Three-pronged approach helps preserve muscle mass during weight loss with GLP-1 medications, study finds
New findings to be presented at the European Congress on Obesity (ECO 2025) offer encouraging news for individuals living with overweight or obesity who are prescribed GLP-1 or dual GLP-1/GIP receptor agonists as part of their weight management plan. The six-month study involving 200 adults indicates that with the right support—specifically medical supervision, resistance training, and adequate protein intake—substantial fat loss can be achieved with only minimal reductions in lean muscle mass.
The research, conducted by a team of obesity specialists based in New York, reinforces a growing body of evidence supporting the efficacy of GLP-1-based therapies for treating obesity and highlights key strategies for protecting muscle mass during weight loss.
Understanding GLP-1 Receptor Agonists
GLP-1 (glucagon-like peptide-1) receptor agonists—such as semaglutide and liraglutide—were initially developed to treat type 2 diabetes but have also demonstrated significant benefits in supporting weight loss and managing obesity.
GLP-1 is a type of incretin hormone, produced in the gut, that helps regulate blood glucose levels. Medications in this class work by mimicking or enhancing the effects of the body’s own GLP-1, thereby:
- Stimulating insulin secretion in response to food,
- Inhibiting glucagon release (a hormone that raises blood sugar),
- Slowing gastric emptying,
- Suppressing appetite by promoting satiety.
More recently, medications such as tirzepatide, which activate both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors, have received approval for the treatment of type 2 diabetes and/or obesity. These dual agonists may offer even greater benefits by acting on multiple hormonal pathways involved in appetite and metabolism.
Why Body Composition Matters in Weight Management
While many treatments focus on reducing total body weight, experts stress the importance of maintaining lean muscle mass during weight loss. Muscle plays a vital role in metabolism, mobility, and long-term health. Excessive muscle loss during weight reduction can result in weakness, reduced physical function, and negative metabolic consequences.
To address this, the New York-based research team conducted a six-month prospective cohort study designed to monitor body composition changes in individuals prescribed GLP-1 or dual GLP-1/GIP receptor agonists.
Study Design and Methods
The study enrolled 200 adults aged 18 to 65 years, all of whom had a BMI of 25 kg/m² or higher—placing them in the overweight or obesity category. Participants were prescribed either semaglutide (a GLP-1 receptor agonist) or tirzepatide (a dual GLP-1/GIP receptor agonist). Sixty percent (n = 120) received tirzepatide, while the remaining 40% (n = 80) were given semaglutide.
All participants received care from a board-certified obesity medicine physician, who provided structured guidance on medication adherence, resistance training, and dietary protein intake. Body composition was assessed using the InBody 570—a medical-grade device employing multi-frequency bioelectrical impedance analysis (BIA)—at baseline, three months, and six months.
The InBody 570 measures a range of indicators including total body water, fat mass, skeletal muscle mass, visceral fat, and segmental muscle distribution. Researchers also collected data on medication adherence, physical activity, and dietary patterns throughout the study period.
Importantly, all 200 participants (99 men and 101 women) completed the full study duration.
Key Results: Fat Loss Outpaces Muscle Loss
The average participant age was 47 years, with a mean baseline BMI of 31.4 kg/m².
After six months:
- Women reduced their average body weight from 71 kg (156 pounds) to 62 kg (137 pounds)—a 12% decrease. On average, they lost 10.8 kg of fat mass while losing just 0.63 kg (1.4 pounds) of muscle.
- Men decreased their weight from 101 kg (223 pounds) to 88 kg (193 pounds)—a 13% reduction. Fat mass decreased by 12 kg (25 pounds), while muscle loss averaged just 1 kg (2.4 pounds).
Participants reported high adherence to medication protocols—95% at three months and 89% at six months. Qualitative feedback revealed that those who consistently followed resistance training and protein intake recommendations were more successful in retaining muscle mass and strength.
Comparing Semaglutide and Tirzepatide
While analysis is still underway to examine the comparative effects of semaglutide and tirzepatide on fat and muscle loss, early findings suggest both medications are highly effective in supporting body fat reduction in people living with obesity.
The researchers noted that although some muscle loss is expected during weight loss, targeted interventions—especially when supervised by a qualified obesity medicine specialist—can significantly reduce this loss.
Crucially, the combination of medication adherence, adequate dietary protein, and strength-based exercise emerged as a powerful trio for preserving muscle.
Expert Commentary: Insights and Cautions
Dr Dinabel Peralta-Reich and Dr Alexandra Filingeri, co-authors of the study, shared key insights with Medical News Today.
“This study measured body composition—specifically body fat mass (in pounds), muscle mass (in pounds), and total body weight (in pounds)—in patients at baseline, 3 months, and 6 months while taking GLP/GIP weight loss medications,” they explained.
“The results suggest that, with proper supervision, a protein-rich diet, regular resistance training, and guidance from a trained medical provider, patients can decrease fat mass while minimising muscle loss.”
Dr Peralta-Reich further emphasised:
“We found that, under close supervision and regular follow-up from an obesity medicine specialist, patients were able to lose fat mass with only a minimal decline in muscle mass.”
Commenting on the broader implications, Dr Mir Ali, a board-certified general and bariatric surgeon not involved in the study, added:
“This study was helpful to show that some muscle [loss] can occur with significant weight loss.”
“We see this in our surgical weight loss patients as well, and try to emphasise methods to minimise muscle loss.”
He continued:
“When patients are taking these weight loss medications, they should also implement measures to reduce muscle loss. Muscle loss can lead to weakness and other problems.”
“The main things patients can do is ensure adequate protein intake and exercise. Resistance-type exercises are helpful in maintaining and possibly even building muscle.”
Dr Filingeri noted that the research aimed to provide a clearer understanding of how incretin medications influence fat and muscle mass:
“We found that, under close supervision and regular follow-up from an obesity medicine specialist, patients were able to lose fat mass with only a minimal decline in muscle mass.”
However, she stressed the importance of context when interpreting the findings:
“These results cannot be generalised to patients receiving medication via telemedicine without routine body composition analysis, nor can they be generalised to in-person visits without utilising body composition analysis.”
She concluded by highlighting the need for further studies:
“Further research should explore the roles that diet and exercise play in the success of these medications.”
Conclusion: A Pathway to Safer, Healthier Weight Loss
This six-month investigation provides meaningful insights for clinicians and individuals living with obesity who are using GLP-1 or dual GLP-1/GIP receptor agonists as part of their weight loss journey. By incorporating medical supervision, resistance training, and adequate protein intake, it is possible to minimise the loss of lean muscle and support long-term health outcomes.
