Obesity Care Tag

GLP-1 RAs Improve Sleep Apnoea Outcomes in People With Obesity

Key Takeaways: 

• GLP-1 receptor agonists (GLP-1 RAs) reduced the apnoea-hypopnoea index (AHI) by 5.7 to 21.9 events per hour across six meta-analyses, with tirzepatide achieving disease remission in 42% to 50% of adults with moderate to severe obstructive sleep apnoea (OSA) and obesity in the SURMOUNT-OSA trials.
  
• The benefits appear to be driven primarily by weight loss, including reductions in tongue fat and parapharyngeal adipose tissue, although emerging preclinical evidence points to possible weight-independent mechanisms.
  
• Continuous positive airway pressure (CPAP) still delivers greater AHI reductions, and the review authors position GLP-1 RAs as a complementary therapy rather than a replacement, best suited to people with a BMI above 30 who cannot tolerate CPAP and have obesity-related comorbidities.
  
  
  

A new treatment avenue for obesity-related sleep apnoea

GLP-1 RAs significantly improve outcomes for people living with both OSA and obesity, according to the findings of a review published in JAMA Otolaryngology–Head & Neck Surgery.

Obesity is common among people with OSA, yet until recently there were no medicines specifically aimed at treating excess body weight in this population. That changed towards the end of 2024, when the US Food and Drug Administration (FDA) approved tirzepatide for the treatment of moderate to severe OSA in adults with obesity. The approval was based on positive results from the phase 3 SURMOUNT-OSA trials.

In the recent review, researchers examined the effects of several medicines acting on the GLP-1 receptor in OSA, including tirzepatide, semaglutide, liraglutide, exenatide and retatrutide.

What the evidence shows

Data drawn from six previous meta-analyses showed that GLP-1 RA use reduced AHI by between 5.7 and 21.9 events per hour.

The SURMOUNT-OSA trials, which enrolled adults living with moderate to severe OSA and obesity, found that tirzepatide reduced AHI by approximately 20 to 24 events per hour compared with placebo. Participants also achieved an average weight loss of 18% to 20%.

Disease remission was achieved in 42% to 50% of these participants. In the trials, remission was defined as an AHI of fewer than 5 events per hour, or fewer than 15 events per hour in the absence of symptoms.

Weight loss as the main driver

According to the study authors, the benefits of GLP-1 RAs were primarily driven by weight loss. Studies have shown that these medicines reduce both tongue fat and parapharyngeal adipose tissue, each of which contributes to upper airway collapse.

The link between body weight and OSA severity is well established. Findings from the Wisconsin Sleep Cohort Study showed that a 10% increase in body weight was associated with a 32% increase in AHI, while the same degree of weight loss was associated with a 26% reduction in AHI.

Possible weight-independent effects

The authors also highlighted early research suggesting that GLP-1 RAs may influence OSA through mechanisms beyond weight loss.

“Emerging preclinical evidence has suggested potential weight-independent effects through carotid body [GLP-1] receptor modulation of chemosensitivity (affecting loop gain), leptin pathway interactions that are associated with upper airway neuromuscular control, and NLRP3 inflammasome suppression,” the study authors noted.

For healthcare professionals seeking to deepen their understanding of how these therapies work and where they fit within wider obesity care, The College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme course explores this rapidly evolving class of medicines.

How GLP-1 RAs compare with CPAP

While medicines acting on the GLP-1 receptor are effective in treating OSA, their effects are more limited than those of CPAP, the established standard treatment. According to a previous umbrella review comparing OSA interventions, CPAP delivers greater AHI reductions, of approximately 31 events per hour compared with 22 events per hour for tirzepatide.

The review also identified further limitations of GLP-1 RAs, including:

• uncertainty about their impact on cardiovascular outcomes
• weight regain when treatment is stopped
• data suggesting that tirzepatide may not be cost-effective for treating OSA under commonly used thresholds
  
  
  

Positioning GLP-1 RAs in clinical practice

Rather than replacing existing treatments, the authors see GLP-1 RAs as one part of a broader management strategy.

“This review suggests that GLP-1 RAs offer otolaryngologists a disease-modifying adjunct for obesity-related OSA that is best positioned as complementary therapy alongside CPAP, preoperative optimization before upper airway surgery, or potentially to expand hypoglossal nerve stimulator candidacy,” the review authors said.

Who may benefit most

The authors advised that GLP-1 RAs are appropriate options for people with a body mass index (BMI) above 30 who have inadequate tolerance to CPAP and who are living with obesity-related comorbidities.

However, they noted that these medicines are not suitable for people without obesity, or for people whose OSA is primarily caused by anatomical obstruction or who have central sleep apnoea.

Disclosure: One author declared affiliations with biotech, pharmaceutical and/or device companies. Please see the original reference for a full list of the authors’ disclosures.

CCH insight

As GLP-1 RAs extend into new indications such as obstructive sleep apnoea, healthcare professionals need a clear understanding of the evidence, appropriate patient selection and the limitations of these therapies. GLP-1RA Therapy: The Complete Programme from The College of Contemporary Health helps clinicians stay up to date with this fast-moving area of practice.

Explore GLP-1RA Therapy: The Complete Programme →

Source: JAMA Otolaryngology–Head & Neck Surgery

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Diet Drinks Match Water for Long-Term Weight Loss in Landmark Two-Year Trial

Key Takeaways: 

• The SWITCH trial, described by its authors as the longest and most comprehensive randomised controlled trial of non-nutritive sweetened (NNS) soft drinks to date, found that diet drinks performed similarly to water for weight loss and weight maintenance over 104 weeks.
  
• Among 493 adults living with overweight or obesity, weight loss was comparable between groups (4.8 kg in the NNS beverage group vs 3.7 kg in the water group), with no clinically meaningful differences in blood pressure, cholesterol or other metabolic measures.
  
• The findings challenge concerns that sweeteners disrupt appetite or cause long-term metabolic harm and may help inform future World Health Organization (WHO) guidance on non-sugar sweeteners.
  
  
  

A long-term look at diet drinks and weight management

Researchers at the University of Liverpool have completed what they describe as the longest and most comprehensive randomised controlled trial to date examining non-nutritive sweetened (NNS) soft drinks.

Non-nutritive sweeteners are low-calorie or calorie-free sugar substitutes commonly used in foods and beverages. The 104-week study found that NNS beverages, including diet soft drinks, performed similarly to water when it came to long-term weight management.

The peer-reviewed research was led by Professor Jo Harrold, Dean of Psychology at the University of Liverpool, alongside Professor Jason Halford, Professor of Biological Psychology & Health Behaviours at the University of Leeds (formerly of the University of Liverpool). The study was funded by the American Beverage Association. According to the researchers, the study team operated independently from the funder and retained full control over the analysis and reporting of the results.

Diet drinks compared with water over two years

The findings, published in the British Journal of Nutrition, provide long-term clinical evidence on beverages containing three commonly used sweeteners: aspartame, acesulfame potassium (acesulfame-K) and sucralose. Researchers found that these drinks were comparable to water in supporting both weight loss and long-term weight maintenance.

The SWITCH trial included 493 adults living with overweight or obesity who took part in a structured behavioural weight management programme. Participants were randomly assigned to drink either water or commercially available diet beverages each day. The amounts of sweeteners consumed remained well within established European Food Safety Authority (EFSA) safety thresholds.

Overall, the results did not support concerns that NNS beverages interfere with appetite regulation or cause long-term metabolic harm.

Weight loss and metabolic health outcomes

The trial reported several key findings across the two-year period:

• Comparable weight loss: after 104 weeks, weight loss was similar between the NNS beverage group and the water group (−4.8 kg vs −3.7 kg), with the difference not statistically significant.
  
• Sustained results: both groups maintained their weight reductions across the full two-year study, including during the final year, when participants no longer received assistance.
  
• Body measurements and composition: participants in both groups experienced reductions in waist and hip circumference, along with improvements in body composition and several metabolic biomarkers.
  
• No meaningful metabolic differences: researchers found no clinically meaningful differences in measures such as blood pressure and cholesterol linked to long-term consumption of aspartame, acesulfame-K or sucralose compared with water.
  
• Reduced sugar intake: sugar intake fell in both groups, with a slightly larger reduction among participants drinking NNS beverages.
  

For healthcare professionals supporting people with weight management, these findings reinforce the value of practical, evidence-based dietary swaps within a structured programme. Clinicians looking to strengthen their confidence in this area may find The College of Contemporary Health’s Nutrition & Weight Management Essentials CPD course a useful way to build their knowledge of dietary approaches to weight management.

Findings add to the sweetener debate

The results are relevant to recent WHO guidance advising against the use of non-sugar sweeteners for weight control, which was issued because of uncertainty in observational research. The SWITCH trial adds long-term randomised controlled evidence that may help inform future global recommendations.

