments — Biogen’s Leqembi and Eli Lilly’s Kisunla — that marginally slow the progression of AD by targeting the disease’s hallmark amyloid plaques in the brain. But these can cause serious side effects, including brain swelling and brain bleeding. Traditionally, Alzheimer’s has been managed largely using cognitive and lifestyle interventions.

This is what makes the latest research, which introduces a new therapeutic pathway for treating Alzheimer, potentially ground-breaking. “By demonstrating that GLP-1 drugs can mitigate some risk factors for Alzheimer’s, the study suggests a dual-purpose use for these drugs: managing diabetes and offering a preventive mechanism for dementia,” Dr Srivastava said.

For India, this is particularly significant. The country boasts among the highest global rates of type 2 diabetes, which is associated with a higher risk of cognitive decline. This is because type 2 diabetes results in chronic insulin resistance, higher levels of inflammation, oxidative stress in the brain — all of which lead to impaired glucose metabolism in the brain, resulting in cognitive decline and neuron damage over time.

Bottom of Form

“GLP-1 drugs can delay or reduce dementia symptoms in diabetic patients, thus offering a preventive strategy where few currently exist,” according to Dr Srivastava. “Since Alzheimer’s rates are also rising among India’s ageing population, this research could be transformative,” she said.

Credit: The Indian Express

Team Metabolic Health

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Credit: PBS News

Team Metabolic Health

Models suggest societal upheaval from anti-obesity medicines — but impacts are hard to predict.

Welcome to the healthier, happier world of 2030. Heart attacks and strokes are down 20%. A drop in food consumption has left more money in people’s wallets. Lighter passengers are saving airlines 100 million litres of fuel each year. And billions of people are enjoying a better quality of life, with improvements to their mental and physical health.

These are just some of the ways in which analysts forecast that the new wave of incredibly effective weight-loss drugs, known as GLP-1 agonists, might transform societies and save countries trillions of dollars in the long run. The best known is semaglutide, marketed as Ozempic for diabetes, and as Wegovy for weight loss. “Short of some crazy unfortunate side effect, this is going to change the world,” says Chin Hur, a gastroenterologist at Columbia University in New York City.

Illustration: Karol Banach

It might have already started. In the United States, where 12% of adults say that they have at some stage taken GLP-1 agonists for diabetes or weight loss (see ‘Uptake of GLP-1 drugs in the United States’), media reports suggest that obesity rates are falling, although scientists caution that the data are not statistically significant (see ‘US obesity rates’). Slowing or reversing obesity trends more widely — more than half of the world’s population is expected to be overweight or have obesity by 2035 — would have myriad ripple effects. “The spillover impacts of obesity are enormous,” says Alison Sexton Ward, an economist at the University of Southern California in Los Angeles.

Source: KFF & US NCHS/CDC

But although scientists agree that the drugs could have huge impacts, there is a lot of uncertainty. Efforts to model the weight-loss drugs’ future impact are highly speculative for various reasons, ranging from their high costs to their long-term biological effects, and the big unknown of how people’s behaviour will change. All that has medical researchers and companies scrambling to gather more data and develop better tools to assess how weight-loss drugs might transform societies.

Source: KFF & US NCHS/CDC

Modelling a miracle intervention

Modelling obesity — and its prevention — has long been a staple of public-health research. One way of doing so is to create algorithms that simulate interventions, such as a tax on sugary drinks, or mandatory exercise programmes in schools. By shifting variables such as people’s willingness to cooperate or societal demographics, such models can estimate the health problems that would be prevented or the money that would be saved.

Such policy-based behavioural interventions usually have little effect on preventing weight gain or causing weight loss in the real world, at least in the short term. But the GLP-1 drugs could be different, says Theo Vos, an epidemiologist at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle. Trials show that drugs such as semaglutide allow people to lose around 15% of their body weight in 16 months. Next-generation drugs could be even more effective. “This really works, and it works in quite a dramatic way,” says Vos.