As the obesity epidemic continues and these medications become more widely used, tailored, evidence-based strategies like those outlined in this study will be essential to ensuring that weight loss is both effective and sustainable.
CCH Insight:
One of the concerns about AOMs is that large amounts of muscle mass may be lost when people shed weight rapidly, so the results of this study are re-assuring, demonstrating that with the right diet and exercise, lean muscle loss can be minimised. The study is also an excellent reminder that these medications should be taken as an adjunct to lifestyle changes, including a healthy diet and physical activity. With appetite being significantly restricted, it is important to eat a nutrient-dense diet to ensure adequate intake of all essential nutrients, including protein.
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Pfizer halts development of promising oral obesity medication following safety concerns
Pfizer has announced the discontinuation of its once-daily oral obesity treatment, danuglipron, ahead of its transition to the most advanced and costly phase of clinical trials. The decision marks a significant shift in the pharmaceutical giant’s approach to tackling obesity, a therapeutic area that has rapidly gained prominence and commercial value.
The company revealed on Tuesday that it would cease development of the once-daily formulation of danuglipron after a participant in a clinical study experienced a potential drug-induced liver injury. The adverse effect resolved once the individual stopped taking the medication.
A Pfizer spokesperson explained that the once-daily pill was undergoing early-stage testing focused on determining the optimal dosage for people living with obesity. The original plan had been to progress into late-stage clinical trials, which typically serve as the final step before regulatory approval is sought.
Although this version of danuglipron will no longer be pursued, a company representative confirmed: “Pfizer still plans to develop other potential obesity treatments in earlier stages of testing.”
Obesity therapeutics have become one of the most dynamic and financially rewarding segments of pharmaceutical development. In 2024, Eli Lilly’s Zepbound, an injectable medication for obesity, generated close to $5 billion in its first full year on the market. Similarly, Novo Nordisk’s Wegovy has seen substantial commercial success. However, both of these leading therapies require injection, a delivery method that can be a barrier for some individuals.
As a result, there is growing industry interest in developing oral alternatives that offer greater convenience and are likely to be more acceptable to people reluctant to self-inject or attend frequent medical appointments. Eli Lilly is expected to release results later this year from clinical trials investigating several oral obesity treatments currently in development.
Despite the success of these medications, accessibility remains a major challenge. Many people face barriers to treatment due to recent supply shortages or inconsistent insurance coverage. Although both Lilly and Novo Nordisk have recently announced price reductions, the monthly cost of these treatments still runs into the hundreds of dollars, making them unaffordable for many individuals without adequate coverage.
Pfizer’s decision to halt development of the once-daily danuglipron follows an earlier move in late 2023, when the company discontinued its twice-daily formulation of the same drug. That version had advanced to mid-stage testing but was abandoned after more than half the participants in a clinical trial discontinued use.
As part of its latest announcement, a Pfizer spokesperson also confirmed that the company will no longer pursue trials of danuglipron in combination with other medications for obesity treatment.
While the company recalibrates its strategy in the obesity space, the market response remained muted. On Monday morning, shares of New York-based Pfizer Inc. rose by 12 cents to $22.03.
Pfizer’s withdrawal from the danuglipron programme underscores the complexity of developing safe and effective oral medications for obesity. The company’s ongoing commitment to researching new treatments may yet yield novel therapeutic options in a field of growing urgency and unmet need.
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Building minds in code: AI-based ‘digital twins’ of mouse brains open new frontiers in neuroscience
Much like a pilot might practise flight manoeuvres in a simulator, researchers may soon be able to conduct complex neuroscience experiments within a hyper-realistic digital model of a mouse brain. In a groundbreaking study, a team led by Stanford Medicine has developed an artificial intelligence (AI) system that acts as a “digital twin” of the mouse brain’s visual cortex – the region responsible for processing visual information.
This innovation brings us closer to a future in which scientists can explore brain function more safely, efficiently, and in far greater detail than ever before. By simulating how the brain reacts to real-world visual stimuli, these digital replicas allow researchers to investigate cognition and perception without invasive procedures.
A Digital Mirror of the Brain
To create the digital twin, the AI model was trained using vast datasets capturing the activity of real neurons in the visual cortex of mice as they watched clips from feature films. The model, informed by these data, was then able to accurately predict how tens of thousands of neurons would respond to entirely new images and videos.
“If you build a model of the brain and it’s very accurate, that means you can do a lot more experiments,” said Professor Andreas Tolias, PhD, from Stanford Medicine’s Department of Ophthalmology and senior author of the study, published in Nature on 9 April. “The ones that are the most promising you can then test in the real brain.”
Eric Wang, PhD, a medical student at Baylor College of Medicine, served as the lead author of the study.
Generalising Beyond the Known
This new model stands apart from earlier AI simulations of the brain, which were limited to predicting responses to stimuli similar to those in their training datasets. In contrast, the new model has demonstrated an ability to extrapolate and respond accurately to a much wider range of novel inputs. It can even infer physical characteristics of individual neurons, such as their anatomical locations and types.
The model belongs to a new class of AI systems known as foundation models — algorithms trained on extensive datasets that can then apply what they’ve learned to novel scenarios. ChatGPT, for example, is a language-based foundation model. In this case, the model applied foundational principles of neuroscience to visual processing.
“In many ways, the seed of intelligence is the ability to generalise robustly,” said Tolias. “The ultimate goal — the holy grail — is to generalise to scenarios outside your training distribution.”
Lights, Camera, Neural Action
Training the digital twin began with an ambitious experiment: recording over 900 minutes of neural activity from eight mice watching high-energy human films such as Mad Max. These action-packed movies were chosen deliberately. Mice have low-resolution vision — similar to the human peripheral visual field — and are primarily sensitive to movement rather than detail or colour.
“It’s very hard to sample a realistic movie for mice, because nobody makes Hollywood movies for mice,” Tolias quipped. “Mice like movement, which strongly activates their visual system, so we showed them movies that have a lot of action.”
As the mice watched, high-resolution recordings tracked the responses of their visual cortex, while cameras simultaneously monitored their eye movements and behaviours. This data was then used to build a foundational model, which, with a small amount of additional data, could be tailored to create a unique digital twin for any individual mouse.
Simulating the Brain in Silico
Once built, these digital brains responded to fresh images and videos with a high degree of accuracy, closely mirroring the behaviour of their real-world counterparts. This level of precision, according to Tolias, was due to the model being “trained on such large datasets.”
What is particularly remarkable is that the model, trained solely on functional data (neural activity), was also able to generalise to structural data. For one mouse, the AI model accurately predicted the anatomical locations, cell types, and synaptic connections between thousands of neurons in its visual cortex.