Professor Joanne Harrold said: “The University of Liverpool is one of the UK’s leading research-intensive higher education institutions, with a key focus on public health. These latest findings show that concerns about sweeteners disrupting appetite or causing weight gain are not supported when tested in a rigorous, long-term randomized trial. We hope this evidence informs future WHO guidance and public health policy.”

How the SWITCH trial was designed

The effectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH) trial was developed to address two related questions: how reducing dietary sugar might affect weight management, and whether replacing sugar with non-nutritive sweeteners changes appetite regulation. The newly published results build on earlier findings reported in the International Journal of Obesity in 2023.

Professor Jason Halford, of the University of Leeds and the University of Liverpool, concluded: “This study provides the long-term clinical evidence that has been missing from international discussions. For people trying to manage their weight, non-nutritive sweetened beverages offer an effective alternative to sugar-sweetened drinks – and perform equivalently to water over two years.”

The paper, ‘Effect of non-nutritive sweetened beverages versus water on body weight: long-term results of a randomised controlled trial’, was published in the British Journal of Nutrition.

CCH insight

Supporting people to make sustainable dietary changes is central to effective weight management. Our Nutrition & Weight Management Essentials CPD course helps healthcare professionals apply current evidence on nutrition and weight management in everyday practice.

Explore Nutrition & Weight Management Essentials → 

Source: British Journal of Nutrition

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Mounjaro May Switch On the Body’s Calorie-Burning Brown Fat, Mouse Study Suggests

Key Takeaways: 

• A study in mice found that tirzepatide (Mounjaro) activates brown adipose tissue, a type of fat that specialises in using energy, and that this effect cannot be explained by reduced food intake alone.
  
• Unlike earlier drug-based attempts to activate brown fat, which were often hampered by side effects affecting the heart, tirzepatide shows cardiovascular benefits.
  
• The researchers stress that the findings come from mice and need to be confirmed in humans, but suggest they could pave the way for more personalised obesity treatment based on a person’s overall metabolic status. 
  
  
  

Looking beyond appetite suppression

Tirzepatide has become an important treatment for obesity and related conditions such as type 2 diabetes, yet scientists are still working to understand exactly how it acts on the body. New research in mice now suggests that the drug may improve metabolism directly by activating brown adipose tissue, a form of fat that specialises in using energy rather than storing it.

According to the research team, the findings offer fresh insight into how tirzepatide works and could help shape the development of broader treatments for obesity and other metabolic disorders.

The study was led by Marion Peyrou, a Ramón y Cajal researcher at the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), the Sant Joan de Déu Research Institute (IRSJD) and the CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN).

A drug that targets two hormone receptors

Tirzepatide, the active ingredient in Mounjaro (also marketed as Zepbound), is approved for weight management in adults living with obesity, or with overweight alongside related health conditions. It is also approved for treating type 2 diabetes mellitus that is poorly controlled.

What sets tirzepatide apart from some other obesity medications is that it acts on the receptors for two hormonal factors at once: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This dual mechanism can lead to substantial weight loss, largely because the drug reduces how much a person eats.

For healthcare professionals supporting people who are prescribed tirzepatide and similar medicines, understanding these mechanisms is becoming increasingly relevant to everyday practice – an area explored in The College of Contemporary Health’s GLP-1RAs in Focus CPD course.

The researchers set out to establish whether tirzepatide also brings about metabolic changes that cannot simply be attributed to eating less.

How the study was designed

To answer this question, the team examined how the drug affected different fat deposits in an experimental mouse model, as this kind of detailed tissue analysis cannot readily be carried out in humans. Mice with obesity, which had been fed a high-fat diet, were treated with tirzepatide.

The researchers then compared these animals with a second group of mice that did not receive the drug but were given exactly the same amount of food. By matching food intake in this way, the scientists were able to separate the changes caused directly by tirzepatide from those that resulted from consuming fewer calories.

Tirzepatide activates brown fat

The analysis showed that tirzepatide activated brown adipose tissue. White adipose tissue mainly stores fat and tends to build up in people living with obesity, whereas brown fat specialises in using energy and “burning” the calories obtained from food.

“This activation is associated with an increased capacity to burn metabolic energy and with the production of batokines by brown adipose tissue, molecules that are beneficial for metabolism,” says Marion Peyrou.

The finding suggests that tirzepatide may influence metabolism in ways that go beyond the weight loss brought about by appetite suppression and reduced food intake.

“This drug not only reduces body weight, but also has beneficial effects on metabolism. Active brown adipose tissue ‘burns’ glucose and fat within the body, which would contribute to its positive effect not only in reducing body weight, but also in lowering blood glucose and fat levels, and improving metabolism,” the researcher points out.

Avoiding the pitfalls of earlier approaches

Scientists have long regarded brown fat activation as a potentially valuable strategy for treating obesity and other metabolic diseases. However, previous attempts to activate brown adipose tissue using drugs have frequently been unsuccessful because of unwanted side effects, particularly those affecting the heart.

“Tirzepatide, although it activates brown adipose tissue, does not have these negative effects; on the contrary, it shows cardiovascular benefits. If our findings are confirmed in humans, it would reinforce the importance of developing therapeutic strategies that not only reduce food intake but also increase energy expenditure and brown fat activation,” explains the researcher.

The results support the view that obesity treatments may be more effective when they act on several physiological processes at once, rather than focusing on appetite alone.

“This could help improve weight control and reduce associated disorders, such as type 2 diabetes and other metabolic disorders,” she adds.

Towards more personalised obesity treatment

A clearer understanding of how tirzepatide works could also influence how medicines in this class are prescribed in future.

“Identifying which patient profiles could benefit most, for example those with more compromised energy expenditure, would open the door to more personalised medicine, based not only on appetite or weight control, but also on overall metabolic status,” she emphasises.

Caution needed before applying the findings to people

The researchers are clear that because the findings come from mice, it cannot yet be assumed that tirzepatide acts in the same way in humans. Metabolism can differ considerably between the two species, as can the distribution of fat tissue and the way each responds to medications.

“As this is a study conducted on mice, we must be cautious, as there may be significant differences between species in terms of metabolism regulation, adipose tissue distribution and response to drugs. Therefore, we need more clinical evidence on the action of these drugs on fat in humans,” concludes Peyrou.

CCH insight

As research continues to reveal how dual GIP/GLP-1 receptor agonists such as tirzepatide act on the body – from appetite regulation to potential effects on energy expenditure – healthcare professionals need a confident, up-to-date understanding of these medicines to support the people in their care. The College of Contemporary Health’s GLP-1RAs in Focus CPD course offers a practical grounding in how these therapies work and how they fit into modern obesity and diabetes care.

Explore GLP-1RAs in Focus → 

Source: Biomedicine & Pharmacotherapy

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Poor Sleep Quality in Late Pregnancy Linked to Higher Obesity Risk in Children

Key Takeaways: 

• Mothers with poor sleep quality in late pregnancy had babies with lower weight in the first six months of life but higher weight at ages 1–2 years, with the effect strongest in male infants and babies born at term.
  
• In a study of 645 mother–child pairs, children whose mothers reported the worst sleep quality weighed 346.7 grams (12 ounces) more at age 1, with the greatest difference of 751.5 grams (1.7 pounds) observed at 17 months.
  
• Researchers suggest that incorporating sleep quality assessments into routine antenatal care could support early identification of at-risk pregnancies, and that addressing poor sleep could benefit the health of both mother and child.
  
  
  

Sleep in pregnancy and early childhood growth

New research has found that mothers who experienced poor sleep quality in late pregnancy had babies who weighed less during the first six months of life but more at ages 1–2 years. This effect was most pronounced in male infants and in babies born at term.

The findings, published in the American Journal of Preventive Medicine, suggest that incorporating sleep quality assessments into routine antenatal care could help healthcare professionals identify at-risk pregnancies earlier. The researchers also suggest that addressing poor sleep quality during pregnancy could benefit the health of both mother and child.

Two modifiable public health concerns

Sleep health in pregnancy and childhood obesity are both major, modifiable public health concerns. Global obesity rates among children and adolescents more than doubled between 1990 and 2022, and obesity now affects more than 390 million children aged 5–19.

Previous studies have found that poor sleep health is associated with a range of health conditions, including diabetes, obesity and cardiovascular disease. Both human and animal studies have also suggested that sleep quality during pregnancy may play a role in the intergenerational transmission of obesity risk from mother to child.

Rapid weight gain during infancy is a recognised risk factor for obesity in later childhood. Understanding how sleep health in pregnancy affects growth trajectories in early childhood could therefore help to mitigate its impact on children’s metabolic health.

