medication Tag

GLP-1 Receptor Agonists Show Potential to Reduce Mental Health Risks in People with Diabetes and Obesity

Key Takeaways: 

• GLP-1 receptor agonists were associated with a reduced risk of worsening mental illness in people living with diabetes and co-existing anxiety or depression
  
• Semaglutide and liraglutide showed the most notable effects, including reductions in depression, anxiety, and self-harm risk
  
• Findings from a large Swedish cohort study highlight potential dual benefits, though randomised trials are still needed
  
  
  

Growing interest in the mental health effects of GLP-1 therapies

A large national cohort study from Sweden, published in The Lancet Psychiatry, suggests that glucagon-like peptide-1 receptor agonists may offer benefits beyond metabolic control. The findings indicate that medications such as semaglutide and liraglutide could help reduce the risk of worsening mental illness in people living with diabetes and co-existing obesity, anxiety, or depression.

GLP-1 receptor agonists are widely used in the management of type 2 diabetes and obesity. However, their impact on mental health outcomes has remained uncertain, with previous research producing mixed results. This study contributes new large-scale evidence suggesting a potentially protective effect.

Mental illness and diabetes – a high-risk overlap

People living with diabetes are known to have a higher risk of mental health conditions, including depression, anxiety, and suicide. This overlap creates a complex clinical picture, where both metabolic and psychological factors influence outcomes.

The researchers emphasised that understanding how commonly prescribed antidiabetic medications affect mental health is essential, particularly in populations already at elevated psychiatric risk.

Study design and population

The study analysed data from Swedish national electronic health registers, covering the period from 2009 to 2022. Researchers identified individuals with diagnosed depression or anxiety who were also receiving antidiabetic treatment.

Participants who used GLP-1 receptor agonists were compared with those who did not use these medications, as well as with individuals taking other second-line antidiabetic therapies.

In total, nearly 95,500 people were included in the analysis. Approximately 60% of participants were female and 40% male, with a mean age of around 50 years. Data on ethnicity were not available.

During the follow-up period, almost 22,500 individuals used GLP-1 receptor agonists.

Outcomes measured

The study assessed several primary and secondary outcomes related to mental health.

Primary outcomes included:

• Psychiatric hospitalisation
• Sick leave exceeding 14 days due to psychiatric reasons
• Hospitalisation due to self-harm
• Death by suicide
  

Secondary outcomes included:

• Worsening symptoms of depression or anxiety
• Substance use disorder
• Self-harm
  

Reduced risk of worsening mental illness

The findings indicated that some GLP-1 receptor agonists were associated with a lower risk of worsening mental health outcomes.

Semaglutide and liraglutide were linked to a 42% and 18% lower risk of worsening mental illness, respectively, compared with people who did not use GLP-1 therapies.

When examining specific outcomes:

• Semaglutide was associated with a 44% lower risk of worsening depression
• A 38% reduced risk of worsening anxiety
• A 47% lower likelihood of worsening substance use disorder

Liraglutide showed a more limited effect, with a 26% reduction in the risk of worsening depression, but no significant impact on other mental health outcomes.

Other GLP-1 receptor agonists, including exenatide and dulaglutide, did not demonstrate meaningful changes in risk.

Impact on self-harm risk

One of the most notable findings was the association between GLP-1 receptor agonist use and a reduced risk of self-harm.

Overall, these medications were linked to a 44% lower risk of self-harm compared with non-use, suggesting a potentially important role in mitigating severe psychiatric outcomes in this population.

Implications for clinical practice

The results suggest that certain GLP-1 receptor agonists may provide dual therapeutic benefits for people living with diabetes and obesity, addressing both metabolic and mental health outcomes.

However, the authors cautioned that observational findings cannot establish causality. They highlighted the need for randomised controlled trials to confirm these associations and better understand the mechanisms involved.

Conclusion

This large Swedish cohort study provides evidence that some GLP-1 receptor agonists, particularly semaglutide and liraglutide, may be associated with reduced risks of worsening mental illness and self-harm in people living with diabetes and co-existing psychiatric conditions.

While further research is required, the findings point towards a potentially valuable role for these medications in addressing the interconnected challenges of metabolic and mental health.

CCH insight:

Yet more positive news about GLP-1 medications. This is very encouraging, particularly as there are so many drugs that have negative side-effects regarding mental health. However, this study only shows an association, and not causation, and did not adjust for the possible effects of losing weight – those on GLP-1 therapy may have experienced improved mood and mental health due to the fact they were losing weight, rather than as a direct effect of the drug. More research is needed to elucidate the complex interactions of obesity and mental health and the effects of GLP-1 medications.

Read More

Weight Loss Drugs May Be Linked to Bone Health Risks, Five-Year Study Shows

Key Takeaways:

• A large observational study suggests a modest increase in osteoporosis and related conditions among people taking GLP-1 receptor agonists over five years
  
• The underlying cause remains unclear, with weight loss itself, rather than the drugs alone, likely contributing to changes in bone health
  
• Despite these findings, the cardiovascular and metabolic benefits of GLP-1 therapies continue to outweigh potential skeletal risks for most people
  
  
  

Growing use of GLP-1 therapies raises new questions

Glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 drugs, are widely used to manage type 2 diabetes and support weight loss. These medications are recognised for their ability to reduce body weight, improve glycaemic control, and lower cardiovascular risk.

However, emerging long-term data are beginning to highlight potential concerns relating to bone health. A new study, presented at the 2026 annual meeting of the American Academy of Orthopaedic Surgeons, examined five years of real-world data and suggests that these treatments may be associated with an increased risk of certain skeletal conditions.

The findings are observational and have not yet undergone peer review. They demonstrate association rather than causation. Nevertheless, given the rapid uptake of GLP-1 receptor agonists, researchers emphasise the need for careful, ongoing evaluation.

Study findings – signals of increased skeletal risk

Researchers analysed medical records from more than 146,000 adults living with obesity and type 2 diabetes over a five-year period.

Among those taking GLP-1 therapies, approximately 4 percent developed osteoporosis, compared with just over 3 percent of those not taking these medications.

Additional findings included:

• Osteomalacia, or bone softening, occurred in around 0.2 percent of people using GLP-1 drugs, compared with 0.1 percent in the control group
  
• Gout was slightly more common, affecting 7.4 percent of people taking GLP-1 therapies compared with 6.6 percent in those not taking them
  

Lead researcher Muaaz Wajahath, a medical student at Michigan State University College of Human Medicine, highlighted the importance of emerging long-term data:

“We are just now reaching the precipice where five- and 10-year follow-up data are becoming available for patients taking GLP-1 medications,” Wajahath said. “Any medication that sees this rapid adoption warrants close examination, particularly in orthopedics, where obesity and surgical intervention often overlap.”

Dr Giles Scuderi, an orthopaedic surgeon and vice president of Northwell Orthopedics, commented on the findings:

“The study findings contradict recent assertions of musculoskeletal protection and suggest that GLP-1 RA exposure may confer increased long-term skeletal risk.”

Is the risk driven by the drug or by weight loss?

A key question remains whether the observed risks are directly caused by GLP-1 medications or are instead related to weight loss itself.

People living with obesity and type 2 diabetes already have elevated risks of inflammation and bone fragility. In addition, weight loss – particularly when rapid or substantial – can affect bone metabolism.

Dr James J. Chao explained:

“As with any weight loss, bone remodeling can occur if patients lose weight on these medications.”