To validate these predictions, researchers compared the digital model against high-resolution electron microscopy images from the same mouse’s brain. These data were part of the MICrONS project — an ambitious effort to map the structure and function of the mouse visual cortex in unparalleled detail. The MICrONS findings were published simultaneously in Nature.
An Infinite Laboratory
The implications of this technology are profound. Because a digital twin can outlive the biological organism it models, researchers could theoretically run millions of experiments on a single virtual mouse. This approach could drastically reduce the time, cost, and ethical concerns associated with traditional animal research.
“We’re trying to open the black box, so to speak, to understand the brain at the level of individual neurons or populations of neurons and how they work together to encode information,” Tolias explained.
Already, these AI models are providing new insights. In another related study published simultaneously in Nature, researchers used a digital twin to uncover the mechanisms by which neurons in the visual cortex form connections. While it was previously known that neurons with similar properties tend to form connections, the digital model revealed a more nuanced rule.
The digital twin showed that neurons preferentially connect with others that respond to the same visual stimulus — such as the colour blue — over those located in the same spatial region of the visual field.
“It’s like someone selecting friends based on what they like and not where they are,” Tolias said. “We learned this more precise rule of how the brain is organised.”
What Comes Next?
Looking ahead, the team plans to expand this modelling approach to other areas of the brain and to other species, including non-human primates with more complex cognitive functions.
“Eventually, I believe it will be possible to build digital twins of at least parts of the human brain,” said Tolias. “This is just the tip of the iceberg.”
The project represents a collaborative effort involving researchers from Stanford Medicine, the University of Göttingen, and the Allen Institute for Brain Science.
Funding was provided by multiple institutions, including the Intelligence Advanced Research Projects Activity (IARPA), the National Science Foundation (NeuroNex grant), the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke (grant U19MH114830), the National Eye Institute (grant R01 EY026927 and Core Grant for Vision Research T32-EY-002520-37), the European Research Council, and the Deutsche Forschungsgemeinschaft.
As digital replicas of brains become more advanced, researchers hope that this technology will not only shed light on the mysteries of perception and learning but also pave the way for new therapeutic approaches to brain-related conditions — all while reducing reliance on live animal testing.
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Expanded access to anti-obesity medications could extend life and save society billions
A new white paper from the USC Schaeffer Center has found that broadening access to anti-obesity medications could significantly increase life expectancy and extend disease-free years for people living with obesity, all while delivering a substantial return on investment to society—even after accounting for treatment costs.
More than four in ten adults in the United States are living with obesity, a chronic health condition linked to over 200 diseases including cardiovascular disease, type 2 diabetes, cancer, and dementia. The financial toll of treating these associated conditions is immense, with annual societal costs reaching $260 billion. Despite the arrival of highly effective anti-obesity medications, fewer than one-third of health insurance plans cover them, largely due to concerns over initial expenditure.
According to the Schaeffer Center researchers, expanding access to these medications for all adults without diabetes who meet clinical eligibility criteria could generate as much as $10 trillion in social value. This value stems from improved longevity and health outcomes. Moreover, the societal return on this investment could exceed 13% annually—a figure on par with returns seen from high-impact policies such as early childhood education for disadvantaged populations, and nearly double the average return of the U.S. stock market over the 21st century.
“While the costs of anti-obesity medications have grabbed headlines, our analysis shows why it’s important to consider the lifetime value of treatment. Expanding access will prevent or delay obesity-related comorbidities, resulting in improved quality and quantity of life for many Americans,”
said Alison Sexton Ward, research scientist at the Schaeffer Center and co-author of the study.
The findings come at a pivotal time, as federal policymakers deliberate whether to expand Medicare and Medicaid coverage for anti-obesity medications—a decision that could also set the precedent for broader uptake among private insurers. The latest white paper builds upon a widely cited 2023 report from the Schaeffer Center, which projected that Medicare coverage alone could save the programme as much as $175 billion over the next decade through reduced demand for medical services.
Benefits Go Beyond the Sickest Individuals
To arrive at these conclusions, researchers employed the Future Adult Model, an economic-demographic microsimulation tool, to simulate the lifelong health trajectories, healthcare costs, and other economic outcomes for adults aged 25 and older who qualify for anti-obesity medication under current clinical guidelines, excluding those already diagnosed with diabetes. The analysis examined subgroups across age bands, body mass index (BMI) categories, and varying levels of diabetes risk.
Even though pharmaceutical competition often drives down net prices of high-cost drugs ahead of generic availability, researchers took a conservative stance, assuming stable net pricing until generic entrants are expected in 2032. The estimated net price, reflecting rebates and negotiated discounts, is approximately 55–65% below the list price, aligning with figures used by the U.S. Congressional Budget Office.
The study found that younger, healthier adults stand to gain the most from early treatment. For instance, people aged 25 to 34 who begin taking anti-obesity medications could gain up to 1.8 additional years of life and experience as many as 5.9 more years free from type 2 diabetes.
The researchers calculated the “social value” of expanded access by comparing the monetary worth of prolonged, healthier lives and lower healthcare costs to the price of medication.
Because early treatment yields more years of healthy life, its value is particularly high in younger age groups. For example, initiating treatment in a 25-year-old with low immediate diabetes risk could deliver nearly 30% more lifetime social value compared to beginning treatment in a 35-year-old with similar risk.
“Insurers often limit coverage of anti-obesity medications to sicker patients, such as those with prediabetes or diabetes, but our analysis shows they are likely missing out on a chance to prevent worse and more costly outcomes through early treatment,”
said co-author Darius Lakdawalla, chief scientific officer at the Schaeffer Center and professor at the USC Mann School of Pharmacy and Pharmaceutical Sciences and the USC Price School of Public Policy.
Importantly, the net lifetime social value of treatment was found to be positive for almost every group assessed in the study, not just the youngest or healthiest.
High Return on Investment Across Populations
The study also evaluated the long-term return on investment to society for each dollar spent on expanding access to anti-obesity medications, focusing on the internal rate of return (IRR). This metric reflects the projected annual benefit relative to the cost.
The IRR exceeded 13% across all subgroups with a BMI of 30 or higher, sustained over a 30-year horizon. This suggests that, across the board, investment in broader access to anti-obesity medication could deliver robust and consistent returns for society.
“Expanding access to anti-obesity medication is probably the single most effective policy to improve Americans’ public health,”
said Dana Goldman, co-director of the Schaeffer Center and founding director of the USC Schaeffer Institute for Public Policy & Government Service.
“The challenge will be to do it in a way that rewards innovators but keeps the public costs low.”