Addressing gaps in the evidence

Much of the existing research in this area has been cross-sectional or has focused on children older than 2. In addition, the association between sleep health in pregnancy and childhood obesity has not been studied extensively in Hispanic populations in the US, who experience higher rates of overweight and obesity than other racial or ethnic groups.

How the study was conducted

The study examined 645 mother–child pairs from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) prospective pregnancy cohort in Los Angeles. Researchers assessed late-pregnancy sleep quality using the Jenkins Sleep Scale questionnaire.

Children’s height and weight were either measured during follow-up visits at the University of Southern California clinic or taken from medical records.

Sleep quality and infant weight

Most mothers in the study reported mild to moderate sleep disturbance, while 26% reported poor sleep quality.

Children whose mothers reported the worst sleep quality had lower weights from birth to 6 months, followed by higher weights thereafter. At age 1, the difference in weight was 346.7 grams (12 ounces). The greatest difference was observed at 17 months, at 751.5 grams (1.7 pounds).

The study highlights the importance of good sleep health during pregnancy. According to the researchers, the associations observed appear to be driven primarily by poor sleep quality in late pregnancy and are not explained by other traditionally identified prenatal and postnatal factors, such as feeding practices in childhood.

For healthcare professionals working with families, findings such as these reinforce the value of considering the earliest influences on a child’s weight. The College of Contemporary Health’s Childhood Obesity Essentials CPD course offers a useful grounding for clinicians looking to strengthen their understanding of childhood obesity and the factors that shape it.

Potential biological pathways

Senior author Carrie V. Breton, MPH, PhD, Professor at the Bursky School of Public Health, Washington University in St. Louis, and Adjunct Professor in the Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, said:

“Our research supports the notion that exposures during critical developmental windows of pregnancy can program offspring health.

“Several biological mechanisms may link late-pregnancy sleep health to children’s weight trajectories. For instance, poor sleep may affect maternal or child metabolic health programming, or both, which in turn could affect neonatal fat mass distribution and lead to abnormal lipid profiles or higher inflammation. Alternatively, stress pathways associated with higher childhood obesity risk may also play a role.”

Implications for antenatal care

Lead author Xiaoran Yang, MPH, a PhD graduate from the Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, added:

“Poor sleep health in pregnancy is common and often overlooked, and our findings suggest that monitoring it in routine prenatal care could be a simple and powerful step toward healthier growth for the next generation.”

CCH insight

Early life offers a crucial window for shaping a child’s long-term weight and metabolic health. Healthcare professionals who support families during pregnancy and early childhood are well placed to recognise risk factors early and help families take preventive steps. Build your confidence in this area with our Childhood Obesity Essentials CPD course. 

Explore Childhood Obesity Essentials →

Source: American Journal of Preventive Medicine

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Greater Weight Loss, More Side Effects: What GLP-1 RAs Mean for Women

Key Takeaways:

• Real-world studies show women treated with GLP-1 receptor agonists (GLP-1 RAs) report side effects such as headache, vomiting and dizziness more often than men, even though placebo-controlled trials suggest similar rates in both sexes.
  
• Women tend to lose more weight on GLP-1 RAs than men, while improvements in blood sugar control are comparable, possibly due to higher drug exposure, stronger suppression of food-motivated behaviours and interactions between GLP-1 signalling and oestrogen.
  
• The authors call for mandatory sex- and ethnicity-stratified trial reporting, more research across every stage of women’s lives, and equitable global access to genuine GLP-1 RAs, as nearly 80% of eligible adults live in low- and middle-income countries where access remains minimal.
  
  
  

A call to action on GLP-1 RA use in women

The second of a Series of papers presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (28 September – 2 October), and published in The Lancet Obstetrics, Gynaecology & Women’s Health, examines the wide-ranging issues surrounding GLP-1 RA use in women.

The authors, including Professor Paul Franks of Lund University and Helsingborg Hospital, Helsingborg, Sweden, and Professor Claire Meek of the Leicester Diabetes Research Centre and Leicester NIHR Biomedical Research Centre, Leicester, UK, alongside colleagues, issue a call to action to strengthen the evidence base for GLP-1 RA use in women worldwide.

The global burden of obesity among women

The prevalence of obesity is estimated to be slightly higher among women than among men, and this difference varies according to socioeconomic status. A recent analysis by the Global Burden of Disease group estimated that, in 2021, the global prevalence of overweight or obesity was 46.7% in females and 43.4% in males. Projections for 2050 rise to 60.3% and 57.4%, respectively.

This gender gap is more pronounced in low- and middle-income countries (LMICs), with the largest gaps seen in sub-Saharan Africa and south Asia. By contrast, men in high-income countries can have higher prevalence rates. The trend is likely to continue in the coming decades and is linked to socioeconomic inequalities, highlighting how broader social barriers disproportionately affect women in many regions of the world.

Why women may lose more weight on GLP-1 RAs

Weight loss with GLP-1 RAs is greater in women than in men, yet improvements in blood sugar control are comparable between the sexes. Several mechanisms could explain this greater weight-loss efficacy in women:

• Higher systemic drug exposure has been observed in women, even after adjusting for body mass.
  
• Women treated with GLP-1 RAs may experience enhanced suppression of food-motivated behaviours and greater inhibition of palatable food intake.
  
• Pre-clinical studies have highlighted possible interactions between GLP-1 signalling and oestrogen.
  
  
  

Side effects and weight regain

Real-world studies comparing adverse event rates in women and men treated with these medications have found a higher overall frequency of reported side effects among women, including increased rates of headache, vomiting and dizziness. This contrasts with placebo-controlled trials, which suggest similar rates in both sexes. The authors therefore stress that more studies are needed to quantify side-effect profiles in women and to develop strategies to mitigate them.

It is also well established that weight can be regained rapidly after GLP-1 RA treatment is stopped. Regaining fat without regaining additional muscle raises concerns about longer-term health and physical function in women, and further research is needed to ensure these powerful medications support women’s wellbeing over the long term.

Mental health and psychiatric safety

Trial data to date support the overall psychiatric safety profile of GLP-1 RAs, while reinforcing the importance of individualised risk assessment. Careful, routine screening for depression, anxiety and eating disorders is recommended for people of both sexes, both before treatment begins and during follow-up.

For healthcare professionals prescribing or supporting people on these medications, The College of Contemporary Health’s GLP-1RAs in Focus course offers a grounding in GLP-1 receptor agonist therapy, helping clinicians approach treatment decisions, monitoring and patient conversations with confidence.

Affordability and access in low- and middle-income countries

Independent manufacturing estimates suggest that semaglutide, for example, could be produced for less than $1 per month’s supply in oral form and $5 per month as an injection. However, recent analyses across 99 countries indicate that nearly 80% of adults who meet clinical eligibility criteria for GLP-1 RAs live in LMICs, where access remains minimal. In many of these settings, retail prices exceed $90 per month, placing treatment beyond the reach of women who rely on publicly funded care or out-of-pocket payments.

Diverse populations and polyendocrine metabolic ovarian syndrome

The paper explores multiple areas in which GLP-1 RAs affect women’s health, and highlights the need for further research in each. For example, many women with type 2 diabetes in LMICs are lean, and the BMI threshold at which type 2 diabetes begins to develop is often lower than for people of European ancestry. As a result, significant weight loss could have a more pronounced impact on these women.

Polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome) affects around 12% of women worldwide, with the highest rates in the eastern Mediterranean region and south-east Asia. Although weight loss leads to various health improvements in women with PMOS, GLP-1 RAs are not generally available or centrally funded for PMOS in most healthcare systems.

Research priorities across women’s lives

The authors conclude that extensive research into GLP-1 RA use in women is needed across a range of domains, including:

• mental health and eating disorders
• contraception, fertility and polyendocrine metabolic ovarian syndrome
• optimising pre-pregnancy health
• preventing complications
• safety during pregnancy and breastfeeding
• optimising health and body composition during menopause
• optimising cardiovascular health and preventing multimorbidity
• frailty and healthy ageing
  
  
  

The authors’ call to action

In their call to action, the authors say:

• “Women face the highest burden of obesity and its related complications, and should have access to high-quality, equitable, multidisciplinary obesity care worldwide”
  
• “Sex-stratified and ethnicity-stratified reporting of clinical trials related to GLP-1 receptor agonist use should be mandatory to facilitate future meta-analyses”
  
• “As the main users of GLP-1 receptor agonists and incretin-based therapies, women’s care should be guided by high-quality studies assessing their treatment’s efficacy and safety, specifically in conditions affecting women (eg, before, during, and after pregnancy)”
  
• “Existing access pathways to GLP-1 receptor agonists disadvantage women – to maximise the treatment’s benefits, companies, health-care funders, research funders, insurers, and policy makers should promote equitable access to high-quality, genuine GLP-1 RAs for women worldwide”
  

The authors conclude: “Tackling the global challenges in access to GLP-1 receptor agonists provides substantial opportunities to improve women’s health internationally. However, achieving equitable access will require coordinated action to strengthen supply chains, enhance regulatory vigilance against falsified and compounded products, and embrace innovative therapies – such as oral agents – that are stable, scalable, and potentially more affordable…Advancing women-centred obesity care demands targeted research, including trials inclusive of diverse ethnic groups, women of reproductive age, and LMIC populations, alongside women-focused cost-effectiveness and implementation studies.”