Bone remodelling is the continuous process of breaking down old bone and replacing it with new tissue. During periods of calorie deficit, this balance can shift, resulting in net bone loss.

“If patients lose lean mass on these medications, bone health can be affected due to less strain being placed on bones,” he added.

Dr Fernando Ovalle Jr. reinforced that this is not unique to GLP-1 therapies:

“We’ve seen it with bariatric surgery for many years and even with aggressive caloric restriction. That’s not unique to GLP-1s.”

Balancing risks and benefits

Despite these findings, experts continue to support the use of GLP-1 receptor agonists in appropriate patients.

These medications have demonstrated strong benefits, including:

• Improved glycaemic control
• Reductions in blood pressure and lipid levels
• Lower risk of heart attack and stroke
  

“In high-risk patients, those benefits are substantial and often life-saving,” Ovalle said.

As a result, the overall benefit–risk balance remains favourable in most cases. While there may be a modest increase in fracture or gout risk, these risks can typically be monitored and managed.

Scuderi echoed this perspective:

“Since heart disease is a leading cause of death, the potential risk of muscle and bone problems might be less important.”

He also emphasised the importance of active clinical management rather than passive prescribing.

Practical steps to protect bone health

Healthcare professionals can take a proactive role in supporting people receiving GLP-1 therapies.

Recommended strategies include:

• Ensuring adequate protein intake to support muscle mass
• Maintaining sufficient calcium and vitamin D levels
• Engaging in regular resistance and weight-bearing exercise
• Avoiding excessively rapid or unsupported weight loss

“Strength training, in particular, is critical,” Ovalle said. “Preserving muscle mass protects bone. If a patient loses weight but also loses significant muscle, fracture risk can increase regardless of the medication used.”

Certain groups may require closer monitoring:

• Postmenopausal women
• Older adults
• Individuals with a history of fractures
  

Gout risk may also increase temporarily during periods of rapid weight loss.

“Regarding gout, rapid weight loss and changes in uric acid metabolism can transiently increase flares,” Ovalle said. “That’s something we’ve seen even outside of GLP-1 therapy.”

Building the nutritional knowledge to guide patients through these supportive measures – adequate protein, key micronutrients and protecting lean mass during weight loss – is the focus of professional training such as the College of Contemporary Health’s Nutrition & Weight Management Essentials, a CPD-accredited online short course.

For individuals concerned about bone health, targeted supplementation may be considered. Scuderi noted that healthcare professionals may recommend therapeutic doses of dietary supplements to support lean mass retention and reduce inflammation.

A signal worth monitoring, not a cause for alarm

While early long-term data suggest a potential association between GLP-1 therapies and bone-related risks, these findings should be interpreted with caution.

The study does not establish causation, and multiple factors – including weight loss, underlying conditions, and changes in body composition – are likely to contribute.

At present, GLP-1 receptor agonists remain a valuable and often transformative option for people living with obesity and type 2 diabetes, provided their use is accompanied by appropriate clinical oversight and supportive lifestyle measures.

CCH insight

With so many people taking GLP-1 medications, it is important to keep researching the long-term effects, and this study sheds important light on potential risks with regard to bone health. The most important message here, however, is that this reminds us how it is vital that patients on GLP-1 therapy need to be carefully monitored and supported, particularly during the first year or so when weight loss is relatively rapid. If bone health is affected, this can be managed and treated. If bone health is affected, this can be managed and treated. Much of that support is nutritional: CCH’s Nutrition & Weight Management Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) gives healthcare professionals a solid grounding in nutrition and weight management, including how to help patients meet their protein, calcium and vitamin D needs and preserve lean muscle during periods of rapid weight loss.

Explore Nutrition & Weight Management Essentials →

Source: The Epoch Times  

Read More

Gut Microbiome May Shape Responses to GLP-1 Therapies in Obesity and Type 2 Diabetes

Key Takeaways: 

• The gut microbiome may contribute to why people respond differently to GLP-1 receptor agonists, although causality remains unproven
  
• GLP-1 therapies and associated weight loss can alter gut microbial composition, but findings are inconsistent
  
• Dietary and behavioural changes during treatment are likely key drivers of microbiome shifts rather than direct drug effects
  
  
  

Emerging link between the gut microbiome and GLP-1 treatment response

A recent review published in the Canadian Journal of Physiology and Pharmacology highlights growing interest in the role of the gut microbiota in shaping responses to glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 RAs. These medications are widely used in the management of people living with type 2 diabetes and those living with overweight or obesity.

The analysis suggests that gut microbial communities and their metabolites may contribute to the variability observed in treatment responses. At the same time, GLP-1 receptor agonists may themselves influence the composition of the gut microbiota. This bidirectional relationship positions the microbiome as both a potential contributor to treatment variability and a possible future target for more personalised metabolic therapies.

The gut microbiome as a regulator of metabolic health

There is increasing evidence that gut microbes play an active role in metabolic regulation. Preclinical studies using faecal microbiota transplantation have demonstrated that microbial communities can transfer traits such as glucose regulation and body mass. However, findings in human studies have been less consistent.

Despite the widespread use of GLP-1 receptor agonists, research exploring their interaction with the human gut microbiome remains limited. This is particularly notable given the considerable variation in how individuals respond to these treatments. Differences in microbial composition may partly explain this variability, although a definitive causal relationship has not yet been established.

In the review, researchers examined potential interactions between GLP-1 therapies, diet, gastrointestinal symptoms, body weight, and gut microbial composition.

Interactions between GLP-1 signalling and gut microbes

GLP-1 is a naturally occurring hormone that regulates appetite and blood glucose levels by binding to the GLP-1 receptor. It is released by L-cells in the intestine following nutrient intake. Because this release occurs in the lower intestine, GLP-1 operates in close proximity to the gut microbiota, raising the possibility of direct interaction.

Microbial metabolites such as bile acid derivatives and short-chain fatty acids can influence endogenous GLP-1 secretion and activity. These findings suggest that gut microbes may play a role in modulating GLP-1 signalling pathways. However, direct evidence demonstrating that microbial composition determines treatment response to GLP-1 receptor agonists in humans remains limited.

GLP-1 therapies may also indirectly affect the microbiome through changes in appetite, gastrointestinal motility, and dietary intake.

Clinical effectiveness of GLP-1 receptor agonists and variability in response

GLP-1-based therapies including liraglutide, semaglutide, and tirzepatide are now well established in the treatment of type 2 diabetes and obesity. Clinical trials have demonstrated significant weight loss outcomes:

• Tirzepatide – approximately 11.9–17.8% greater weight loss than placebo over 72 weeks
  
• Semaglutide – approximately 12.4% greater weight loss over 68 weeks
  
• Liraglutide – approximately 8.0% weight reduction compared with placebo over 56 weeks
  

Despite these results, individual responses vary widely. Differences in the gut microbiome have been proposed as one potential contributing factor, although this remains an area of ongoing investigation.

Microbiome changes associated with GLP-1 therapies

GLP-1 receptor agonists may influence gut microbial composition in people living with type 2 diabetes and obesity. Historically, obesity has been associated with a higher Firmicutes-to-Bacteroidetes ratio. Some studies suggest that weight loss is linked to increased microbial diversity and a greater abundance of beneficial genera such as Akkermansia.