The report underscores that, despite the headline-grabbing costs of anti-obesity medications, their long-term benefits—in both health and economic terms—are substantial. As policymakers debate the future of healthcare coverage, the findings offer compelling evidence for the early and equitable use of these medications as a powerful tool in tackling one of today’s most widespread and consequential chronic health conditions.
CCH Insight:
This study makes a very strong case for access to anti-obesity medications for everyone who is eligible – there would be considerable financial and societal benefits. However, as long as these medications are delivered by self-injection ‘pens’, there are likely to be supply issues. Oral versions of these medications are under development, and the sooner they are available, the sooner we are likely to see a leap in accessibility and the possibility of the public health benefits suggested by this study. Our next news item about trials of oral AOM orforglipron provides hope that these oral medications may be available fairly soon.
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Early use of anti-obesity medication more than doubles weight loss
Incorporating an anti-obesity medication just one month after beginning behavioural therapy—rather than the current guideline of waiting six months—can more than double weight loss for individuals who initially struggle with lifestyle changes alone. This is the key finding of a new study from researchers at the Perelman School of Medicine at the University of Pennsylvania, published in Nature Medicine.
Obesity and Its Health Implications
Obesity affects over 40 percent of adults in the United States and is associated with a heightened risk of heart disease, stroke, type 2 diabetes, and certain cancers. Behavioural therapy—also referred to as lifestyle intervention—along with anti-obesity medication, are recognised as effective strategies to support individuals in achieving their weight and health-related goals. However, the effectiveness of these approaches can vary widely among individuals. This study addresses a significant gap in obesity management by demonstrating that those who struggle with one form of treatment may benefit substantially from the timely addition of another.
Most obesity management guidelines recommend an initial six-month period of lifestyle intervention before considering medication. These lifestyle modifications typically involve reducing calorie intake, increasing physical activity, and employing behavioural strategies such as tracking food consumption and exercise. These interventions are often delivered through structured counselling sessions, where trained professionals help participants set realistic goals and provide accountability. However, research indicates that up to 50 percent of individuals undertaking lifestyle interventions alone do not achieve a clinically meaningful weight loss of at least five percent of their starting weight.
Dr Jena Shaw Tronieri, Senior Research Investigator at the Center for Weight and Eating Disorders in the Department of Psychiatry at the University of Pennsylvania, noted the critical lack of research into next steps for individuals who do not respond adequately to behavioural therapy alone:
“Surprisingly little is known about how to help patients who struggle to lose weight when they are already receiving frequent lifestyle counselling sessions. Some experts have suggested that adding an anti-obesity medication should be the next step, but no studies have tested whether this approach actually improves weight loss.”
Early Intervention Leads to Greater Weight Loss
The research team, led by Tronieri, assessed an early intervention approach by identifying individuals who had lost less than two percent of their initial body weight after four weeks of weekly behavioural sessions (equating to less than one pound per week for most participants). These individuals were then randomly assigned to receive either the anti-obesity medication phentermine hydrochloride (15.0 mg per day) or a placebo while continuing with 24 additional weeks of behavioural intervention.
Phentermine, an appetite suppressant, is the longest-approved weight-loss medication currently available, having received U.S. Food and Drug Administration (FDA) approval in 1959.
The results demonstrated a significant disparity in weight loss outcomes:
- Participants who received only the placebo alongside behavioural counselling lost an average of 2.8 percent of their initial weight over the 24-week period.
- In contrast, those who received phentermine experienced a weight loss of 5.9 percent—more than double the amount lost by the placebo group.
For context, an individual weighing 250 pounds (approximately 113 kg) at the study’s outset would have lost around 15 pounds (6.8 kg) with the medication, compared to roughly 7 pounds (3.2 kg) with behavioural therapy alone.
Meanwhile, individuals who were “early strong responders”—those who had already achieved notable weight loss in the first month—continued with lifestyle interventions alone and achieved an additional 5.1 percent reduction in their initial weight over the same six-month period.
Implications for Obesity Treatment
Dr Tronieri emphasised the importance of adapting obesity treatment strategies to prevent disengagement and improve patient outcomes:
“Our results strongly support the addition of anti-obesity medications for patients who do not achieve meaningful weight loss with behavioural methods alone. They also suggest that the medication can be introduced early in treatment, rather than waiting until a patient completes a full six-month programme. Early intervention is crucial because patients who don’t see initial results are more likely to become discouraged and discontinue treatment altogether.”
The study’s findings offer a potential framework for healthcare professionals supporting individuals who find it challenging to lose weight through lifestyle changes alone. While this study focused on phentermine, researchers caution that additional trials are necessary to determine whether newer FDA-approved medications, such as semaglutide or tirzepatide, could yield even greater improvements.
Study co-author Dr Thomas A. Wadden, Professor of Psychology in Psychiatry, noted:
“If the people who were early non-responders took one of the newer approved medications, like semaglutide or tirzepatide, it’s likely they could easily double or triple their weight loss compared to phentermine. Additional research is needed to confirm this hypothesis.”
Future Research Directions
The study was funded by the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116935). Researchers aim to build upon these findings by exploring the effectiveness of alternative medications and refining treatment protocols to maximise weight loss outcomes for those who do not respond to behavioural interventions alone.
This study represents a significant step towards more personalised obesity management, with early introduction of medication offering a promising approach for individuals who find it difficult to achieve weight loss through lifestyle modifications alone.
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GLP-1 agonists improve kidney transplant outcomes in people with type 2 diabetes
A recent study has demonstrated that people with type 2 diabetes who have received kidney transplants experience significantly improved survival rates and a lower likelihood of organ failure when prescribed glucagon-like peptide-1 (GLP-1) receptor agonists, a class of medications originally developed to manage diabetes and now widely used for weight management.
Obesity is a well-documented risk factor for type 2 diabetes and is associated with an increased risk of postoperative complications, including inflammation, organ rejection, and premature mortality. Previous research had indicated that people who had undergone kidney transplantation and subsequently took GLP-1 agonists exhibited a slower decline in kidney function compared to those who had not received the medications. However, there had been uncertainty regarding their routine use in this population due to concerns about potential adverse effects, including pancreatic inflammation, liver complications, and a theoretical increased risk of a rare form of thyroid cancer, particularly in individuals taking immunosuppressive medications to prevent transplant rejection.
Significant Reduction in Organ Failure and Mortality
The new study, conducted by researchers at NYU Langone Health and published in The Lancet Diabetes & Endocrinology, aimed to clarify the benefits and risks of these medications in kidney transplant recipients. The findings revealed that people prescribed GLP-1 agonists—most of whom began treatment within three years of transplantation—were 49% less likely to experience transplant failure, defined as the cessation of kidney function necessitating a return to dialysis, compared to those not taking the medication. Additionally, those prescribed GLP-1s had a 31% lower risk of mortality within five years of starting the treatment.