The easiest things to model are the immediate impacts of a drug for an individual, including improvements both for physical ailments, such as reduced sleep apnoea, heartburn or joint pain, and in mental health, such as experiencing less social stigma. “If you lose weight, your quality of life improves immediately,” Hur says. Clinical trials suggest that the drugs seem to treat a host of other conditions, too, including addiction, Parkinson’s disease and infertility, but Hur says that it’s still too early to incorporate these benefits into models.

Why do obesity drugs seem to treat so many other ailments?

GLP-1 agonists do have downsides: many users experience nausea, gastrointestinal problems or muscle atrophy, and when people stop taking the drugs, they tend to quickly put the weight back on. Still, GLP-1s are probably different from previous ‘miracle’ weight-loss drugs such as fen–phen (fenfluramine/phentermine), which was banned because of its severe side effects, says Nicolas Rasmussen, a science historian at the University of New South Wales in Sydney, Australia. GLP-1s have been used to treat diabetes for many years and seem to be safe for most people.

Nevertheless, Rasmussen says, “history does tell us they’ll be overused”. Although the drugs might be clearly beneficial for people whose obesity is harming their health, people who take them simply to lose a few kilograms must set that benefit against the side effects. That hasn’t seemed to slow demand, especially as social-media influencers and celebrities promote the drugs for weight loss. Pharmaceutical companies that produce some of the key drugs have experienced shortages.

Economic forecasts

Beyond the effects on individuals, researchers expect that wide use of GLP-1 drugs could have some startling broader economic impacts. Analysts project that a global market already worth US$47 billion this year will grow ten-fold by 2032. People in certain industries, such as the food sector, are already becoming worried by the popularity of the drugs. An analysis by US investment firm Morgan Stanley predicted that US calorie consumption could drop by 1.3% by 2035. Last October, John Furner, the chief executive of retail company Walmart U.S., said that the company had seen a drop in food sales that it attributed to weight-loss drugs. Some analysts have projected less-obvious effects. US investment firm Jefferies predicted for one US airline that, if every passenger flying with it lost roughly 10 pounds (4.5 kilograms), the airline would save more than 100 million litres of fuel per year. Other reports found potential impacts for companies producing medical devices such as knee implants for arthritis or masks for sleep apnoea, more demand for smaller cars, and reconfiguration of land and building use if people walk more in commercial areas.

On a global scale, the ripple effects on economies could be even greater. For instance, studies suggest that young people with obesity perform worse in school1 and that girls are less likely to go on to pursue higher education than their non-obese counterparts are2, even when controlling for factors such as race, income and parents’ socioeconomic level or education. Obesity-related health problems have also been shown to lead workers to take more sick days — which in turn can lead to workplace discrimination.

Costs such as these account for more than 2% of global gross domestic product (GDP), according to a 2022 report on obesity rates in 161 countries3. If the rate of obesity increase was suddenly slowed by 5% relative to current trends, the report found, countries would save more than $429 billion each year between 2020 and 2060. Such analyses do not try to model the costs of drugs or any other intervention that could lead to lower obesity rates.

Unclear consequences

But when it comes to GLP-1 agonists, some of these predictions might be premature, says Ross Hammond, a systems scientist at the Brookings Institution, a think tank in Washington DC, because weight loss with GLP-1 agonists might not directly translate into global cost savings and health improvements. “I’d be very uncomfortable saying the cost estimates [in those studies] are costs that could be saved by everyone being on Ozempic,” he says. “It’s not clear all those consequences would be good.”

For instance, an economic principle known as moral hazard predicts that people tend to behave in risky or unhealthy ways if they face no consequence. It’s not yet clear whether people taking GLP-1 agonists adopt healthier lifestyles if they no longer have to worry about gaining weight, although some evidence suggests that the drugs reduce cravings for high-fat and high-sugar food. The same goes for exercise: research hasn’t yet shown whether people become more or less physically active if they lose weight with GLP-1 agonists.