CCH insight

As GLP-1 RAs become central to obesity and diabetes care, understanding how they affect different groups, including women at different life stages, is increasingly important for safe, effective prescribing. Build your knowledge with our GLP-1RAs in Focus CPD course.

Explore GLP-1RAs in Focus – Why Drugs Like Ozempic Work →

Source: European Association for the Study of Diabetes

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AI Analysis of 400,000 Reddit Posts Reveals Underreported Side Effects of GLP-1 Medications

Key Takeaways:

• University of Pennsylvania researchers used artificial intelligence to analyse more than 400,000 Reddit posts from nearly 70,000 users discussing semaglutide and tirzepatide, identifying symptoms that may be underrepresented in clinical trials and official regulatory information.
  
• Reproductive symptoms, including menstrual irregularities, and changes in body temperature, such as chills and hot flashes, emerged as signals particularly worth investigating, alongside fatigue, which was the second most frequently reported complaint.
  
• The findings show associations in what people discussed online, not proof that GLP-1 medications cause these symptoms, but the researchers suggest “computational social listening” could become a fast, early detection system for emerging drug safety concerns.
  
  
  

Listening to patients at scale

Artificial intelligence is offering researchers a new way to hear what patients are saying about widely used GLP-1 medications. After analysing more than 400,000 Reddit posts, a team at the University of Pennsylvania identified several symptoms reported by people using semaglutide (Ozempic, Wegovy and Rybelsus) and tirzepatide (Mounjaro and Zepbound) that may not be fully reflected in clinical trials or official regulatory information.

The study, recently published in Nature Health, examined more than five years of posts from nearly 70,000 Reddit users. Two categories of symptoms stood out as particularly deserving of further investigation: reproductive symptoms, including changes to menstrual cycles, and problems relating to body temperature, such as chills and hot flashes.

Importantly, the findings do not establish that the medications caused these symptoms. Rather, the researchers say that this vast collection of spontaneous patient reports may reveal signals that merit closer examination.

“Some of the side effects we found, like nausea, are well known, and that shows that the method is picking up a real signal,” says Sharath Chandra Guntuku, Research Associate Professor in Computer and Information Science (CIS) at Penn Engineering and the study’s senior author. “The underreported symptoms are leads that came from patients themselves, unprompted, and clinicians could potentially pay attention to them.”

What patients report outside clinical trials

Clinical trials are designed to determine whether treatments work and to identify significant safety problems. However, they cannot necessarily capture every symptom that matters to patients once a medication is being used by a much larger and more varied population.

“Clinical trials generally identify the most dangerous side effects of drugs,” adds Lyle Ungar, Professor in CIS and a co-author on the study. “But they can fail to find what symptoms patients are most concerned about; even though social media is not necessarily representative, a large collection of posts may reflect additional concerns.”

This distinction is an important one. The study identified associations in what people discussed online, not evidence that GLP-1 medications were responsible for those experiences.

“We can’t say that GLP-1s are actually causing these symptoms,” notes Neil Sehgal, the study’s first author and a doctoral student in CIS advised by Guntuku and Ungar. “But nearly 4% of the Reddit users in our sample reported menstrual irregularities, which would be even higher in a female-only sample. We think that’s a signal worth investigating.”

Using social media as an early health signal

The idea of mining online conversations for clues about drug safety predates the current AI boom. In 2011, Ungar took part in one of the earliest efforts to use content created by internet users to identify possible adverse effects of medications.

Social media can capture experiences that patients discuss with one another but may never formally report to a doctor, drug manufacturer or regulator.

“Online patient communities work a lot like a neighborhood grapevine,” says Ungar. “People who are living with these medications are swapping notes with each other in real time, sharing experiences that rarely make it into a doctor’s office visit or an official report.”

Since then, online patient communities have grown enormously. This has made social media a potentially valuable source for understanding how medications affect people in everyday life, although gaining access to platform data has become more difficult.

The researchers emphasise that traditional clinical research remains essential, but online conversations can provide information far more quickly when millions of people begin using a medication.

“Clinical trials are the gold standard, but by design, they are slow,” says Guntuku. “This is not a replacement for trials, but it can move much faster, and that speed matters when a drug goes from niche to mainstream almost overnight.”

How AI makes large-scale analysis possible

One of the biggest obstacles to this kind of research has always been scale.

Guntuku describes the approach as “computational social listening”, which uses computational methods to identify patterns across large collections of online conversations about health.

Patients, however, rarely describe their symptoms using standardised medical terminology. One person might describe feeling unusually cold, another might mention constant chills, while a clinician could categorise both experiences using a specific medical term.

Researchers therefore need a way to translate everyday language into standardised categories. One important reference is the Medical Dictionary for Regulatory Activities (MedDRA), which provides terminology widely used to classify medical conditions, symptoms and adverse events.

Previously, matching vast numbers of informal social media posts to standardised medical terminology required an enormous amount of work, limiting how much data researchers could realistically analyse.

Large language models such as GPT and Gemini are changing that, allowing researchers to process and categorise huge volumes of text more quickly and consistently.

“Large language models have made it possible to do this kind of analysis much faster with a level of standardization that could be difficult to achieve before,” says Sehgal.

Unexpected symptoms emerge from 400,000 posts

The researchers stress that Reddit users do not represent the wider population of people taking GLP-1 medications. Reddit users tend to be younger, are more likely to be male and are disproportionately based in the United States.

Despite this limitation, the analysis produced a reassuring sign that the approach was detecting genuine patterns: many of the symptoms discussed by Reddit users closely matched the already known effects of semaglutide and tirzepatide.

Around 44% of users included in the study described at least one side effect. Gastrointestinal problems were the most common, consistent with the nausea and other digestive issues already associated with these medications.

More intriguing were symptoms that appeared frequently enough to attract the researchers’ attention but may not be as well represented in current drug labels or conventional adverse event reports:

• Reproductive symptoms: nearly 4% of users who reported side effects described reproductive symptoms, including changes to menstruation such as bleeding between periods, heavy bleeding and irregular menstrual cycles.
  
• Body temperature changes: users described chills, feeling unusually cold, hot flashes and symptoms resembling a fever.
  
• Fatigue: this was the second most frequently reported complaint in the Reddit data, even though relatively few clinical trials reported fatigue often enough for it to meet established reporting thresholds.
  

For healthcare professionals prescribing or supporting people using these medications, findings like these are a reminder of the value of asking open questions about how patients are feeling, beyond the side effects most commonly discussed. Clinicians wishing to build confidence in this area may find The College of Contemporary Health’s GLP-1RAs in Focus CPD course a useful way to deepen their understanding of these therapies and the conversations that surround them.

Why menstrual and temperature changes are of interest

One possible reason these reports caught the researchers’ attention involves the hypothalamus, a small but vitally important region of the brain. Among its many roles, the hypothalamus helps regulate hunger, hormones, reproduction and body temperature.

“These drugs are thought to work by engaging part of the brain called the hypothalamus, which helps regulate a wide variety of hormones,” says Jena Shaw Tronieri, Senior Research Investigator at Penn’s Center for Weight and Eating Disorders and a co-author of the study. “That doesn’t mean the medications are necessarily causing these symptoms, but it could suggest that reports of menstrual changes and body temperature fluctuations are worth studying more systematically.”

The researchers are not suggesting that this biological link proves GLP-1 medications are responsible. Instead, it provides a further reason to test these patient-reported patterns more rigorously through controlled research.

Turning online conversations into research leads

For now, the team hopes the results will encourage scientists and clinicians to pay closer attention to the symptoms that patients repeatedly discuss online.

“They’re clearly on patients’ minds, and that’s worth paying attention to,” says Sehgal.

The researchers also plan to extend their analysis beyond Reddit and beyond English-language communities. Doing so could help determine whether the same patterns emerge among different groups of people and across different social media platforms.

“We don’t really know yet whether what we’re seeing on Reddit reflects the experience of GLP-1 users globally, or whether it’s particular to the kind of person who posts on Reddit in the United States,” Ungar says.

An early warning system for emerging health concerns

In the longer term, rapid AI analysis of online patient conversations could become an early detection system for emerging health concerns involving medications, supplements and wellness products.

This could be especially valuable for substances that gain popularity online faster than conventional research can keep pace. Loosely regulated or unregulated products, including injectable peptides, can spread rapidly through communities on Reddit, TikTok and other platforms, meaning that discussions among users may offer some of the earliest indications of unexpected effects.