Dr Babak J. Orandi, MD, PhD, lead investigator of the study, transplant surgeon, and obesity medicine specialist, emphasised the significance of these findings:
“Our study results are the strongest evidence to date that GLP-1 agonist drugs are largely safe and effective tools for addressing type 2 diabetes in kidney transplant recipients.”
Dr Orandi, an associate professor in the Departments of Surgery and Medicine at NYU Grossman School of Medicine, further noted:
“Our research offers a large amount of real-world clinical data to guide the management of benefits and risks of GLP-1 use in kidney transplant recipients.”
Risk of Diabetic Retinopathy
While the study found no increased risk of pancreatic inflammation, liver complications, or thyroid cancer in those prescribed GLP-1s, it did identify a 49% higher likelihood of developing diabetic retinopathy, a leading cause of blindness. This eye condition occurs when elevated blood sugar levels damage the retina’s blood vessels, particularly in cases where blood glucose control is adjusted too rapidly.
Study senior investigator and epidemiologist Dr Mara McAdams-DeMarco, PhD, an associate professor in the Departments of Surgery and Population Health, highlighted the need for close monitoring:
“Our findings also show that while the benefits of GLP-1 drugs are significant, their use does come with some added risk of diabetic retinopathy, suggesting that physicians need to carefully monitor the eye health of kidney transplant recipients with diabetes who are started on these drugs.”
Dr Orandi further elaborated on this point, stating that individuals with poorly controlled diabetes should be screened for diabetic retinopathy prior to starting GLP-1 therapy. He also recommended a gradual titration of the medication dosage in people with severe diabetes or pre-existing eye conditions.
Study Overview and Future Research
The study analysed medical records from the U.S. Renal Data System, which integrates data from the Organ Procurement and Transplantation Network, the U.S. Centers for Medicare and Medicaid Services, and Medicare claims related to prescription drug use. Researchers reviewed data from 18,016 kidney transplant recipients with pretransplant diabetes in the United States between 2013 and 2020. Of these, 1,916 individuals were prescribed GLP-1 receptor agonists, including semaglutide, liraglutide, and dulaglutide, marketed under brand names such as Ozempic, Wegovy, Saxenda, Victoza, and Trulicity.
The study also found that those prescribed GLP-1s were more likely to be younger, female, Black, and from lower-income backgrounds than those who were not prescribed the medication. The researchers emphasised the need for further studies to investigate the biological mechanisms by which GLP-1 agonists enhance kidney health post-transplantation.
Type 2 diabetes remains one of the primary causes of end-stage kidney disease, and with a quarter of a million individuals in the United States currently awaiting a kidney transplant, identifying treatments that improve post-transplant outcomes is of critical importance.
Funding and Disclosures
The study was supported by National Institutes of Health grants R01AG077888, K02AG076883, R01DK114074, R01DK120518, K01DK132490, and K24AI144954.
Besides Dr Orandi and Dr McAdams-DeMarco, researchers involved in the study included Yui Chen, MHS; Yiting Li, MPH; Garyn Metoyer, MD; Michael Weintraub, MD; Sunjae Bae, MD, PhD; Nicole Ali, MD; Bonnie Lonzo, MD; Christine Ren-Fielding, MD; Holly Lofton, MD; Akash Gujral, MS; and Dorry L. Segev, MD, PhD. Additionally, Krista Lentine, MD, from Saint Louis University in Missouri, contributed as a co-investigator.
Dr Orandi has served on an advisory board for Boehringer Ingelheim. Dr Lofton has received advisory board fees, research funding, and speaking fees from Novo Nordisk, Eli Lilly, and Currax. Dr McAdams-DeMarco has received speaking fees from Chiesi. Dr Segev has served as a consultant or received speaking fees from AstraZeneca, Behring, CareDx, CSL, Jazz Pharmaceuticals, Mallinckrodt, Novavax, Novartis, Optum Health Education, Sanofi, Thermo-Fisher Scientific, Transmedics, and Veloxis. None of these companies were involved in the current study. The terms of these relationships are being managed in accordance with NYU Langone Health’s policies and procedures.
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GLP-1 drugs may reduce risk of leukaemia and lymphoma in people with type 2 diabetes
A recent study published in JAMA Network Open suggests that individuals with type 2 diabetes (T2D) who are treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a lower risk of developing haematologic cancers, including leukaemia and lymphoma, compared to those using insulin or metformin.
Background
Both obesity and type 2 diabetes are recognised as independent risk factors for various types of cancer, including haematologic malignancies. GLP-1RAs have emerged as a promising therapeutic option due to their benefits in weight management, immune modulation, and glycaemic control. Previous research has linked GLP-1RAs to a lower incidence of solid tumours, yet their relationship with haematologic cancers remains largely unexplored. This study sought to fill this knowledge gap by comparing cancer risks in individuals receiving GLP-1RAs versus those using metformin or insulin.
Study Overview
Researchers conducted a retrospective cohort analysis using the TriNetX database, a large repository containing health records for approximately one-quarter of the United States population. The study included individuals with a T2D diagnosis who were prescribed either GLP-1RAs (such as exenatide, lixisenatide, tirzepatide, liraglutide, albiglutide, semaglutide, or dulaglutide), insulin, or metformin between 30 April 2005 and 31 October 2023.
To ensure robust comparisons, individuals with a prior diagnosis of haematologic cancer or those who had been prescribed antidiabetic medication before their T2D diagnosis were excluded. The study’s primary objective was to assess the incidence of first-time haematologic cancer diagnoses across different treatment groups. Two separate analyses were conducted: one comparing GLP-1RA users to metformin users and another comparing them to insulin users.
To account for potential confounding factors, the study employed propensity score matching based on multiple variables, including weight status, demographic characteristics, diabetic complications, body mass index (BMI), glycated haemoglobin (HbA1c), cancer screening history, genetic predisposition, exposure to radiation, intensive care unit (ICU) admissions, concomitant antidiabetic therapies, adverse social determinants of health, and exposure to cytotoxic agents. The researchers then utilised Kaplan-Meier survival analysis and Cox proportional hazard models to estimate cumulative cancer incidences and hazard ratios with 95% confidence intervals.
Key Findings
The study identified over 1.6 million individuals with type 2 diabetes. Among them, 51,617 were prescribed GLP-1RAs, 938,602 received insulin, and 611,115 were treated with metformin. The average duration of GLP-1RA prescriptions was 485 days. Following propensity matching, 50,590 participants were included in the GLP-1RA–metformin comparison, and 47,716 were included in the GLP-1RA–insulin comparison.