Clinical observations include:

• Increased Akkermansia levels after six weeks of liraglutide therapy
  
• Increased levels of Bacteroidota, Actinobacteriota, and Proteobacteria following 12 weeks of semaglutide
  
• A reduction in Firmicutes in some cohorts
  

However, these findings are based on a limited number of heterogeneous studies. Many have involved people living with type 2 diabetes who were also taking other medications such as metformin, which is known to independently influence the gut microbiome.

GLP-1 receptor agonists, when combined with lifestyle modification, can lead to approximately 8–20% body weight reduction over several months to one year. Nevertheless, reported microbiome changes remain inconsistent. Some studies show increased diversity, while others report minimal or no significant changes.

Dietary changes during treatment and their microbiome impact

Evidence suggests that observed microbiome shifts may largely reflect downstream effects of weight loss and metabolic improvement rather than direct drug–microbiome interactions.

GLP-1 therapies are associated with changes in eating behaviour, including reduced appetite, increased satiety, and altered taste perception. People using these medications often improve their dietary patterns, with reduced consumption of refined grains, processed foods, beef, and sugar-sweetened beverages. Caloric intake may decrease by approximately 16–39%.

In 2025, organisations including The Obesity Society, American College of Lifestyle Medicine, American Society for Nutrition, and Obesity Medicine Association issued clinical guidance emphasising the importance of nutritional assessment and management of gastrointestinal side effects during GLP-1 therapy.

This guidance recommends prioritising nutrient-dense foods such as vegetables, fruits, whole grains, lean proteins, seeds, and nuts, while limiting refined carbohydrates, sugar-sweetened beverages, red and processed meats, fast foods, and highly processed snacks. Given the strong influence of diet on gut microbial composition, these dietary changes are likely to play a significant role in shaping the microbiome during treatment.

Future directions and research priorities

The review concludes that current evidence points towards behavioural and dietary changes, alongside weight loss, as the primary drivers of microbiome alterations observed during GLP-1 receptor agonist therapy.

However, the gut microbiome remains a promising area for future research. Microbiome profiling could eventually help predict treatment response more accurately in people living with obesity and type 2 diabetes.

Future studies should include:

• Larger and more diverse populations
  
• Longitudinal monitoring of microbiome changes
  
• Inclusion of people living with obesity who do not have diabetes
  
• Detailed tracking of dietary intake, gastrointestinal symptoms, and treatment adherence
  

Emerging therapies such as oral GLP-1 receptor agonists and new agents like orforglipron may offer further insight into direct interactions between medications and gut microbes, particularly as orally administered drugs come into direct contact with the gastrointestinal tract.

Understanding these relationships may ultimately support more personalised and effective approaches to obesity and diabetes care.

Read More

Semaglutide and Bimagrumab Combination Shows Greater Weight Loss While Preserving Muscle Mass

Key Takeaways: 

• A phase 2 clinical trial found that combining semaglutide with the antibody bimagrumab produced greater overall weight loss while largely preserving lean body mass.
  
• Participants receiving the two-drug combination lost 22.1% of body weight on average, with over 90% of the reduction coming from fat mass.
  
• The findings highlight the importance of focusing on body composition rather than weight alone when evaluating treatments for people living with obesity.
  
  
  

Combining two mechanisms to improve obesity treatment

A recent clinical trial has found that combining the GLP-1 receptor agonist semaglutide with bimagrumab, an antibody that blocks activin signalling pathways, may produce greater weight loss while preserving lean body mass.

The findings were reported in the paper “Bimagrumab and semaglutide alone or in combination for the treatment of obesity: a phase 2 randomized clinical trial”, published in the journal Nature Medicine. The study describes the results of the BELIEVE trial, led by Dr Steven Heymsfield of the Pennington Biomedical Research Center.

GLP-1–based therapies have become highly effective tools for reducing body weight in people living with obesity. However, a recognised limitation of these therapies is that up to 40% of the weight lost may come from lean mass, which includes skeletal muscle and connective tissue.

The BELIEVE trial explored whether combining semaglutide with bimagrumab could address this issue by enhancing fat loss while protecting lean body mass.

Why lean mass preservation matters

Historically, obesity treatment has often focused on reductions in body weight as the primary outcome. However, researchers increasingly emphasise the importance of preserving muscle mass, which plays a vital role in both physical function and metabolic health.

Dr Heymsfield explained that maintaining lean mass could be particularly important for people living with obesity who may already be at risk of low muscle mass.

“Obesity treatment has traditionally focused on the number on a scale. Patients with obesity who are at risk for low muscle mass, affecting both physical and metabolic function, may benefit from treatments that maximize fat mass reduction while preserving skeletal muscle,” said Heymsfield, who is an LSU Boyd Professor and director of the Metabolism and Body Composition Laboratory.

He also highlighted the complementary biological mechanisms of the two drugs.

“Bimagrumab and semaglutide work through distinct biological pathways, and when combined, we observed not only a preservation of lean mass but also an additive reduction in fat mass that exceeded what either therapy achieved alone.”

Design of the BELIEVE phase 2 trial

The BELIEVE study was designed as a double-blind, placebo-controlled clinical trial evaluating the effects of semaglutide and bimagrumab used either alone or in combination.

Participants were randomly assigned to several treatment groups:

• Bimagrumab only
  
• Semaglutide only
  
• Combination therapy
  

Each medication was also administered at two different dosing levels:

• Bimagrumab: 10 mg/kg or 30 mg/kg
  
• Semaglutide: 1.0 mg or 2.4 mg
  

Because of these dosing combinations, the trial ultimately included nine randomised groups.

Bimagrumab was administered every 12 weeks, while semaglutide was given once weekly. Participants were followed over a 72-week treatment period.

Weight loss and body composition outcomes

The results showed clear differences between the treatment groups in terms of both total weight loss and the composition of that weight loss.

Participants receiving bimagrumab alone experienced an average weight reduction of 10.8%. Notably, all of this reduction was attributable to fat mass, while lean mass increased by 2.5%.

Those treated with semaglutide alone lost an average of 15.7% of body weight, with 71.8% of the weight loss coming from fat mass.

The most striking results were seen in participants receiving the combination therapy. These individuals experienced an average weight loss of 22.1%, with 92.8% of the weight reduction attributable to fat mass, while lean mass was largely preserved.

These findings suggest that the combination therapy may offer a way to achieve substantial reductions in body weight while maintaining the muscle mass that supports metabolic health and physical function.

Improvements in metabolic and inflammatory markers

Beyond weight loss and body composition, the study also identified several favourable metabolic changes.

Participants experienced up to an 83% reduction in high-sensitivity C-reactive protein (hsCRP), an inflammatory marker that is associated with increased cardiovascular risk.

The study also reported a substantial increase in adiponectin, a hormone that plays an important role in:

• Improving insulin sensitivity
  
• Supporting fat metabolism
  
• Promoting anti-inflammatory processes
  

Among participants who had indicators of prediabetes at baseline, some of the groups receiving the two-drug combination experienced complete reversion to normoglycaemia, meaning all participants in those groups moved from a prediabetic state to normal blood glucose levels.

Safety and tolerability

Overall, the drug combination was generally well tolerated by participants. Reported side effects were broadly consistent with the known safety profiles of the individual drugs.

However, researchers noted that participants receiving bimagrumab experienced some common adverse events, including:

• Mild-to-moderate acne
  
• Muscle spasms
  

The study authors emphasised the need for continued clinical development and further investigation to better understand these effects.

Moving beyond the number on the scale

The BELIEVE trial also underscores a broader shift in how obesity treatments may be evaluated in the future.