Cheaper versions of blockbuster obesity drugs are being created in India and China

Hammond points out that exercise and healthy diets have benefits beyond weight maintenance. Reducing caloric intake alone won’t solve issues such as weak bones or muscles, driven by sedentary lifestyles and micronutrient deficiencies. “I’m a little worried that looking for a pharmaceutical solution will not address some of the bigger systems problems that we really face,” he says.

Vos agrees that modelling the health effects of weight loss with GLP-1 agonists isn’t straightforward. It’s unclear, he says, whether a drug that causes people to suddenly lose weight can be compared with an intervention that prevents them from gaining it in the first place. The duration of obesity might affect factors such as arthritis and cardiovascular risk, much as a person’s risk of lung cancer increases with the number of years that they smoked.

Michele Cecchini, a physician and economist at the Organisation for Economic Co-operation and Development (OECD) in Paris, says that there are other unknowns as well. For instance, many people regain weight years after undergoing bariatric surgery. That might turn out to also be the case for people who take weight-loss drugs for decades. “These are things that have a potentially huge impact at the population level,” he says.

Cecchini says that the OECD plans to release a report on GLP-1s’ economic impacts next year. His group has previously looked at the effects of obesity on factors such as education, workforce participation and health-care spending. Even climate change is affected when obesity rates rise. Carbon dioxide levels from food manufacturing rise to meet increased demand — particularly with red-meat production — and vehicles have greater emissions owing to heavier loads4.

The challenge with weight-loss drugs, Cecchini says, is the lack of long-term data. There’s a particular lack of independent studies, because many are funded by the drugs’ manufacturers, he adds.

Disparate outcomes

Some data are more solid than others. Researchers could probably confidently project the drug’s impact in people in their sixties and seventies with high body mass indexes (BMIs), says Zachary Ward, a decision-science researcher at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. The effects of obesity on conditions such as diabetes, Alzheimer’s disease and certain cancers that affect this age group are well known.

A study of more than 17,000 people that was published last November5 estimated that Wegovy reduced the risk of heart attacks and strokes by 20% in people who had cardiovascular disease and were also overweight. And another research team estimated that 93 million people in the United States could benefit from Wegovy. If these people all took Wegovy, the team calculated, it would prevent 1.5 million cardiac events over ten years6.

But young people taking GLP-1 agonists are unlikely to encounter these diseases for many years, and factors such as lifestyles and environmental exposures can change over decades. “The longer you go, the more assumptions you make,” Ward says.

Some models show that younger people might benefit most from GLP-1 agonists — if they take them for the rest of their lives. Sexton Ward’s group found that, contrary to conventional wisdom, the drugs are less cost-effective for people with very high BMIs7. Rather, they can prevent more diseases in young people with BMIs between 30 and 40 — the lower end of the range for obesity. “That’s the range where it’s effective enough that 20% weight reduction will reduce the risk of comorbidities,” she says.

Obesity drugs aren’t always forever. What happens when you quit?

Their analysis found that, if everyone in the United States had free access to semaglutide, the resulting drop in obesity-associated diseases would save taxpayers $24.5 billion per year, although this would not include the cost of the drugs themselves.

Sexton Ward agrees that predicting population-level health and economic impacts is difficult owing to scarce data. But she highlights one idea: in a report funded by semaglutide-maker Novo Nordisk that she co-authored, her team found that the GLP-1s could produce much greater economic benefits for Black and Hispanic people in the United States than for white populations8.

US Black and Hispanic populations are, on average, more prone to obesity and related conditions than white populations are — largely because of societal inequalities such as lower average incomes and concomitant difficulties in accessing healthy food. Obesity, in turn, exacerbates other health disparities caused by environmental exposures and discrimination in health care.

“Over time, access to these drugs could begin to shrink some of these disparities,” Sexton Ward says. Although obesity isn’t the only cause of health inequality, she says, “I think it could be a step in the right direction.”