Comparison with Metformin
GLP-1RA use was associated with a significantly lower risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) when compared to metformin. However, the researchers noted that metformin itself has been linked to cancer-protective effects, which may explain why the overall reduction in haematologic cancer risk associated with GLP-1RAs was limited in this comparison. Ultimately, no statistically significant difference was observed in the combined risk of all haematologic cancers between GLP-1RA and metformin users.
Comparison with Insulin
In contrast, when compared to insulin users, those prescribed GLP-1RAs exhibited a markedly lower risk of developing a range of haematologic cancers. Specifically, GLP-1RA users had a significantly reduced risk of lymphoid leukaemia, myeloid leukaemia, MPN, MDS, amyloidosis, non-Hodgkin lymphoma, monoclonal gammopathy, and multiple myeloma. Overall, GLP-1RA use was linked to a 54% lower risk of developing any haematologic malignancy compared to insulin use.
Implications and Conclusion
The findings suggest that GLP-1RAs may offer protective effects against haematologic cancers, particularly in comparison to insulin. This effect is likely influenced by the immunomodulatory properties of GLP-1RAs and their role in promoting weight loss. Notably, these protective associations appeared to be independent of glycaemic control, potentially due to a reduction in pro-inflammatory cytokines that are involved in the dysregulation of haematopoiesis and the development of conditions such as MPN and MDS.
Despite these promising results, the study has several limitations. Residual confounding factors cannot be entirely ruled out, and the analysis did not explore dose-response relationships or account for potential age-related variations in cancer risk. Additionally, as this was a retrospective study relying on diagnostic codes from electronic health records, inaccuracies in coding and unmeasured confounders could have influenced the results.
The authors emphasised that metformin, a comparator in the study, is already known to have cancer-protective properties, which may explain why the benefits of GLP-1RAs appeared more pronounced when compared to insulin rather than metformin. Given these findings, GLP-1RAs could represent a promising avenue for reducing cancer risk in individuals with type 2 diabetes. However, further research is required to elucidate the underlying biological mechanisms and confirm these observational findings in prospective clinical trials.
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Rising prescriptions for obesity management medications reflect growing public interest
The number of prescriptions for obesity management medications (OMDs) has increased significantly in recent years, with a corresponding rise in online search activity, according to a study published on 29 January in JAMA Network Open.
Dr Philipp Berning, from Johns Hopkins University School of Medicine in Baltimore, and colleagues conducted a repeated cross-sectional study examining prescription patterns and online search trends for OMDs. Their research explored the correlation between the growing use of these medications and public engagement, analysing trends visually and performing quantitative correlation calculations.
The study revealed that a total of 69,213,936 prescriptions for OMDs were dispensed in the United States during the research period. The data showed a steady increase in prescription rates, rising from 0.76 to 0.80 million between July 2017 and June 2018, and from 1.29 to 1.51 million between March 2023 and February 2024. This represents a mean annual growth rate of 5.3 per cent. By February 2024, the total number of OMD prescriptions reached 1.5 million in a single month, accounting for 0.41 per cent of all prescriptions issued during that time.
Among the most commonly prescribed OMDs were phentermine, semaglutide (marketed as Wegovy), liraglutide (Saxenda), and tirzepatide (Zepbound). By February 2024, phentermine had approximately 0.74 million monthly prescriptions, while Wegovy and Zepbound had 0.42 million and 0.25 million monthly prescriptions, respectively.
Online search trends closely mirrored these prescribing patterns. Search volumes for Wegovy, Zepbound, and phentermine in February 2024 were recorded at 636.3, 468.9, and 301.8 searches per 10 million, respectively. The strongest correlation between prescription rates and online search volumes was observed with Wegovy and Zepbound, indicating heightened public interest in these newer treatments.
“These findings may provide insight for health care professionals and policy makers, as they highlight the rapid adoption by clinicians (including nonphysician professions) of state-of-the-art obesity treatments and their growing public interest,” the authors wrote.
One author of the study disclosed financial ties to the biopharmaceutical industry, a factor that should be considered when interpreting the findings.
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Researchers aim to minimise side effects of obesity medications through groundbreaking study
A pioneering £1.2 million research initiative is now underway at University College London (UCL) and the Rowett Institute at the University of Aberdeen, seeking to refine the effectiveness of weight-loss medications while reducing their associated side effects. The study, funded by the Medical Research Council, will investigate the precise mechanisms through which these drugs act in the brain, with the goal of developing improved treatments that minimise discomfort while maximising therapeutic benefits.
The Promise and Challenges of Semaglutide
Semaglutide, an anti-diabetic medication marketed under brand names such as Wegovy and Ozempic, has gained widespread recognition for its ability to support weight management. The drug works by acting on the brain to reduce food intake, helping people with obesity or overweight to achieve significant weight loss.
However, despite its effectiveness, semaglutide can produce unpleasant side effects, including nausea and vomiting. These adverse reactions can make it difficult for individuals to adhere to long-term treatment, ultimately reducing the drug’s overall effectiveness in managing weight.
Investigating the Brain’s Role in Drug Response
Leading the study are Professor Lora Heisler of the Rowett Institute and Professor Stefan Trapp of UCL Biosciences, who will spend the next three years mapping out how semaglutide interacts with the brain. Their research will focus on identifying specific neural pathways that influence different aspects of eating behaviour, such as reducing meal size, encouraging healthier food choices, slowing digestion, and diminishing the brain’s reward response to highly palatable foods.
Crucially, the study will also examine the pathways responsible for triggering nausea and other unwanted side effects. By distinguishing between these different mechanisms, the researchers aim to uncover ways to modify how the drug acts in the brain, potentially paving the way for future medications that retain semaglutide’s benefits without the drawbacks.
Aiming for More Effective and Tolerable Treatments
Professor Trapp highlighted the importance of this research in advancing obesity treatment, “While semaglutide and similar drugs have been very effective in helping people with diabetes and show much promise in helping people to lose weight, we still do not know that much about how exactly they work in the brain.”
He noted that his laboratory has conducted extensive studies on the glucagon-like peptide-1 receptor (GLP-1R), the brain target of semaglutide. By mapping out the drug’s mechanism in greater detail, Trapp and his team hope to contribute to the development of more refined medications with fewer adverse effects.
Professor Heisler further emphasised the potential impact of their findings, “There is huge interest in how the brain targets of semaglutide and similar drugs could be switched on in a slightly different or more targeted way. Drugs that can do this could work better, have effects that last longer, and produce specific therapeutic obesity treatment benefits without the nausea side effect.”