Rather than focusing solely on weight or body mass index, researchers increasingly argue that body composition measures, such as the proportion of fat mass and lean mass, provide more meaningful insight into treatment effectiveness and overall health outcomes for people living with obesity.

Keeping pace with how GLP-1 therapies work and how to weigh emerging trial evidence like this is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course.

Funding and study oversight

The study was funded by Eli Lilly and Company. The trial was originally designed by Versanis Bio, a wholly owned subsidiary of Eli Lilly.

Versanis Bio oversaw the clinical trial and provided partial funding before its acquisition by Lilly.

CCH insight:

The results for bimagrumab are very exciting. Although overall weight loss was less for bimagrumab than semaglutide, the amount of fat lost was very similar, but with retention or even increase of muscle mass. As muscle is an important metabolic tissue, you can argue that in this case the lesser weight loss is a better outcome than the higher weight loss, because the weight that is retained is muscle, not fat because the weight that is retained is muscle, not fat. Making sense of fast-moving evidence like this – and the mechanisms behind it – is exactly what CCH’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work CPD short course (2 CPD hours, fully online, CPD-accredited) is built to support, giving healthcare professionals a clear grounding in how these medications work and how to appraise the evidence with confidence, whether or not they prescribe.

Explore GLP-1RAs in Focus →

Read More

GLP-1 Weight-Loss Drugs Found to Work in Rare Genetic Obesity

Key Takeaways:

• GLP-1–based medicines reduced body weight and improved metabolic health in animals lacking the MC4R receptor, a critical regulator of appetite and body weight
  
• The findings suggest these therapies may work through alternative brain and peripheral pathways, offering potential treatment options for people living with rare genetic obesity
  
• Researchers highlight potential risks linked to lean mass loss, emphasising the importance of long-term monitoring and muscle-preserving treatment strategies
  
  
  

Understanding genetic obesity and loss of appetite control

For individuals born with certain genetic mutations affecting appetite regulation, managing body weight can resemble attempting to stop a vehicle with failing brakes. Despite sustained effort, biological signals governing hunger and energy balance do not respond normally.

One of the most important regulators of food intake is the melanocortin-4 receptor (MC4R), located within the hypothalamus. This receptor plays a central role in maintaining energy balance by responding to hormonal signals that indicate satiety.

When mutations disrupt signalling pathways linked to MC4R, individuals may experience profound dysregulation of appetite. Children affected by these mutations frequently develop severe early-onset obesity, and by adulthood many conventional interventions have produced limited or no sustained benefit.

New research published in the International Journal of Obesity now suggests that widely used GLP-1–based anti-obesity medicines may offer a potential therapeutic approach even when this critical biological pathway is absent.

Testing GLP-1 medicines without MC4R function

The research team investigated whether modern incretin-based therapies could still produce weight-loss effects in the complete absence of MC4R signalling.

To explore this question, scientists used genetically engineered mice lacking the MC4R gene entirely. These animals closely replicate clinical features seen in people living with MC4R pathway deficiency, including:

• Excessive food intake
  
• Rapid fat accumulation
  
• Fatty liver disease
  
• Elevated cholesterol levels
  
• Early insulin resistance
  

Under normal physiological conditions, hunger regulation relies heavily on signalling cascades such as the POMC–MC4R and leptin–MC4R pathways, which transmit satiety signals as the stomach approaches fullness. Disruption anywhere along these pathways can lead to some of the most treatment-resistant forms of obesity recognised in clinical medicine.

The researchers therefore posed a direct question: would GLP-1 therapies still work if MC4R signalling were completely removed?

Three leading anti-obesity drugs evaluated

The study examined three prominent weight-management medicines:

• Semaglutide
  
• Tirzepatide
  
• Retatrutide
  

All belong to the broader class of GLP-1–based therapies, which act on receptors distributed across the brain, pancreas and vagus nerve connecting the brainstem to abdominal organs.

Each drug was administered once daily via injection over a 21-day period.

Despite the absence of functional MC4R signalling, all three treatments produced substantial anti-obesity effects. As the authors reported:

“Our findings demonstrate that all three GLP-1 analogs exhibit significant anti-obesity effects in MC4R KO mice.”

Significant weight and metabolic improvements

Weight reduction occurred across all treatment groups:

• Semaglutide reduced body weight by an average of 19.7 percent
  
• Retatrutide achieved a 24.1 percent reduction
  
• Tirzepatide, which targets both GLP-1 and GIP receptors, produced the largest effect with a 31.6 percent reduction
  

Importantly, these outcomes occurred in animals completely lacking MC4R function.

Food intake declined consistently across groups, accompanied by broader metabolic improvements. Researchers observed:

• Reduced liver injury markers
  
• Lower cholesterol and triglyceride levels
  
• Suppression of liver genes associated with fat production
  

The authors concluded:

“These results suggest that GLP-1 analogs may provide an effective treatment option for patients with MC4R-POMC pathway deficiencies.”

Alternative brain and peripheral mechanisms

The findings indicate that GLP-1 therapies may bypass defective MC4R signalling entirely.

According to the research team:

“GLP-1 analogs appear to exert their anti-obesity effects through central pathways that do not involve MC4R, as well as via peripheral mechanisms involving the vagus nerve.”

This alternative mechanism may explain why the drugs remained effective despite removal of a pathway traditionally considered essential for appetite regulation.

Tirzepatide’s superior performance may relate to its additional action on the GIP receptor, providing dual hormonal signalling that enhances metabolic effects.

Implications for rare genetic obesity disorders

The results carry particular relevance for clinicians caring for people living with rare genetic obesity conditions, including POMC deficiency and Prader–Willi syndrome.

Currently, one approved therapy for some of these disorders, setmelanotide, works by stimulating the melanocortin pathway itself. However, treatment effectiveness depends on partial pathway function, which may limit outcomes in individuals with more severe deficiencies.

GLP-1–based therapies differ in that their effects do not appear dependent on MC4R signalling, potentially expanding treatment possibilities for individuals previously considered difficult to treat pharmacologically.

Lean mass loss and long-term considerations

Alongside reductions in fat mass, researchers observed decreases in lean body mass across all treatment groups. This raises important clinical considerations regarding prolonged therapy.

The authors cautioned:

“Chronic suppression of food intake could lead to muscle loss, potentially resulting in sarcopenia.”

They further noted that:

“Combination strategies, possibly including agents that preserve or increase muscle mass, may help mitigate this effect.”

These findings reinforce growing clinical discussion around muscle preservation during pharmacological weight management.

Early evidence, not yet clinical practice

While the results are encouraging, important limitations remain.

The study:

• Ran for only three weeks
  
• Included only male mice
  
• Lost two animals from the tirzepatide group before completion
  
• Has not yet been replicated in human clinical trials involving individuals with MC4R mutations
  

As such, the findings represent proof of biological concept rather than immediate clinical guidance.

The researchers summarised their conclusion clearly:

“This study provides the first demonstration that GLP-1 analogs can be effective in treating obesity associated with MC4R deficiency.”

A potential shift in understanding obesity treatment

The study contributes to a broader shift in obesity science, suggesting that effective treatment may not depend on restoring a single disrupted pathway. Instead, therapies capable of engaging multiple neural and peripheral systems may overcome even profound genetic drivers of obesity.

For people living with rare genetic forms of obesity, these findings offer cautious optimism that future treatments may succeed where traditional approaches have historically fallen short.