“The whole point of this kind of approach is that it can move quickly, and that’s exactly when it’s most valuable,” says Guntuku.

The study was conducted at the University of Pennsylvania School of Engineering and Applied Science. The authors report no outside funding. Tronieri reports receiving an investigator-initiated grant, on behalf of the University of Pennsylvania, from Novo Nordisk, and receiving consulting fees from Currax Pharmaceuticals, LLC. The other authors report no conflicts of interest.

CCH insight

As more people use GLP-1 medications, healthcare professionals are increasingly hearing about experiences that go beyond the most familiar side effects. Understanding how these therapies work, and how to have informed, supportive conversations with patients about what they are experiencing, is becoming an essential part of practice.

GLP-1RAs in Focus from The College of Contemporary Health is designed to help healthcare professionals strengthen their knowledge of GLP-1 receptor agonists and support patients with confidence.

Explore GLP-1RAs in Focus today → 

Source: University of Pennsylvania School of Engineering and Applied Science

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GLP-1 Medications Linked to Nutritional Deficiencies in Children and Young People, Study Finds

Key Takeaways: 

• Nearly one in six children and young people (16.8%) prescribed GLP-1 medications for weight loss, prediabetes or type 2 diabetes were diagnosed with a nutritional deficiency within the first year of treatment, with vitamin D deficiency the most common (12.4%).
  
• Only 5% of patients received nutritional counselling within 30 days of starting a GLP-1 medication, and fewer than 25% received it within six months.
  
• Researchers are calling for proactive nutritional management from the outset of GLP-1 treatment in children, rather than waiting until a deficiency is diagnosed.
  
  
  

Nutritional risks during a critical stage of development

Children and young people prescribed GLP-1 medications for weight loss, prediabetes or type 2 diabetes are at risk of developing nutritional deficiencies, according to new research from scientists at Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago. The study found that nutritional deficiencies were diagnosed in nearly one in six patients (16.8%) within the first year of treatment.

Vitamin D deficiency was the most frequently identified, affecting 12.4% of children within one year of starting GLP-1 treatment.

The findings were recently published in the journal Childhood Obesity, in a study titled “Nutritional Deficiencies, Complications, and Nutrition Therapy/Counseling in Pediatric Patients Using GLP-1 Receptor Agonists.”

Why adolescence matters

The study’s senior author, Justin Ryder, associate professor of surgery and paediatrics at Northwestern University Feinberg School of Medicine and vice chair of research for the department of surgery at Lurie Children’s, emphasised the importance of understanding these risks as GLP-1 use in younger patients grows.

“As appropriate pediatric use of GLP-1s becomes more widespread, we need to understand the risks during periods of rapid growth and pubertal development,” said Ryder. “Nutrients such as vitamin D, iron and calcium are of particular concern during adolescence, when deficiencies may have lasting implications for skeletal health and overall development.”

A significant gap in nutritional support

Despite these risks, the research revealed that very few children received nutritional support after beginning treatment.

“Nutritional support needs to play a critical role once treatment with a GLP-1 medication is initiated,” he said. “In our study, however, we found that only 5% of patients received nutritional counseling within 30 days of GLP-1 treatment and less than 25% received nutritional counseling within 6 months.”

The gap highlights the need for healthcare professionals working with children and young people living with obesity to consider nutrition as an integral part of care from the moment treatment begins. Clinicians looking to strengthen their understanding in this area may find structured training, such as The College of Contemporary Health’s Childhood Obesity Essentials course, a valuable way to build confidence in supporting this patient group.

How the study was conducted

The researchers analysed national administrative claims data from 2017 to 2022, covering more than 100 million patients. From this dataset, they identified 2,031 young people aged 10–17 years who were using GLP-1 medications, met continuous enrolment criteria and had no prior diagnosis of a nutritional deficiency.

Within this sample, the most commonly prescribed GLP-1 medications were:

• Liraglutide (78.6%)
• Dulaglutide (10.4%)
• Semaglutide (9.1%)
  
  
  

A call for proactive nutritional management

The research team hopes the findings will encourage a shift towards preventive nutritional care for children and young people receiving GLP-1 treatment.

“We hope that our study findings bring much-needed recognition to the importance of proactive nutritional management when GLP-1s are prescribed to children, as opposed to waiting until a nutritional deficiency is diagnosed,” Ryder said. “Knowing the risks, we are in a much better position to prevent harm to children treated with GLP-1s during a pivotal period in their lives.”

Funding for the study was provided by Abbott.

CCH insight

As GLP-1 medications become more widely used in younger patients, healthcare professionals need the knowledge and skills to support children and young people living with obesity safely and holistically, including their nutritional needs during growth and development. Our Childhood Obesity Essentials CPD course is designed to help clinicians deliver confident, evidence-informed care for this patient group.

Explore Childhood Obesity Essentials and enrol today → 

Source: Northwestern University

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New Virtual Care Programme Aims to Transform Severe Obesity Management in Western Sydney

Key Takeaways: 

• Nepean Blue Mountains Local Health District (NBMLHD) is building “Living Well Virtual Care”, a 12–18 month virtual programme offering evidence-based, multidisciplinary care to adults living with severe obesity in Western Sydney.
  
• The programme is modelled on the internationally recognised Family Metabolic Health Service (FMHS) adult model of care and is designed for people who face barriers attending hospital-based services, including long travel distances, physical disabilities or severe anxiety.
  
• Funded through NSW Health’s Translational Research Grants Scheme and supported by the Agency for Clinical Innovation, Living Well has been designed to be scalable across NSW, including in regional and rural communities.
  
  
  

A new digital pathway for severe obesity care

Nepean Blue Mountains Local Health District (NBMLHD) is building the “Living Well Virtual Care” programme, a new digitally enabled clinical pathway designed to improve access to evidence-based severe obesity management in Western Sydney.

Living Well will run as a 12–18 month virtual programme. It draws its inspiration from the successful and internationally recognised Nepean Blue Mountains Family Metabolic Health Service (FMHS) adult model of care.

The programme supports adults living with severe obesity through a holistic, evidence-based, multidisciplinary approach. This approach addresses not only a person’s physical and mental health, but also the social factors that influence their long-term wellbeing.

Extending the reach of an established service

A central aim of Living Well is to reach people who may currently be missing out on specialist care.

“Living Well will allow us to extend the reach of the Family Metabolic Health Service to people who are waiting long periods of time to see us, or who may otherwise never engage with us,” explains Dr Kathryn Williams, Clinical Lead of the Family Metabolic Health Service and Principal Investigator of the Living Well program.

The programme is particularly suited to people who face barriers attending hospital-based services. These include people who live long distances from clinics, people with physical disabilities and people who experience severe anxiety.

Responding to growing demand across NSW

Demand for public obesity services continues to grow across NSW. Without timely intervention, a person’s health and quality of life can deteriorate, increasing the risk of chronic disease, disability and future hospitalisations.

Living Well has been developed as an affordable, scalable response to this challenge. By offering earlier, virtual access to coordinated care, the programme aims to support better health optimisation and ease pressure on emergency departments and inpatient services. These are outcomes that the in-person Family Metabolic Health Service model of care is already delivering.

“Severe obesity is a complex, chronic condition and it requires sustained, coordinated care,” continues Kathryn.

“Living Well will put the right support in place earlier, improving health outcomes for patients while also delivering better value for the health system.”

For healthcare professionals, this emphasis on obesity as a complex, chronic condition requiring sustained and coordinated care reflects the kind of evidence-based foundation covered in The College of Contemporary Health’s Obesity Essentials course, which supports clinicians to strengthen their understanding of obesity management in practice.

What the programme offers

The Living Well Virtual Care programme brings together a range of digital and supportive elements, including:

• On-demand educational content
• Live webinars and group interventions
• Practical resources to support participants to engage their GP in medical weight management and the management of obesity-related complications
• Links to trusted external online resources relevant to severe obesity
• Opportunities for peer connection and support

Alongside engaging with the online content, participants receive one-to-one health coaching.

Designed to scale across the state

Living Well has been designed to be scalable across NSW, including in regional and rural communities, and is supported by the Agency for Clinical Innovation.

“This program will demonstrate how digital care can be used as an extension of high-quality clinical services,” says Kathryn.

“For many patients it will mean timely access to care, greater confidence in managing their health, and a more positive experience as they journey through the health system.”

Funding and research significance

The Living Well Virtual Care Program is funded through NSW Health’s Translational Research Grants Scheme. It is one of three NBMLHD high-impact research projects with the potential to be translated into policy and practice and to build research capability within NSW Health.