The price issue

Right now, however, the drugs are so expensive that only relatively wealthy people can afford them (although in some US states, there is government health-care coverage under a programme for low-income individuals). If influencers and celebrities can easily lose weight, Rasmussen says, the stigma against obesity might increase. That could further harm people on low incomes, who are most likely to face the social, economic and health consequences of obesity. “That gap will increase as long as it remains expensive,” he says.

The high cost is a particular problem for low- and middle-income countries, where obesity rates are growing twice as fast as in high-income nations, says Adeyemi Okunogbe, a health-policy researcher at the non-profit RAND Corporation in Santa Monica, California. Of the estimated 5 million deaths each year caused by obesity-associated conditions, 77% occur in low- and middle-income countries.

Okunogbe says that obesity-related health-care costs put a double burden of disease on these countries, many of which are already fighting higher rates of infectious diseases. Other costs, such as lost wages owing to higher rates of illness and disabilities, are also magnified in lower-income nations. And in countries without national health systems, individuals would need to pay for GLP-1 agonists out of their own pocket. “It’s a long way off to consider this medicine in this context,” Okunogbe says.

Even countries with public health-care systems are struggling to work out how to pay for the drugs. The UK National Health Service currently funds semaglutide for individual weight loss for only two years, even though the drug must be taken for life to sustain its effect. And US law doesn’t require taxpayer-funded insurance programmes to cover weight-loss treatments (although the same drugs can be covered to treat diabetes). The drugs aren’t even close to affordable: an analysis last year9 by Hur’s group found that the cost of semaglutide would need to drop by 85% to make it cost-effective for adolescents. “The way things stand, there’s not going to be much impact on global health outcomes,” Ward says.

Cecchini says that the OECD’s analysis will consider the impact of cheaper generic and compounded GLP-1 agonist drugs, which are beginning to appear on the market in many countries. And some lawmakers, including in the United States, are beginning to push back on the high costs, particularly after an analysis found that Novo Nordisk could sell Ozempic for $5 per month and still make a profit10.

Until more people can afford the drugs, economists and public-health researchers hoping to look at global impacts are stuck with virtual models instead of studies of actual behaviour. “These drugs hold so much promise, but [the world] has to have access to realize it,” Sexton Ward says.

Credit: nature.com

Team Metabolic Health

Tirzepatide demonstrated long-term weight-loss benefits and prevention of diabetes progression in patients with obesity and prediabetes, but only so long as they continued the weight-loss medication, a speaker reported.

The SURMOUNT-1 trial was a randomized, double-blind, placebo-controlled study for which patients with overweight plus one weight-related comorbidity or obesity and without diabetes were randomly assigned to 72 weeks of tirzepatide 5 mg, 10 mg or 15 mg doses (Mounjaro/Zepbound, Eli Lilly) or placebo.

Long-term tirzepatide reduced body weight and diabetes progression and was well tolerated in people with obesity and prediabetes. Image: Adobe Stock

As Healio previously reported, adults with overweight or obesity without diabetes experienced an approximately 20.9% weight loss at 72 weeks with 15 mg tirzepatide.

The top-line results from the SURMOUNT-1 3-year study were previously reported in August 2024.

At ObesityWeek, Leigh Perreault, MD, associate clinical professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado Hospital, moderated a session overviewing the full 3-year efficacy and safety results of the SURMOUNT-1 trial.

The objective of the SURMOUNT-1 3-year trial was to evaluate the impact of tirzepatide on change in body weight and glycemia in participants with prediabetes and whether the drug prevented progression to type 2 diabetes.

“Here in the U.S., according to the CDC, approximately 40 million Americans live with diabetes,” Perreault said during a presentation. “The epidemic in diabetes, whether here in the U.S. or abroad, is clearly being driven in large part by prediabetes.”

Louis J. Aronne, MD, FACP, FTOS, DANOM, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medical College, discussed the baseline characteristics of the 1,032 SURMOUNT-1 3-year participants, all of whom were diagnosed with prediabetes upon trial enrollment (mean age, 48 years; 64% women; 73.4% white).