Read More

Mice Study Suggests Tirzepatide Enhances Metabolism by Activating Brown Fat in Addition to Reducing Weight

Key Takeaways: 

• A preclinical mouse study indicates that tirzepatide may improve metabolism not only by reducing appetite, but also by activating brown adipose tissue.
  
• The research suggests that this activation increases energy expenditure and supports improvements in blood glucose and lipid levels.
  
• Findings remain preliminary and require confirmation in human studies before clinical conclusions can be drawn.
  
  
  

A closer look at tirzepatide’s metabolic effects

Tirzepatide has transformed the treatment landscape for people living with obesity and for those with poorly controlled type 2 diabetes mellitus. Despite its established clinical benefits, the precise molecular and cellular mechanisms underpinning its effects are not yet fully understood.

A recent study conducted in mice provides new insight into how the drug may influence metabolism beyond its well-recognised impact on body weight. The findings suggest that tirzepatide directly activates brown adipose tissue, a specialised form of fat involved in energy expenditure. According to the researchers, this discovery helps clarify how the drug works and may inform the development of more comprehensive treatments for obesity and related metabolic diseases.

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

A dual-action therapy

Tirzepatide, marketed under the name Mounjaro, is approved for weight management in adults living with obesity or with overweight accompanied by comorbidities. It is also indicated for the treatment of inadequately controlled type 2 diabetes.

Unlike earlier anti-obesity medicines, tirzepatide acts simultaneously on two hormonal receptors – glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This dual mechanism leads to substantial reductions in body weight, primarily through decreased food intake driven by appetite suppression.

However, appetite reduction alone may not explain the full spectrum of its metabolic effects.

Investigating effects on adipose tissue

To better understand how tirzepatide exerts its actions, researchers conducted a detailed analysis of its effects on different fat depots in an experimental mouse model. Such in-depth tissue analysis is not feasible in humans.

In the study, mice were rendered obese through a high-fat diet and then treated with tirzepatide. Their outcomes were compared with a control group of mice that consumed the same quantity of food but did not receive the drug. This design allowed the researchers to distinguish between effects caused directly by the drug and those resulting solely from reduced caloric intake.

The analysis revealed that tirzepatide activates brown adipose tissue. Unlike white adipose tissue, which primarily stores excess energy and accumulates in obesity, brown adipose tissue specialises in burning calories to generate heat.

“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.

Metabolic benefits beyond appetite suppression

The activation of brown adipose tissue is particularly significant because it indicates that tirzepatide may exert metabolic benefits independent of weight loss due to appetite reduction.

“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.

By enhancing the body’s ability to utilise both glucose and lipids, activation of brown fat may contribute to improved glycaemic control and lipid profiles in addition to weight reduction.

Implications for obesity treatment strategies

For several years, activation of brown adipose tissue has been viewed as a promising strategy for tackling obesity and metabolic disorders. However, previous pharmacological attempts to stimulate brown fat have frequently been limited by adverse effects, particularly cardiovascular complications.

“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.

These findings support the broader principle that obesity treatments may be more effective when they target multiple physiological pathways simultaneously. Addressing both energy intake and energy expenditure could offer a more comprehensive approach to weight management and metabolic health.

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

Towards more personalised prescribing

A deeper understanding of tirzepatide’s mechanisms may also influence how such medicines 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 personalized medicine, based not only on appetite or weight control, but also on overall metabolic status,” she emphasizes.

Such an approach could support more tailored treatment strategies for people living with obesity and metabolic disease, taking into account differences in metabolic function rather than focusing solely on body weight.

The need for caution and further research

Despite the promising findings, the researchers emphasise that the results are based on animal data and cannot yet be directly translated into clinical practice.

“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.

Further human studies will be required to confirm whether the activation of brown adipose tissue observed in mice also occurs in people receiving tirzepatide and whether it meaningfully contributes to its metabolic benefits.

Read More

GPs Offered £3,000 Incentive to Increase Prescribing of NHS Weight Loss Injections

Key Takeaways:

• GP practices in England will be eligible for a £3,000 annual payment for prescribing the maximum number of eligible patients the weight loss drug Mounjaro.
  
• Access to NHS weight loss injections remains tightly restricted, with eligibility based on BMI and specific health conditions.
  
• Professional bodies stress that prescribing decisions are driven by clinical judgement, not financial incentives, and warn that workload pressures may increase.
  
  
  

New financial incentives added to GP contract

GP practices across England are set to receive annual incentive payments of £3,000 for prescribing weight loss medication to the maximum number of patients who meet NHS eligibility criteria.

The payments will be incorporated into the national GP contract from April. In addition, practices will be able to receive approximately £1,000 per year for referring patients to weight loss support programmes.

Ministers have said the objective is to ensure that people who could benefit from structured weight management and pharmacological support are able to access it within primary care.

However, specialists in obesity care have cautioned that the overall impact of the scheme may be modest. They note that eligibility for NHS weight loss injections remains tightly restricted and that the incentive does not expand access to a broader population.

Focus on Mounjaro within primary care

The new incentive applies solely to Mounjaro, a next-generation injectable treatment for weight management.

Mounjaro became available on the NHS in 2025. Despite this, prescribing rates in general practice have reportedly been lower than expected, with some variation in uptake across different areas.

Another injectable weight loss medication, Wegovy, is also available through the NHS. However, it is not prescribed by GPs and is instead provided through specialist NHS weight management services.

More than one million people are estimated to be using weight loss injections in the UK. The majority, around nine in ten, are paying privately rather than receiving the medication through the NHS.

Government position: access based on need

The Health Secretary, Wes Streeting, described the medicines as potentially transformative for people living with obesity.

He said: “Weight loss drugs can be a real game changer for those who need them. I’m determined that access should be based on need, not ability to pay.

“Outside the NHS, we’ve seen those who can spare the cash buying privately, and the proliferation of rogue prescribers peddling dangerous unlicensed drugs that are putting patients at risk.

“Investing in general practice will help bring this modern medicine to the many, not just the few, and help shift the focus of the NHS from treatment to prevention.“

The government argues that embedding prescribing targets within the GP contract is consistent with longstanding practice. Incentive payments have previously been used to improve dementia diagnosis rates, increase vaccination uptake, and encourage the prescription of statins to reduce cardiovascular risk.

This marks the first time that weight loss injections have been formally included in the GP contract framework, with the £3,000 payment linked to prescribing the maximum number of eligible patients Mounjaro.

Strict eligibility criteria remain in place

Although the incentive has been introduced, NHS access to Mounjaro remains limited.

During the current financial year, GPs have only been permitted to prescribe the medication to people with severe obesity defined as a body mass index over 40, alongside certain weight-related health conditions.

From next year, eligibility is expected to expand to include people with a BMI over 35. By 2028, it is anticipated that 220,000 patients will be receiving Mounjaro through the NHS. Lower BMI thresholds apply for some ethnic groups.

Despite these planned expansions, the roll-out to date has been described as uneven, with variation between practices and regions.

Support from obesity advocates – with caveats

Katharine Jenner, Director of the Obesity Health Alliance, welcomed the move but emphasised its limitations.

She said: “This doesn’t mean weight loss drugs will suddenly be available to everyone who wants them.

“NHS access will remain very limited and focused on those with the greatest clinical need, and these treatments are most effective when combined with sustained support.“

She also stressed the importance of prevention alongside treatment:

“If we’re serious about moving from sickness to prevention, expanded treatment must go alongside stronger action to improve the food environment and prevent obesity in the first place.“

Her comments reflect a broader concern within public health that medication alone cannot address the structural drivers of obesity.