CCH insight

As services like Living Well show, effective care for people living with severe obesity depends on clinicians who understand obesity as a complex, chronic condition and can support people through sustained, coordinated care. The College of Contemporary Health’s Obesity Essentials course is designed to help healthcare professionals build confidence in evidence-based obesity management.

Explore Obesity Essentials → 

Source: Nepean Blue Mountains Local Health District

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Beyond the Scales: New Research Asks Whether GLP-1 Medications Change Daily Life

Key Takeaways:

• A new National Bureau of Economic Research working paper found little evidence that GLP-1 medications produced measurable changes in mental health, self-rated health, employment or marital status among adults living with diabetes.
  
• Apparent differences between people taking the medications and those who were not largely disappeared once researchers followed the same individuals over time, suggesting the gaps reflected who takes these drugs rather than what the drugs do.
  
• The findings do not call the clinical value of GLP-1 medications into question: improved glycaemic control, weight loss and better physical health remain the clearest measurable benefits.
  
  
  

A familiar class of medicines, a less familiar question

GLP-1 medications such as Ozempic have reshaped the treatment of Type 2 diabetes. For many people, they help bring blood sugar under control, lower cardiovascular risk and produce substantial weight loss. Those outcomes are now supported by a large and growing body of clinical evidence, and they have made this class of medicines one of the most closely watched developments in contemporary healthcare.

What remains far less certain is whether those physical health improvements ripple outwards into the rest of a person’s life. Do they translate into better mental health? More stable employment? Stronger or more enduring relationships? Researchers are only beginning to test those assumptions, and the answers matter well beyond the consulting room.

What the researchers set out to examine

A new National Bureau of Economic Research working paper takes up precisely that question. The study was conducted by Robert Kaestner, an economist and research professor at the University of Chicago Harris School of Public Policy, alongside co-author Cuiping Schiman.

Among adults with diabetes, the researchers found little evidence that using GLP-1 medications produced measurable changes in mental health, self-rated health, employment or marital status.

“We know these drugs improve health outcomes, and there’s been a great deal of research documenting those benefits,” said Kaestner, a research professor. “What hadn’t really been examined was whether those improvements extended into other parts of people’s lives.”

Why the question matters for coverage decisions

The issue is becoming increasingly important as insurers and government programmes weigh up whether to broaden access to GLP-1 medications. The medical case is already well documented. What is far less clear is whether these treatments also generate social or economic gains that might strengthen the argument for wider coverage.

That distinction is not merely academic. If GLP-1 medications were shown to help people return to work, sustain relationships or experience meaningful improvements in psychological wellbeing, the calculation around funding and eligibility would look rather different. If they do not, decisions will continue to rest primarily on the clinical evidence.

How the study was designed

To investigate, Kaestner and Schiman drew on more than ten years of data from the Medical Expenditure Panel Survey, a nationally representative survey. Their analysis focused on adults with diabetes between 2012 and 2023.

Crucially, the researchers did not rely solely on comparing people who used GLP-1 medications with those who did not. Instead, they followed the same individuals over time. This within-person approach allowed them to observe whether a person’s circumstances actually changed after starting treatment, rather than simply noting how two different groups of people happened to differ.

The team examined several indicators of wellbeing, including symptoms of depression, psychological distress, self-rated health, employment and marital status.

At first glance, people taking GLP-1 medications did appear to differ from those who were not, particularly in relation to employment and marriage. Those differences, however, mostly disappeared once the researchers tracked changes within the same individuals over time.

That pattern points to an important interpretive lesson. The original gaps may well have reflected differences between the kinds of people who take GLP-1 medications and those who do not, rather than any effect caused by the medications themselves. It is a distinction that is easy to lose in headline findings, and one that clinicians are increasingly being asked to explain to the people in their care.

Few measurable changes outside physical health

The results held steady across different time horizons. Whether the researchers looked at people after roughly one year of GLP-1 use or followed them across a longer two-year period, the picture was much the same. In both cases, they found little evidence that taking the medications led to meaningful changes in the broader life outcomes they measured.

Kaestner was careful to stress that this is not the same as proving GLP-1 medications have no effects beyond physical health. Some changes may simply be more subtle, or harder to capture with the measures available.

“We measured outcomes like whether someone became employed or unemployed, whether they got married or divorced, and standard indicators of mental health,” he said. “Those are important measures, but they don’t necessarily capture changes in self-esteem, relationship quality, or other day-to-day experiences.”

In other words, the study was well placed to detect large, discrete shifts in a person’s circumstances. It was less able to register the quieter changes that people themselves often describe as the most significant: feeling more confident, moving through the world with greater ease, or relating differently to food and to other people.

The medical benefits remain well established

The researchers were equally clear that their findings do not undermine the medical value of GLP-1 medications. For adults with diabetes, Kaestner noted, the clearest measurable benefits remain those already demonstrated in clinical research, including improved glycaemic control, weight loss and better physical health.

This is the balance clinicians are increasingly asked to strike in practice: conveying genuine confidence in the clinical evidence while setting realistic expectations about what a medication can and cannot be expected to change. Practitioners looking to strengthen that footing often turn to structured CPD, such as the College of Contemporary Health’s GLP-1RAs in Focus short course, which examines the evidence base underpinning this class of medicines and how it translates into everyday clinical conversations.

A young and expanding field of research

As GLP-1 medications are prescribed more widely beyond diabetes, and become increasingly common in weight management, researchers will have far more opportunity to test whether broader social effects emerge in other populations or over longer follow-up periods.

“This is still a very new area of research,” he said. “As use continues to grow, understanding these broader consequences will become increasingly important for patients, clinicians, and policymakers alike.”

For now, the evidence suggests a more measured conclusion than the surrounding public conversation often implies. GLP-1 medications can meaningfully change a person’s physical health. Whether, and how, they change a person’s life is a question the research is only starting to ask.

CCH insight

Supporting people prescribed GLP-1 receptor agonists calls for a clear grasp of the evidence, including its limits. GLP-1RAs in Focus, a CPD-accredited short course from the College of Contemporary Health, is designed for healthcare professionals who want a confident, evidence-informed foundation in this rapidly developing area.

Explore GLP-1RAs in Focus →

Source: University of Chicago Harris School of Public Policy

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Obesity May Not Just Drive Breast Cancer – It May Remove a Natural Defence

Key Takeaways: 

• Researchers at Huntsman Cancer Institute at the University of Utah have identified a lipid, 9S-HODE, that is produced in far greater quantities by lean fat cells in the breast than by fat cells affected by obesity – and that helps drive cancerous cells towards their own destruction.
  
• The finding reframes the relationship between obesity and breast cancer: rather than obesity simply adding a harmful influence, it may also remove a protective one that the body would otherwise supply for itself.
  
• In preclinical mouse models, restoring 9S-HODE levels in fat cells affected by obesity suppressed breast tumour growth, pointing towards a potentially feasible therapeutic route that works with the body’s existing biology.
  
  
  

A shift in how obesity and cancer risk are understood

A research team at Huntsman Cancer Institute at the University of Utah (the U) has found that obesity prevents a biological process that kills cancerous cells, revealing a possible reason why obesity is a risk factor for breast cancer.

The distinction matters. For years, research into obesity and cancer has largely asked what obesity adds to the picture – inflammation, altered hormone signalling, metabolic disruption. This study asks a different question: what does obesity take away?

“We uncovered the role of a molecule that normally appears in lean tissue that restrains breast cancer growth but is less present with obesity. We know obesity is often a driver of breast cancer, and researchers in our field usually consider how obesity is promoting the disease. But we hadn’t really considered that obesity could also be the loss of something that naturally protects us.” – Keren Hilgendorf, PhD, Huntsman Cancer Institute investigator, assistant professor of biochemistry, University of Utah, and senior author of the study

Hilgendorf and first author Meghan Curtin, doctoral candidate in molecular biology at the U, have published the transformative results of their research in the prestigious journal Science.

Why breast tissue is a special case

Breasts are mostly composed of fat, particularly fat cells called adipocytes. These adipocytes are different depending on a person’s weight and can be lean or obese. In obesity, adipocytes are larger than in their lean counterparts. Hilgendorf also says that the two types of adipocytes generate distinctive microenvironments for cancer cells.

That last point is the crux of the work. Adipocytes are not inert padding around the glandular tissue of the breast – they are metabolically active cells that shape the chemical environment in which any developing cancer must survive. Two people can therefore have breast tissue that looks superficially similar but that behaves very differently at a molecular level, depending on the state of the fat cells within it.

Identifying 9S-HODE

In preclinical models, including breast tissues from donors, Hilgendorf and Curtin found that one of those key differences is the production of a lipid, or fatty acid, known as 9S-HODE.

9S-HODE plays an important role in promoting cell death, particularly a kind of cell death called ferroptosis. This is one way the body purges old and damaged cells, including cells that could be cancerous.