Aronne said all participants also had obesity or overweight with one additional weight-related comorbidity. Diagnosis of prediabetes was defined by the American Diabetes Associations cutoffs and required at least two abnormal tests, according to the presentation.

The trial consisted of a 20-week dose-escalation period. Participants with prediabetes who remained on tirzepatide during the first 72 weeks underwent a further 104-week treatment period on tirzepatide 5 mg, 10 mg or 15 mg for a total treatment period of 176 weeks, after which participants were followed up 17 more weeks off-treatment to assess safety for the totality of trial duration, according to the presentation.

Three-year efficacy of tirzepatide for weight loss

Ania M. Jastreboff, MD, PhD, associate professor of medicine and pediatrics at Yale School of Medicine, director of the Yale Obesity Research Center and co-director of the Yale Center for Weight Management, presented the main efficacy data on tirzepatide for weight loss at 3 years.

Key endpoints included mean percentage change in body weight from randomization to week 176 and time to type 2 diabetes onset at week 176 — during treatment period — and week 193 — during post treatment follow-up.

Among the original SURMOUNT-1 cohort of 2,539 participants, 40.6% had prediabetes at randomization and were eligible to continue into the SURMOUNT-1 3-year trial.

Jastreboff reported that the average 3-year weight reduction with tirzepatide 15 mg was approximately 22.9%, translating to an average weight reduction of 34.6 lb to 54.2 lb, depending on the dose of tirzepatide (based on a baseline weight of 236.8 lb).

During 3 years of follow-up, 12.6% of participants assigned to placebo developed type 2 diabetes compared with 1.2% of participants assigned to tirzepatide, which correlated to an HR for diabetes of 0.06 (P < .001), or a 94% reduction in risk for developing diabetes among patients with prediabetes taking tirzepatide. The reported number of SURMOUNT-1 participants needed to treat to prevent one new case of diabetes was nine, according to the presentation.

During the on-drug treatment period, up to 94.5% of participants assigned to tirzepatide had reversion to normoglycemia compared with 60.4% of those assigned to placebo and lifestyle intervention.

Jastreboff and colleagues estimated that approximately 55.2% of diabetes risk reduction was mediated by the weight-loss effects of tirzepatide.

In addition, participants assigned to tirzepatide 15 mg long term also experienced:

1. an average decrease in HbA1c of 0.5% to 0.65%;
2. a mean reduction in baseline waist circumference from 45.9 inches to 38 inches;
3. an average 8 mm Hg decrease in systolic BP and a 5.9 mm Hg decrease in diastolic BP;
4. a more than 14% increase in HDL;
5. a more than 32% decrease in triglycerides;
6. improvement in all lipid levels; and
7. improvement in all eight domains of the Short Form-36v2 quality of life questionnaire.

Upon treatment discontinuation after 176 weeks on tirzepatide, the researchers reported reversals toward baseline in weight, type 2 diabetes risk and blood pressure during the ensuing 17-week off-drug period.

“Treatment with all three doses of tirzepatide demonstrated statistically significant and sustained body weight reduction compared with placebo over more than 3 years,” Jastreboff said during the presentation. “Diabetes prevention with tirzepatide over 3 years resulted in a 94% reduction in progression to diabetes … and nearly 95% reverted from prediabetes to normoglycemia. There was improvement in all cardiometabolic measures. Improvements in all domains of health-related quality of life. Off-drug weight regain was observed and was accompanied by worsening glycemia and increase in progression to type 2 diabetes.”

Three-year safety of tirzepatide for weight loss

Sean Wharton, MD, FRCPC, PharmD, medical director of the Wharton Medical Clinic, adjunct professor at McMaster University in Hamilton, Ontario, and York University in Toronto, academic staff at Women’s College Hospital and clinical staff at Hamilton Health Sciences, presented the main safety results of the 3-year trial.