She also pointed out that such research is only possible due to recent technological advancements, stating, “We can only now do these types of studies because of the latest technological advances, and we expect our results will provide the blueprint to develop even better obesity medications in the future.”
Implications for Future Obesity Treatments
This study could play a crucial role in shaping the next generation of obesity medications, offering new treatment options that are not only effective but also better tolerated. As more people turn to pharmacological treatments for weight management, research like this is essential to ensuring that these interventions remain both accessible and sustainable for long-term use.
By deepening the scientific understanding of how semaglutide works in the brain, researchers at UCL and the Rowett Institute aim to refine and improve the treatment landscape, ultimately providing more effective and tolerable solutions for individuals seeking to manage their weight through medical therapy.
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GLP-1 drugs linked to fewer surgery complications in people with diabetes
Individuals living with diabetes who were prescribed GLP-1 receptor agonist medications, such as tirzepatide and semaglutide, experienced significantly lower rates of hospital readmission, wound reopening, and haematoma following surgery, according to a large-scale study. The research was conducted by experts from Weill Cornell Medicine, Columbia University Vagelos College of Physicians and Surgeons, and NewYork-Presbyterian.
Published on 20 December in the Annals of Surgery, the study analysed anonymised hospital data from 74,425 surgical procedures performed on 21,772 individuals with diabetes over a three-and-a-half-year period, concluding in July 2023.
The findings revealed that individuals prescribed GLP-1 receptor agonists—commonly referred to as GLP-1 drugs—demonstrated a:
- 12% reduction in the likelihood of hospital readmission within 30 days post-surgery,
- 29% decrease in the risk of wound reopening within six months, and
- 56% reduction in the risk of haematoma (a localised collection of blood caused by bleeding) at the surgical site compared to those not on these medications.
“These findings from such a large number of patients and procedures suggest that taking these drugs shouldn’t worsen overall post-surgical complications and may even reduce the likelihood of some of them,” said Dr Jason Spector, senior author of the study, chief of the division of plastic and reconstructive surgery at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, and a professor of surgery at Weill Cornell Medicine.
Background on GLP-1 Medications
GLP-1 receptor agonists were originally developed in the early 1990s to manage diabetes, with the first medications reaching clinical use in 2005. In 2014, regulatory authorities, including the US Food and Drug Administration (FDA), approved their use for treating obesity. These drugs function by activating the GLP-1 receptor on cells within the pancreas and other organs, thereby stimulating insulin release, which subsequently lowers blood sugar levels and suppresses appetite.
The recent widespread adoption of GLP-1 drugs prompted Dr Spector and first author Dr Seth Aschen, then a plastic surgery resident at NewYork-Presbyterian/Weill Cornell Medical Center, to investigate whether individuals with diabetes undergoing surgery face a greater or reduced likelihood of complications while on these medications.
Study Methods and Analysis
The research team analysed anonymised electronic health records from NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian/Columbia University Irving Medical Center. They reviewed all surgical procedures involving individuals with diabetes from February 2020 to July 2023, ensuring at least six months of follow-up data for each case.
The investigators focused on hospital readmission rates within 30 days and four other post-surgical complications over the follow-up period. These included wound reopening, haematoma, bleeding, and infection. To ensure robust comparisons, a “propensity matching” system was employed to pair individuals prescribed GLP-1 drugs with similar individuals not taking these medications. This approach minimised the influence of external factors unrelated to the drugs themselves.
Key Findings
Surprisingly, the results indicated that individuals with diabetes taking GLP-1 medications were slightly less likely to require hospital readmission within 30 days of surgery, suggesting a reduction in overall complications.
Among specific complications studied:
- Bleeding and infection rates were consistent between both groups.
- The risk of wound reopening and haematoma was significantly lower in individuals taking GLP-1 drugs. Specifically, those prescribed these medications had 71.1% of the risk of wound reopening and 44.0% of the risk of haematoma compared with those not on GLP-1 drugs.
Understanding the Underlying Mechanisms
While the exact reasons for these beneficial outcomes remain unclear, diabetes is known to impair wound healing, potentially increasing post-surgical risks. Interestingly, the study found that better blood sugar control was unlikely to explain the positive effects, as individuals on GLP-1 drugs had slightly higher average blood sugar levels than their counterparts.
Other research suggests that GLP-1 medications may enhance wound healing through mechanisms such as reducing clotting, promoting the formation of new blood vessels to nourish tissues, and lowering inflammation. “These mechanisms may help explain the observed benefits,” Dr Spector commented.
Future Directions
Dr Spector and his team are now expanding their research to examine whether GLP-1 drugs influence post-surgical complications in individuals without diabetes.
By shedding light on these potential benefits, this study underscores the importance of further research into GLP-1 medications and their broader implications for improving surgical outcomes.
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Mounjaro gains momentum in the UK’s private obesity treatment market, outpacing Wegovy
In the UK’s private obesity treatment market, Eli Lilly’s Mounjaro is becoming the preferred choice over Novo Nordisk’s Wegovy, according to insights from online pharmacies and patients. The shift suggests that the U.S.-based pharmaceutical company is challenging its European competitor’s early dominance in the sector.
The popularity of Mounjaro stems from its greater efficacy in supporting weight loss, as confirmed by six online pharmacies and two individuals using the drug. Despite some pharmacies charging up to 40% more for Mounjaro’s introductory doses compared to Wegovy, its effectiveness appears to outweigh the higher cost for many users.
“Mounjaro is now vastly outstripping Wegovy,” stated James O’Loan, CEO of Chemist4U. According to O’Loan, over the past three to four months, approximately 70% of his pharmacy’s sales have been attributed to Mounjaro.
Private Market Growth
Chemist4U and Simple Online Pharmacy estimate that as many as 500,000 people in the UK are using either Mounjaro or Wegovy via prescriptions obtained through private online pharmacies. Unlike Wegovy, which is accessible through the National Health Service (NHS) but only in specialist obesity clinics under limited conditions, Mounjaro is currently unavailable through the NHS. However, it is expected to become available next year.
The government revealed last year that NHS services had the capacity to treat around 35,000 patients with Wegovy, but no public data exists on the number of prescriptions issued.
Mounjaro entered the UK market in February 2024, marking one of the first launches outside the U.S. and one of a few countries where it directly competes with Wegovy. Novo Nordisk introduced Wegovy in the UK in September 2023. Government statistics indicate that approximately two-thirds of adults in the UK are living with overweight or obesity, making the country a significant market for obesity treatments.
Rising Demand for Obesity Medications
The global obesity drug market is projected to reach a value of $150 billion annually within the next decade. The UK, as one of Europe’s more populous markets, is witnessing significant growth in demand for obesity treatments.