Concerns about equity and workload

Dr Katie Bramall, representing the British Medical Association, questioned whether the scheme would meaningfully reduce inequalities in access.

She said: “While the headlines promise much, in reality there will be no change to NHS England’s eligibility criteria for patients to access injectable weight-loss medication on the NHS.

“These proposals will do nothing over the next year to address the divide between those able to pay and those left waiting unable to afford private self-funded treatments“

Similarly, Professor Victoria Tzortziou Brown of the Royal College of GPs emphasised that prescribing decisions are rooted in clinical appropriateness rather than financial drivers.

She said: “GPs do not withhold treatment or prescribe based on financial incentives. Decisions are guided by clinical judgement and what is safest and most appropriate for individual patients.

“Widening the roll-out of these medications in general practice could end up increasing workload in a way that may not be sustainable and risk raising unrealistic expectations among patients who may not be eligible or for whom these medicines are not suitable.“

Supporting GPs to prescribe these medications safely and confidently – from patient selection through initiation, titration and managing side effects – is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Practice: Prescribing, a CPD-accredited online short course.

Her comments highlight the tension between expanding pharmacological options in primary care and managing existing workforce pressures.

A cautious step in a tightly controlled rollout

The introduction of incentive payments signals the government’s intention to embed weight loss pharmacotherapy more firmly within general practice. However, strict eligibility criteria remain in place and access is expected to expand gradually over several years.

While the policy aims to increase NHS provision and reduce reliance on private prescribing, professional bodies and advocacy groups have made clear that the immediate effect will be limited. For now, access continues to be targeted at people with the greatest clinical need, with broader prevention strategies still viewed as essential to addressing obesity at population level.

CCH insight:

It is surprising that GPs need incentivising to prescribe GLP-1 medications like Mounjaro – there is undoubtedly a huge need and demand for these drugs. The reluctance to prescribe them is most likely due to the weight bias that still pervades our society and our health system, the view that people shouldn’t need medication to manage their weight. Referring to these drugs as ‘weight loss jabs’ is not helpful – they are anti-obesity medications. Rather than offer a £3k bonus, GPs should be offered training in understanding obesity as a chronic, relapsing disease, and how GLP-1 medications not only support weight loss but can also improve long-term metabolic and cardiovascular health, and in the long run will save billions of pounds by reducing diabetes and heart disease by reducing diabetes and heart disease. That is precisely why targeted education matters more than a bonus: CCH’s GLP-1RAs in Practice: Prescribing CPD short course (2 CPD hours, fully online, CPD-accredited) equips prescribers with everything they need to use these medications well – from patient selection and initiation to titration, side-effect management and the wider conversation about obesity as a chronic disease.

Explore GLP-1RAs in Practice: Prescribing →

Read More

Tirzepatide Not Linked to Increased Depression or Suicidal Ideation in Obesity Trials

Key Takeaways: 

• A post hoc analysis of three SURMOUNT trials found no evidence that tirzepatide increases the risk of depression compared with placebo over 72 weeks.
  
• Rates of suicidal ideation and behaviour were low and similar between tirzepatide and placebo groups, with most reports assessed as low risk.
  
• Experts emphasise the need for routine mental health assessment in people living with obesity, alongside further research in populations with established psychiatric conditions.
  
  
  

Overview of the analysis

Once-weekly subcutaneous tirzepatide was not associated with an increased risk of depression compared with placebo, according to a post hoc analysis of the SURMOUNT clinical trial programme. The findings were published in Obesity and add to the growing body of evidence examining the psychiatric safety of incretin-based therapies used for weight management.

As previously reported by Healio, in January the Food and Drug Administration requested the removal of warnings related to suicidal ideation and behaviours from the labels of several obesity medications, including liraglutide 3 mg (Saxenda), semaglutide 2.4 mg (Wegovy) and tirzepatide (Zepbound).

In the newly published analysis, researchers reported that adults receiving tirzepatide across three SURMOUNT trials did not experience worsening of depression over the course of the studies.

“The low occurrence of these events with tirzepatide is similar to that observed in pooled analyses of semaglutide 2.4 mg and liraglutide 3 mg, both GLP-1 receptor agonists approved for weight management,” said Thomas A. Wadden, PhD, professor of psychology in psychiatry at the Perelman School of Medicine, University of Pennsylvania, in comments to Healio. “The present report provides the first detailed analysis of the risk of these psychiatric events with tirzepatide.”

Study design and assessment methods

The analysis included data from the SURMOUNT-1, SURMOUNT-2 and SURMOUNT-3 studies. Across all three trials, adults living with obesity or with overweight and at least one weight-related comorbidity were randomly assigned to receive once-weekly subcutaneous tirzepatide or placebo for 72 weeks.

Depression symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). Suicidal ideation and behaviour were assessed using the Columbia-Suicide Severity Rating Scale. In addition, investigators recorded neuropsychiatric adverse events during scheduled study visits.

Depression symptoms over time

A total of 4,056 adults were included in the pooled analysis, of whom 63 percent were women and 74 percent were White. Overall, 2,806 participants received tirzepatide and 1,250 received placebo. At baseline, mean PHQ-9 scores were 2.7 in the tirzepatide group and 2.6 in the placebo group, indicating minimal or no depressive symptoms.

By week 72, participants receiving tirzepatide experienced a 0.6-point greater reduction in PHQ-9 score compared with those receiving placebo.

Among participants who had no or minimal depression symptoms at baseline and received tirzepatide, 79.4 percent remained in that category through the end of safety follow-up. During follow-up, 17 percent reported mild symptoms, 2.9 percent reported moderate symptoms, 0.7 percent reported moderately severe symptoms and 0.1 percent reported severe symptoms.

A smaller proportion of participants in the tirzepatide group moved to a more severe depression category compared with the placebo group, 18.2 percent versus 24.3 percent respectively, with this difference reaching statistical significance (P < .001). Conversely, a higher proportion of those receiving tirzepatide moved to a less severe depression category compared with placebo, 52.4 percent versus 41.8 percent (P < .001).

Suicidal ideation and behaviour

At baseline, a history of suicidal ideation or behaviour was reported by 70 participants receiving tirzepatide and 38 participants receiving placebo. Through the end of safety follow-up, 0.6 percent of participants in both the tirzepatide and placebo groups reported suicidal ideation. Most of these events were classified as low risk.

Moderate-risk suicidal ideation was reported by 0.3 percent of participants receiving tirzepatide and 0.1 percent of those receiving placebo. High-risk suicidal ideation occurred in three participants receiving tirzepatide and one participant receiving placebo.

Suicidal behaviour was reported by two participants in the tirzepatide group and by none in the placebo group.

Treatment-emergent nervous system disorder adverse events occurred in 15.8 percent of participants receiving tirzepatide and 13 percent of those receiving placebo. The investigators reported no difference between groups in the occurrence of treatment-emergent psychiatric disorders overall.

Implications for mental health care in obesity

Wadden noted that he and his colleagues supported the FDA decision to remove warnings related to suicidal ideation and behaviour from the labels of incretin-based obesity medications. However, he stressed that mental health assessment remains essential in the care of people living with obesity.

“Persons with obesity, particularly with a BMI of more than 40 kg/m2, are at substantially increased risk of major depression and anxiety disorders,” Wadden said. “It’s critical that they receive the same mental health care that persons of average weight would when presenting with these conditions.”