Ferroptosis is, in effect, part of the body’s routine quality control. Cells that are damaged or behaving abnormally are cleared before they can cause harm. A tissue environment that supports ferroptosis is therefore a hostile one for early cancerous cells; an environment that does not support it is considerably more permissive.

What the lean and obese microenvironments do differently

“We found that the lean adipocytes produce much more 9S-HODE than obese ones. This means that cancerous cells die more readily in lean tissue,” says Curtin. “By producing more 9S-HODE, our bodies are actively protecting us, under lean circumstances, in a way it cannot with obesity.”

In other words, the protective mechanism is not switched off entirely in people living with obesity – it is diminished. The supply of the lipid that helps push cancerous cells towards ferroptosis falls away, and with it one of the local defences that breast tissue would otherwise mount on its own behalf.

Restoring the lost signal in preclinical models

In their preclinical mouse models, Hilgendorf and Curtin found that increasing the amount of 9S-HODE in obese adipocytes suppressed breast cancer tumour growth. They believe this new understanding could lead to better therapies.

This is the step that moves the work from observation to intervention. Demonstrating that a molecule is absent is one thing; demonstrating that putting it back changes the trajectory of tumour growth is another, and it is what gives the finding its clinical interest.

“From a clinical perspective, this discovery is incredibly empowering. Because 9S-HODE is naturally present in the body but is lost with obesity, we may be able to restore this protection by putting it back,” says Hilgendorf. “That could become a very feasible therapeutic approach to slow breast cancer growth.”

A therapy built on replacing something the body already makes is, in principle, a more tractable proposition than one built on introducing an entirely foreign agent – though that remains a possibility to be tested rather than an established treatment.

Important caveats

Hilgendorf and Curtin recognize that obesity is just one factor that contributes to breast cancer and that the disease can develop for other reasons. They also say that 9S-HODE seems to be primarily produced by fat cells in the breast, though other fat cells throughout the body may have a similar protective function that will require more research.

Two limits are worth holding onto. First, breast cancer is multifactorial, and no single mechanism accounts for an individual’s risk. Second, the 9S-HODE signal appears to be a local one, generated by fat cells within the breast itself – whether adipose tissue elsewhere in the body performs a comparable protective role for other cancers is an open question.

For clinicians who support people living with obesity, findings of this kind reinforce why obesity is increasingly framed as a complex chronic disease with wide-ranging physiological consequences rather than a matter of body weight alone – the understanding that underpins CCH’s CPD short course Obesity Essentials, which examines the biology, drivers and clinical management of obesity across the care pathway.

What comes next

“We believe this shift in the understanding of the roles of lean and obese adipocytes is the start of something. This is just one discovery, and it’s not the end of the road,” says Curtin. “This opened our eyes to new ways to think about science, and hopefully we can harness what our bodies are already doing to make progress against this disease.”

The critical research happening every day at Huntsman Cancer Institute is supported by the National Institutes of Health/National Cancer Institute, including cancer center support grant P30 CA042014, as well as Huntsman Cancer Foundation.

CCH insight

Research like this is changing how obesity is understood at a cellular level – and with it, how healthcare professionals discuss risk, prevention and treatment with the people in their care. CCH’s Obesity Essentials CPD short course gives clinicians a grounded, evidence-based foundation in the science and clinical management of obesity as a chronic disease.

Explore Obesity Essentials → 

Source: Huntsman Cancer Institute at the University of Utah

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Scientists Identify the Biological Memory That Makes Obesity Relapse So Hard to Prevent

Key Takeaways: 

• Researchers have identified a lasting biological change in fat cells – an “obesity memory” – that keeps the appetite-stimulating hormone asprosin elevated even after a person or animal has lost the excess weight.
  
• The same inflammatory signal can cross the placenta, programming a baby’s fat cells before birth and offering a molecular explanation for why obesity risk can pass from mother to child across generations.
  
• Blocking the asprosin pathway in mice prevented both weight regain after dieting and inherited obesity risk, suggesting a potential complementary target to use alongside or after GLP-1 receptor agonist treatment.
  
  
  

Two long-standing puzzles in obesity research

Two biological mysteries have resisted explanation for decades. The first is why almost everyone who loses weight eventually regains it, regardless of the method used to lose it. The second is why obesity is transmitted from mother to child at rates that diet and environment alone cannot account for. Scientists from the Harrington Discovery Institute at University Hospitals and Case Western Reserve University now believe they have identified the reason behind both.

In a study published in Cell Reports, the research team found that obesity produces a durable biological change within fat cells that keeps the hunger hormone asprosin elevated – a phenomenon the researchers describe as “obesity memory” – even once weight has been lost. The findings may help to explain why many people regain weight after dieting or after discontinuing GLP-1 medications, and why obesity risk can persist from one generation to the next.

An appetite signal stuck in the on position

“Imagine having an appetite-stimulating signal stuck in the ‘on’ position day after day, despite losing weight,” explained Atul Chopra, M.D., Ph.D., senior author of the study, investigator and associate director of the Harrington Rare Disease Program at Harrington Discovery Institute at UH, and associate professor of medicine, genetics and genomics at Case Western Reserve University School of Medicine.

“Our findings suggest one reason weight regain can be so difficult to prevent after treatment ends. This same signal can also cross the placenta from mother to baby. The result is a child born with a programmed susceptibility to obesity. This may also explain why obesity became an epidemic and why the cycle has continued for generations.”

The observation that weight regain and intergenerational risk are near-universal features of obesity is not new. What has been missing is the underlying molecular explanation.

“These patterns have been observed for decades, but nobody knew the exact molecular mechanism that makes obesity so persistent or how it transmits across generations,” Chopra added. “We wanted to find the biological basis for that persistence.”

A switch that stayed on

The team began the study by looking for what turns up production of the hunger hormone asprosin in obesity. They identified an inflammatory signal, TGF-β1, as the trigger. The most striking result was that only a brief exposure to that signal was required to create a lasting change, one that persisted for weeks after the signal itself had disappeared.

“It was like flipping a light switch that stays on even after you remove your finger,” Chopra said. “Even after mice lost all the excess weight and TGF-β1 returned to normal, this switch in their fat cells remained flipped, keeping asprosin and appetite elevated.

“This gives us a molecular explanation for why GLP-1 drugs, which suppress appetite while you take them, cannot fix the underlying biological memory that drives hunger back up once treatment ends. This same signal crosses the placenta and programs a baby’s fat cells before birth.”

In other words, the change in fat tissue is epigenetic rather than temporary. The cells retain a record of the obesity they were exposed to, and that record continues to drive hunger long after body weight has normalised.

What this means for GLP-1 therapy

The mechanism offers an explanation for a pattern already familiar to clinicians: people taking GLP-1 medications frequently regain weight once they discontinue treatment. The medication suppresses appetite for as long as it is taken, but it does not erase the epigenetic memory held in fat cells. When the pharmacological brake is released, the underlying appetite signal is still switched on.

This has practical implications for how GLP-1 therapy is planned, discussed and supported in practice, particularly around the point of discontinuation. Structured professional development in this area – such as the College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme short course – can help clinicians set realistic expectations with patients from the outset and plan for the period after treatment ends, rather than treating regain as an unexpected failure.

Pharmaceutical companies are actively searching for ways to help people maintain weight loss once treatment stops. The new findings identify a potential complementary target: a pathway that may sustain the biological drive towards regain after weight reduction.

Blocking asprosin changed the outcome

The researchers also tested what happened when the asprosin pathway was interrupted in mice, from the gene that produces the hormone through to the receptor in the brain that responds to it. Blocking this pathway prevented both weight regain after dieting and the inherited obesity risk passed to offspring.

That result points towards new therapeutic strategies aimed directly at the relapse problem that drug developers are currently trying to solve.

Evidence beyond a single laboratory

The study was deliberately designed to test its central observation outside the laboratory that made it. A separate laboratory led by Seth J. Field, M.D., Ph.D., independently reproduced the key persistence finding. Field is director of physician-scientist programs and chief scientific officer at the Harrington Discovery Institute at UH and a professor at Case Western Reserve School of Medicine.

Analyses of publicly available mouse and human datasets produced further supporting evidence. Additional human research is still needed, but the convergence across separate laboratories and independent datasets strengthens the case that this mechanism warrants serious investigation.

A message for clinicians

Chopra said the central message for clinicians is that obesity relapse is not a failure of willpower or discipline. It is driven by a durable biological memory written into fat tissue, which sustains hunger long after the weight has come off.

“We need to treat obesity as a condition that leaves lasting biological scars, not just a temporary state of excess weight,” he said.

Framing obesity in these terms has consequences for how conversations with patients are conducted. If regain reflects a persistent biological signal rather than a lapse in personal effort, then the clinical focus shifts towards long-term management and realistic planning for the period after active treatment.