O’Loan reported that Chemist4U is selling approximately 40,000 pens of Mounjaro and Wegovy combined each month, with each pen representing about one month’s supply. The pharmacies interviewed noted that availability of both medications has stabilised since the summer following an earlier period of shortages.
Online listings indicate that one-month starter doses of Wegovy cost between £109 and £138. Similarly, Mounjaro starter doses are priced at approximately £115.
Novo Nordisk’s leadership in the obesity drug market made it Europe’s largest company by market capitalisation last year. However, increasing competition from Eli Lilly has led to a 16% decline in Novo’s market value since its peak in June. Lilly’s rapid growth has boosted its shares by 37% this year, outperforming Novo’s 12% gain.
Comparative Efficacy
Clinical trial data have played a pivotal role in shaping preferences for Mounjaro. Before regulatory approval, trials demonstrated that individuals using Wegovy achieved an average weight reduction of 15%, while Mounjaro users saw nearly 23% weight loss when combined with a balanced diet and exercise.
Recent study results, published last week, provided the first direct comparison between the two medications under identical trial conditions. These findings reinforced Mounjaro’s superior effectiveness in facilitating weight loss.
Novo Nordisk declined to comment on UK sales but emphasised that prescribing decisions should prioritise individual patient needs. Eli Lilly also declined to comment.
Individual Experiences and Pharmacy Trends
Alan, a 54-year-old financial services professional from London, switched to Mounjaro in March 2024 after using Wegovy since October 2023. Concerned about hitting a weight loss plateau, he opted for Mounjaro despite needing to start at the lowest dose and gradually increase. Within the first month, Alan lost one kilogram—more than he had achieved on the highest dose of Wegovy before switching.
“Efficacy drove my switch,” Alan explained. “It was a no-brainer; it seemed the obvious thing to try.”
Pharmacy data align with such individual accounts. Matt Vickers, clinical director at Juniper Pharmacy, reported that 70% to 80% of their new clients are opting for Mounjaro. Similarly, UK pharmacy chain Superdrug dispensed three times as many prescriptions for Mounjaro as Wegovy in October. Online pharmacy MedExpress noted a growing preference among new customers for Mounjaro.
Another individual, John, who preferred to use his middle name, began his weight loss journey with Novo Nordisk’s diabetes medication Ozempic, which contains the same active ingredient as Wegovy. John lost 18 kilograms using Ozempic and exceeded his goal by shedding an additional 20 kilograms. Despite this success, he plans to transition to Mounjaro in January to further enhance his outcomes.
Future Outlook
The competition between Mounjaro and Wegovy highlights a rapidly evolving landscape in obesity care, with patients prioritising efficacy and accessibility. As demand continues to grow, both manufacturers will likely play a critical role in shaping the future of obesity management in the UK and beyond.
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Anti-obesity medications linked to reduced alcohol consumption in weight loss study
A recent study published in JAMA Network Open has revealed intriguing insights into the behavioural effects of anti-obesity medications (AOMs), particularly their impact on alcohol consumption. Conducted within the WeightWatchers (WW) Clinic telehealth weight management programme, the research examined alcohol use patterns among participants who initiated AOMs, with nearly half reporting a decrease in alcohol consumption.
How Do Anti-Obesity Medications Impact Alcohol Use?
AOMs, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are well-established for promoting significant weight loss. However, emerging evidence highlights their potential benefits beyond weight management. GLP-1 RAs have been associated with reduced incidence and recurrence of alcohol use disorder, hinting at their broader therapeutic scope.
Understanding the mechanisms underpinning these effects is vital. Comparative studies examining how different AOMs influence alcohol use could pave the way for enhanced approaches to weight management and addiction treatment. This research underscores the need for further exploration of the behavioural impacts of these medications.
Study Overview
This study included participants from the WW telehealth weight management programme who had initiated an AOM between January 2022 and August 2023 and refilled their prescription between October and November 2023. Participants using AOMs prior to enrolment or with a history of bariatric surgery were excluded, as these factors may alter alcohol use disorder risk.
The study adhered to rigorous ethical and reporting standards, receiving approval from the Henry Ford Health institutional review board and following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Data were deidentified, negating the need for informed consent.
Participants completed baseline surveys capturing demographic details, including age, sex assigned at birth, race, ethnicity, height, weight, and weekly alcohol consumption. Their body mass index (BMI) was calculated from self-reported height and weight. Follow-up surveys assessed changes in alcohol use at the time of AOM refill. Statistical analyses, including multivariate logistic regression, evaluated alcohol use trends, with R software used for computations.
Findings
The study included 14,053 participants, 86% of whom were women, with an average age of 43.2 years and a mean BMI of 36. Most participants (86%) were prescribed second-generation GLP-1 RAs, such as tirzepatide or semaglutide, while others received first-generation GLP-1 RAs, bupropion/naltrexone, or metformin. Participants represented a spectrum of obesity classes: 41.3% were classified as obesity class I, 26% as class II, and 21% as class III.
At baseline, 53.3% of participants reported alcohol use. Among this group:
- 45.3% reduced alcohol consumption after starting an AOM.
- 52.4% reported no change in their drinking habits.
- 2.3% experienced an increase in alcohol use.
Across all participants, 24.2% experienced a reduction in alcohol use. Individuals with higher obesity classes and greater baseline alcohol consumption were more likely to report reduced alcohol use. Participants prescribed bupropion/naltrexone showed a higher likelihood of reducing alcohol consumption compared to those on metformin. However, after adjusting for weight loss, this association lost statistical significance, suggesting that reductions in alcohol use may be partly mediated by weight loss rather than medication-specific effects.
On average, participants experienced a 12.7% reduction in initial body weight over approximately 224.6 days between AOM initiation and follow-up.
Interpreting the Results
The findings point to several potential mechanisms driving reduced alcohol use. Pharmacologically, naltrexone, a component of some AOMs, is known to suppress alcohol cravings. GLP-1 RAs may also diminish the rewarding effects of alcohol consumption. Additionally, behavioural factors associated with weight management programmes, such as encouragement to limit alcohol for calorie control and cognitive restraint, likely contributed to these outcomes.
Conclusion
This study highlights a notable secondary benefit of AOMs: their potential to support reduced alcohol consumption among individuals managing obesity. Nearly half of participants who consumed alcohol at baseline reported a decrease in their intake after starting AOM therapy. These findings offer promising implications for the dual role of AOMs in addressing obesity and its associated behavioural challenges. Further research is essential to deepen our understanding of these interactions and optimise therapeutic approaches in weight management and addiction care.