He also highlighted the need for further research to better understand the effects of incretin-based therapies in people with established psychiatric conditions.

“Randomized trials of the GLP-1 obesity medications largely excluded persons who, in the past 2 years, had experienced major depression, schizophrenia or bipolar disorder, or who had a lifetime history of suicide attempt,” Wadden said. “GLP-1 medications potentially could be beneficial to individuals who suffer from these conditions. Small, carefully controlled studies would appear warranted, as would a close examination of the FDA’s recent retrospective cohort study of more than 2 million individuals. The FDA’s dataset likely included a far greater range of psychiatric status than found in the randomized controlled trials that evaluated tirzepatide and semaglutide for chronic weight management.”

Disclosures

Wadden reports advising for Novo Nordisk and WW and receiving grants on behalf of the University of Pennsylvania from Eli Lilly, Epitomee Medical and Novo Nordisk. All other relevant financial disclosures are reported in the study.

Read More

Nutrition Gaps Raise Safety Concerns as Use of GLP-1 Weight Loss Drugs Accelerates

Key Takeaways:

• Many people prescribed GLP-1 weight loss medications receive little or no structured nutritional guidance, increasing the risk of preventable vitamin and mineral deficiencies and loss of muscle mass.
  
• New research highlights a lack of high-quality evidence on how diet quality, protein intake, and micronutrient intake are affected during treatment with drugs such as semaglutide and tirzepatide.
  
• Experts warn that without integrated nutritional care, the rapid expansion of GLP-1 drug use could undermine long-term health benefits despite effective weight loss.
  
  
  

Experts from University College London and the University of Cambridge are warning that many people prescribed newer weight loss medications may not be receiving sufficient nutritional guidance to support safe and sustainable weight loss. As a result, some individuals may face avoidable risks, including vitamin and mineral deficiencies and loss of lean body mass, particularly muscle.

The concerns arise from new research published in Obesity Reviews. Led by Dr Marie Spreckley of the University of Cambridge, the review identified limited high-quality evidence on how nutritional advice influences calorie intake, body composition, protein consumption, and patient experiences among people using these medications.

How GLP-1 weight loss drugs work

Drugs such as semaglutide and tirzepatide, sold under brand names including Ozempic, Wegovy, and Mounjaro, work by mimicking the action of glucagon-like peptide-1 (GLP-1). This hormone is released after eating and plays a role in regulating appetite and glucose metabolism. By enhancing feelings of fullness, reducing hunger, and dampening food cravings, these medications can substantially lower energy intake.

Studies suggest that calorie intake may fall by 16–39%, helping to explain why these drugs are highly effective for people living with obesity or overweight. However, the researchers note that there has been very little detailed study of how such reductions affect overall diet quality, protein intake, or micronutrient intake, including vitamins and minerals. Existing evidence indicates that lean body mass, including muscle tissue, can account for as much as 40% of total weight lost during treatment.

Experts warn of risks without nutrition support

Dr Adrian Brown, an NIHR Advanced Fellow at UCL’s Centre of Obesity Research and the study’s corresponding author, described how these medications alter eating behaviour.

“Obesity management medications work by suppressing appetite, increasing feelings of fullness, and altering eating behaviors, which often leads people to eat significantly less. This can be highly beneficial for individuals living with obesity, as it supports substantial weight loss and improves health outcomes.

“However, without appropriate nutritional guidance and support from healthcare professionals, there is a real risk that reduced food intake could compromise dietary quality, meaning people may not get enough protein, fiber, vitamins, and minerals essential for maintaining overall health.”

Without structured support, reduced intake may unintentionally lead to inadequate consumption of nutrients needed to preserve muscle mass, bone health, immune function, and overall physical resilience.

Public guidelines versus private use

Guidance from the National Institute for Health and Care Excellence recommends semaglutide for weight management only for people who meet strict eligibility criteria, such as a body mass index of at least 35.0 kg/m² alongside obesity-related comorbidities including type 2 diabetes or cardiovascular disease. When prescribed through the NHS, the medication is intended to be delivered as part of a comprehensive programme that includes dietary changes and increased physical activity.

In reality, most people currently using GLP-1 drugs in the UK obtain them outside the NHS. An estimated 1.5 million people are now using these medications, with around 95% accessing them through private providers. In these settings, ongoing nutritional advice and follow-up support are not always consistently offered.

Rising use outpaces nutrition guidance

Dr Spreckley, who works at the Medical Research Council Epidemiology Unit at the University of Cambridge, said nutritional care has not kept pace with the rapid uptake of these therapies.

“Use of GLP-1 receptor agonist therapies has increased rapidly in a very short period of time, but the nutritional support available to people using these medications has not kept pace. Many people receive little or no structured guidance on diet quality, protein intake, or micronutrient adequacy while experiencing marked appetite suppression.

“If nutritional care is not integrated alongside treatment, there’s a risk of replacing one set of health problems with another, through preventable nutritional deficiencies and largely avoidable loss of muscle mass. This represents a missed opportunity to support long-term health alongside weight loss.”

Low intakes of essential vitamins and minerals are associated with fatigue, impaired immune function, hair loss, and increased risk of osteoporosis. Loss of lean mass, most commonly muscle, can also raise the likelihood of weakness, injuries, and falls, particularly in older adults.

Limited research leaves major questions unanswered

The review identified only 12 studies that examined diet and nutritional outcomes alongside treatment with semaglutide or tirzepatide. These studies differed widely in how dietary advice was delivered and how nutritional outcomes were measured. Many lacked standardised methods and consistent reporting, making it difficult to draw firm conclusions about best practice.

Despite the rapid expansion of GLP-1 drug use, the researchers found little robust evidence to guide clinicians on how to support people nutritionally during treatment.

Lessons from bariatric nutrition care

Given the urgent need for practical guidance, the researchers suggest that interim lessons could be drawn from nutritional care used after bariatric surgery. Procedures such as gastric banding and gastric bypass lead to similar reductions in appetite and food intake.

Dr Cara Ruggiero, a co-author from the MRC Epidemiology Unit at the University of Cambridge, said established post-surgery principles could help address current gaps.

“While GLP-1 receptor agonists are increasingly used, there remains a clear gap in structured nutritional guidance. In the interim, we can draw on well-established post-bariatric nutrition principles. Our previous work highlights the importance of prioritizing nutrient-dense foods including high-quality protein intake, ideally distributed evenly across meals, to help preserve lean mass during periods of reduced appetite and rapid weight loss.”

Equipping healthcare professionals with the nutritional knowledge to guide patients safely through this kind of rapid weight loss is the focus of professional training such as the College of Contemporary Health’s Nutrition & Weight Management Essentials, a CPD-accredited online short course.

The available evidence did not support recommending strict low-fat diets alongside GLP-1 therapies. However, some observational studies reported that people using these medications consumed relatively high amounts of total and saturated fat, suggesting a potential need for personalised guidance that aligns with national dietary recommendations.

Meal timing was rarely examined in clinical trials. Nevertheless, the researchers note that eating smaller meals more frequently may help manage side effects such as nausea and improve tolerability, particularly during the early stages of treatment.

Studying real-world experiences

The research team also emphasised the importance of incorporating the perspectives of people using GLP-1 medications into future studies. Understanding what types of information and support individuals find most helpful could improve real-world care and long-term outcomes.

To address this, the team has launched AMPLIFY – Amplifying Meaningful Perspectives and Lived experiences of Incretin therapy use From diverse communitY voices. The project aims to explore how people experience next-generation weight loss medications in everyday life.