Wharton reported no significant difference between placebo and any of the tirzepatide doses in mortality rate; however, early discontinuation due to treatment-emergent adverse events was higher among those assigned to tirzepatide compared with placebo.

The most common adverse events reported were gastrointestinal (GI)-related, and those reported were of generally mild to moderate severity. The most common GI-related events included were diarrhea, nausea, constipation and vomiting.

Cholelithiasis was also more frequently observed in the tirzepatide group compared with placebo, a finding consistent with prior studies.

These results were consistent with previously published safety and tolerability of tirzepatide at 72 weeks in SURMOUNT-I and other clinical studies of tirzepatide, according to the presentation.

“The tolerability and safety profile of tirzepatide in this study of 3 years and 9 months duration was generally consistent with incretin-based therapies in people with obesity. The most common adverse events were GI symptoms, generally mind to moderate in severity, occurring primarily during dose escalation. Among adverse events, the most common reasons for discontinuation of the medication were GI adverse events. Gallbladder disease events were reported more frequently in participants from the tirzepatide 10 mg and 15 mg groups compared to the placebo. The finding was mainly due to the increased incidence of cholelithiasis.”

‘Shift focus from weight loss to health gain’

After the presentation of the SURMOUNT-1 3-year safety results, Carel Le Roux, MBChB, MSC, FRCP, FRCPath, PhD, director of the metabolic medicine group at the University College Dublin, summarized the trial as a way to “shift focus from weight loss to health gain.”

“In people with obesity with prediabetes treatment of the disease of obesity, treatment could achieve control of the disease, but not cure. Metabolic complications of obesity got better and stayed better. Functional complications of obesity got better and stayed better. Mental complications of obesity got better but may return close to baseline. Uncertainty remains regarding what happened with appetitive behavior,” Le Roux said. “We can now shift the focus away from weight loss to health gain. When treating patients with prediabetes and obesity we can realize substantial health and functional goals.”

Credit: healio.com

Team Metabolic Health

Danish biotechnology company Zealand Pharma (ZELA.CO), said on Thursday it expected to initiate a so-called Phase 2b trial with its obesity treatment candidate petrelintide in the fourth quarter of 2024.

“We look forward to initiating a large, comprehensive Phase 2b trial very soon and are now exploring collaboration opportunities with potential partners,” Zealand Pharma CEO Adam Steensberg said in a statement.

The company said it expected to initiate the trial with petrelintide in people with overweight or obesity without type 2 diabetes in the fourth quarter and to complete enrolment of patients in the first half of 2025.

It also said it also expected to initiate a Phase 2b trial in the first half of 2025 for patients with overweight or obesity and type 2 diabetes.

Credit: Reuters

Team Metabolic Health

A box of Mounjaro, a tirzepatide injection drug used for treating type 2 diabetes made by Lilly is seen at Rock Canyon Pharmacy in Provo, Utah, U.S. March 29, 2023. REUTERS/George Frey/File Photo

Eli Lilly (LLY.N), opens new tab expects to start selling its weight-loss drug in Hong Kong as early as the end of this year, Bloomberg News reported.

The drugmaker has received approval from the Hong Kong government to sell its tirzepatide injections — branded as Mounjaro — in a device called Kwikpen for both long-term weight management and type 2 diabetes, Eli Lilly told Bloomberg in a statement.

Tirzepatide is the active ingredient in the U.S. firm’s diabetes drug Mounjaro, and weight-loss drug Zepbound.

Eli Lilly did not immediately respond to a Reuters request for comment.

The company had received approval from Chinese regulators for its weight-loss drug tirzepatide in July, further intensifying competition with Danish rival Novo Nordisk (NOVOb.CO), opens new tab in the key Asian market.

Novo Nordisk and Eli Lilly are racing to increase production in a weight-loss market estimated to reach at least $100 billion globally by the end of the decade.

Both companies’ obesity treatments belong to a class of drugs originally developed for diabetes known as GLP-1 agonists.

Credit: Reuters