Turning to human trials

The critical next step is translating these findings into people. The researchers plan to confirm that the same epigenetic memory operates in human fat tissue after weight loss, and to test whether therapies that block asprosin, or that reset these epigenetic marks, can prevent weight regain in people.

“Given the need for durable obesity treatments, we are interested in whether asprosin-blocking therapies could be used alongside or after GLP-1 treatment to prevent rebound,” Chopra concluded.

CCH insight

This could be a very significant breakthrough in our understanding of weight regain and our ability to do something about it. We have known for a while that obesity results in a number of epigenetic changes in adipocytes (fat cells) which remain after weight loss, and are believed to drive weight regain, but we don’t yet have the technology to reverse these changes. By identifying asprosin as a major player in this drive to regain weight, we now have a very realistic target for new therapeutic strategies. There is a long way to go, but this could be a milestone in the battle against weight regain.

Research of this kind is changing how weight regain is understood and discussed in the consultation room. The College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme CPD short course is designed for healthcare professionals who prescribe or support people using GLP-1 receptor agonists, including the practical questions that arise around initiation, ongoing support and discontinuation.

Explore GLP-1RA Therapy: The Complete Programme →

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Maternal Fruit and Vegetable Intake Linked to Lower Childhood Obesity Risk

Key Takeaways: 

• Higher maternal fruit and vegetable intake during pregnancy was associated with lower odds of overweight or obesity in children at four years of age.
  
• Commercial fruit juice intake was linked to higher odds of these outcomes, though the authors classed this as exploratory. Natural and total juice showed no association.
  
• The study was observational and relatively small, so it cannot establish cause and effect.
  
  
  

Why prenatal nutrition is under the spotlight

Maternal diet shapes offspring development from the earliest stages of gestation. A recent study published in the journal Nutrients reports that higher maternal fruit and vegetable intake during pregnancy was associated with lower odds of overweight or obesity in children at four years of age. In contrast, overweight and obesity were more common among children whose mothers reported higher intakes of commercial fruit juices, though not natural fruit juices. The authors were careful to frame this second result as exploratory.

Childhood obesity has risen steadily across the world over recent decades, and Spain records the second-highest prevalence among European nations. The associations between paediatric obesity and a range of adverse physical and psychosocial outcomes are well documented in the literature.

That trajectory has prompted growing interest in preventive strategies that begin before birth. Maternal diet during pregnancy is considered particularly influential because it helps determine the intrauterine environment and may shape fetal metabolic programming, with potential consequences for the child’s long-term risk of obesity.

Greater adherence to healthy dietary patterns in pregnancy has been associated with improved growth, reduced adiposity and a lower risk of childhood overweight and obesity. Such patterns are characteristically high in fruit and vegetable consumption. These foods deliver an abundance of essential vitamins, minerals, dietary fibre and bioactive compounds with antioxidant and anti-inflammatory properties.

There is also a postnatal dimension. Maternal dietary habits often persist after childbirth and may influence a child’s developing food preferences and consumption patterns through mechanisms such as parental modelling and early exposure to a wide range of flavours.

What was already known, and what was missing

Previous studies examining maternal fruit and vegetable (FV) consumption during pregnancy have focused largely on birth weight and infant growth up to six months of age. Fruit juice consumption during pregnancy has been linked inconsistently to offspring adiposity or overweight, and earlier work did not distinguish between natural and commercial fruit juices.

To the authors’ knowledge, no prospective study had comprehensively examined maternal consumption of fruit and vegetables alongside different types of fruit juice in relation to childhood overweight and obesity. The current study set out to examine these associations in children up to four years of age.

Study characteristics

The researchers drew on data from the ECLIPSES trial, a community-based study conducted in Spain. All participants were healthy pregnant women aged at least 18 years, with a gestational age of 12 weeks or less at recruitment.

This observational analysis included 252 women from the trial who had provided dietary data via a food frequency questionnaire at 12, 24 and 36 weeks of pregnancy, together with information on the overweight or obesity status of their four-year-old children born from the index pregnancy.

Participants included in this analysis had higher educational attainment and were older than those who were not included. Within the sample, 24.6% of children were living with overweight or obesity.

Average maternal intakes were approximately 119 g/day for fruit and 74.5 g/day for vegetables. Fruit juice consumption averaged 105 g/day, with natural fruit juice accounting for 55% of that total.

Findings: fruit and vegetables

Greater maternal fruit and vegetable intake was inversely associated with overweight or obesity in the offspring when the highest tertile of intake was compared with the lowest. However, when fruit and vegetables were examined separately, neither showed an independent association with the children’s weight outcomes.

Findings: fruit juice

Neither total nor natural fruit juice consumption was associated with overweight or obesity in the offspring. Commercial fruit juice intake, by contrast, was linked with higher odds of these outcomes. The authors treated this as an exploratory finding, because multiple correlated dietary exposures and comparisons were evaluated.

It is important to note how the category was defined. “Commercial fruit juice” was a broad grouping that encompassed all commercially produced or packaged juices regardless of added sugar, including 100% packaged juice, juice from concentrate, nectars and fruit drinks. These subtypes were not analysed separately.

Sensitivity analyses produced broadly similar estimates to the primary results. None of the associations reached statistical significance when intake was modelled continuously in 100 g/day increments, and no evidence of departure from linearity was observed.

Biological pathways the authors propose

These findings add to a growing body of evidence suggesting that maternal diet in pregnancy may influence offspring health. The authors postulate that the rich antioxidant and anti-inflammatory content of fruit and vegetables, stemming from multiple bioactive compounds, may reduce oxidative stress and systemic inflammation while helping to regulate metabolic pathways.

The abundant dietary fibre in fruit and vegetables, coupled with their typically low glycaemic load, may also support glucose regulation during pregnancy. The authors are explicit that these mechanisms are biologically plausible but cannot be proved by the findings of the current study.

The role of family eating patterns after birth

Postnatal family eating patterns may also help explain the observed relationship. Relevant factors include a child’s exposure to fruit and vegetables in early childhood, the home food environment and parental example. Previous studies have reported higher fruit and vegetable intake in early childhood where maternal diet during pregnancy was of higher quality.

This hypothesis could not be tested in the present analysis, as the children’s dietary intake was not followed up and no information on the home food environment was available.

Why commercial juice may behave differently

The authors offer several possible explanations for the association between maternal commercial fruit juice consumption in pregnancy and overweight or obesity in childhood. A previous compositional analysis cited by the authors reported higher sucrose and total carbohydrate contents in commercially available juices than in natural juices. Prenatal exposure to sweet flavours may also influence the development of taste preferences for sweet foods after birth.

In addition, commercial fruit juice consumption during pregnancy might act as a marker of a broader family lifestyle pattern that affects a child’s risk of obesity. As with the proposed biological mechanisms, none of these hypotheses were tested in the study.

For practitioners working with families in this space, the interplay between prenatal nutrition, the early home food environment and later weight trajectories is precisely the territory covered by The College of Contemporary Health’s CPD short course Childhood Obesity Essentials, which supports clinicians in translating this kind of evidence into everyday practice.

Limitations

The observational nature of the study precludes causal inference. Residual confounding from maternal, family and postnatal infant or child factors also remains possible.

The results were not adjusted for gestational diabetes, paternal BMI, family socioeconomic status, or the child’s dietary and physical activity profile. Longitudinal data on the children’s dietary intake up to age four were unavailable.

A high rate of loss to follow-up from initial recruitment produced notable differences in maternal age and educational level between the initial and final samples, which may have introduced selection bias. Self-reported dietary intake is a further potential source of error.

The relatively small number of overweight and obesity cases increased the risk of statistical overfitting, and the multiple correlated dietary comparisons mean that chance findings cannot be ruled out, particularly in relation to commercial fruit juice.

Finally, the findings may not be generalisable to other populations.

Conclusion

The study found that higher maternal fruit and vegetable consumption was associated with lower odds of overweight and obesity in children at four years of age. An exploratory analysis further suggested that higher maternal consumption of commercial fruit juice was associated with higher odds of these outcomes.

Given the observational design, the study cannot establish causality and should not be taken as support for specific dietary interventions. Future research should follow up children within larger cohorts while adjusting for the wider range of maternal, family and child-related factors that could shape this association. The underlying pathways also remain to be elucidated.

CCH insight

Evidence on early-life determinants of weight is developing quickly, and the practical questions it raises – how to discuss nutrition in pregnancy, how to support families without stigma, and how to use people-first language with confidence – arrive in clinic long before the science is settled.

Childhood Obesity Essentials is a CPD short course from The College of Contemporary Health designed for healthcare professionals who support children, young people and their families. It offers a grounding in the contemporary evidence base and the communication skills needed to apply it sensitively.

Explore Childhood Obesity Essentials →

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