“These medications are transforming obesity care, but we know very little about how they shape people’s daily lives, including changes in appetite, eating patterns, well-being, and quality of life,” Dr Spreckley said. “That’s what we’ll explore, working in particular with people from communities historically under-represented in obesity research, to help shape the future of obesity treatment.”

The research was funded by the National Institute for Health and Care Research, with additional support from the Medical Research Council and the NIHR UCLH Biomedical Research Centre.

CCH insights:

GLP-1 medications are licensed for the treatment of diabetes and obesity and they should be used alongside diet and lifestyle advice to improve cardiometabolic health. However, they are now commonly known as ‘weight loss drugs’, implying their primary aim is for people to lose weight. But this is kind of missing the point – the weight loss outcome is one of the mediating effects of the drugs which leads to improved health. However, if weight loss is not accompanied by a move to a healthy diet, which provides adequate levels of essential nutrients, then health outcomes will be compromised, as highlighted by this study then health outcomes will be compromised, as highlighted by this study. Closing that gap starts with clinicians themselves being confident in the fundamentals: CCH’s Nutrition & Weight Management Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) gives healthcare professionals a solid grounding in nutrition and weight management, including how to help patients meet their protein and micronutrient needs and preserve lean muscle during weight loss.

Explore Nutrition & Weight Management Essentials →

Read More

Combination of Hormone Therapy and Tirzepatide Linked to Greater Weight Loss After Menopause, Study Finds

Key Takeaways:

• Postmenopausal women using menopausal hormone therapy alongside tirzepatide lost around 35% more weight than those using tirzepatide alone in an observational study.
  
• The findings suggest a potential interaction between hormone therapy and GLP-1-based obesity medications, although causality cannot be confirmed.
  
• Researchers say the results warrant randomised clinical trials to explore mechanisms and broader cardiometabolic effects.
  
  
  

Weight management challenges after menopause

A new study led by researchers at Mayo Clinic suggests that combining menopausal hormone therapy with tirzepatide may be associated with substantially greater weight loss in postmenopausal women. The findings, published in The Lancet Obstetrics, Gynaecology, & Women’s Health, indicate that women receiving hormone therapy lost around 35% more weight while taking tirzepatide compared with those treated with tirzepatide alone.

Tirzepatide is approved by the US Food and Drug Administration for the treatment of overweight and obesity. The study’s authors say the results could expand treatment options for the many women who experience weight gain and related health risks following menopause.

Menopause is associated with accelerated age-related weight gain and a higher likelihood of developing overweight or obesity, both of which are major risk factors for cardiovascular disease, type 2 diabetes, and other long-term conditions. In addition to changes in body weight, the decline in oestrogen levels that occurs during menopause is also linked to physiological changes that may independently increase cardiovascular risk.

“This study provides important insights for developing more effective and personalized strategies for managing cardiometabolic risk in postmenopausal women,” says Regina Castaneda, MD, postdoctoral research fellow at Mayo Clinic and first author of the study.

Hormone therapy and obesity treatments

Menopausal hormone therapy is considered the most effective first-line treatment for common menopausal symptoms, such as hot flashes and night sweats, which affect up to 75% of postmenopausal women. Despite its widespread use, evidence on how hormone therapy may interact with pharmacological obesity treatments remains limited.

Previous research has suggested that postmenopausal women using hormone therapy may experience greater weight loss when treated with semaglutide, another GLP-1-based medication for obesity. However, until now, no studies had specifically examined whether hormone therapy might influence outcomes in people treated with tirzepatide.

To explore this question, Dr Castaneda and colleagues reviewed data from 120 participants with overweight or obesity who had received tirzepatide for weight management for at least 12 months. Outcomes among participants who were also using menopausal hormone therapy were compared with those of participants with similar characteristics who were not receiving hormone therapy.

Findings and limitations

According to the researchers, women using both treatments experienced markedly greater weight loss than those using tirzepatide alone.

“In this observational study, women who used menopausal hormone therapy lost about 35% more weight than women taking tirzepatide alone. Because this was not a randomized trial, we cannot say hormone therapy caused additional weight loss,” says Maria Daniela Hurtado Andrade, MD, PhD, endocrinologist at Mayo Clinic and senior author of the study.

She adds that other factors may partly explain the difference observed between the groups.

“It is possible that women using hormone therapy were already engaged in healthier behaviors, or that menopause symptom relief improved sleep and quality of life, making it easier to stay engaged with dietary and physical activity changes.”

The authors emphasise that, as an observational analysis, the study cannot establish a causal relationship between hormone therapy and enhanced weight loss. Nonetheless, they argue that the size of the observed difference is clinically meaningful.

Possible biological synergy

Dr Castaneda notes that the findings align with emerging preclinical evidence suggesting a biological interaction between oestrogen and GLP-1-based therapies.

“The magnitude of this difference warrants future studies that could help clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact. Interestingly, preclinical data suggest a potential synergy, with estrogen appearing to enhance the appetite-suppressing effects of GLP-1,” she says.

Such a mechanism could help explain why women receiving hormone therapy appeared to derive additional benefit from tirzepatide in this study.

Next steps for research

The research team plans to build on these findings through more rigorous study designs.

“Next, we plan to test these observations in a randomized clinical trial and determine if benefits extend beyond weight loss – specifically, whether hormone therapy also enhances the effects of these medications on cardiometabolic measures,” says Dr Hurtado Andrade. “If confirmed, this work could speed the development and adoption of new, evidence-based strategies to reduce this risk for millions of postmenopausal women navigating this life stage.”

The study was funded by the Mayo Clinic Center for Women’s Health Research. The full publication includes a complete list of authors, disclosures, and funding sources.

CCH insight:

This is an interesting study, but as the authors state, no conclusions can be drawn from the findings. But it does raise many questions about the possible potential synergistic effects of oestrogen and GLP-1 therapy. Establishing whether cardiometabolic benefits of GLP-1 medications are amplified, as well as weight loss, should be a priority.

Read More

More Than One in Four Adults Worldwide May Be Eligible for GLP-1 Weight-Loss Medicines, Global Analysis Suggests

Key Takeaways: 

• More than 27 percent of adults globally may be eligible for GLP-1 receptor agonists for weight management, based on pooled data from 99 countries.
  
• Eligibility is highest among women, older adults, and people living in low- and middle-income countries, raising significant questions around access and health equity.
  
• Researchers emphasise that medicines alone are not sufficient, and sustained investment in prevention and non-pharmacological obesity care remains essential.
  
  
  

A growing global obesity challenge

The worldwide prevalence of obesity has more than doubled over the past three decades, accompanied by sharp rises in weight-related conditions such as type 2 diabetes, cardiovascular disease, and several cancers. This escalating public health challenge places increasing strain on healthcare systems and national economies across the globe.

Against this backdrop, a new international study suggests that glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 medications, could play a substantial role in addressing obesity and its related complications at scale. The analysis was co-led by investigators from Mass General Brigham and aimed to estimate how many adults worldwide might benefit from these medicines.

Large-scale global data analysis

Researchers from Mass General Brigham collaborated with colleagues at Washington University School of Medicine in St. Louis and Emory University’s Rollins School of Public Health to pool household health survey data from 99 countries, collected between 2008 and 2021.

The final dataset included 810,635 adults aged 25 to 64 years, selected based on the availability of key clinical measures, including:

• Body mass index
• Blood pressure
• Diabetes biomarkers
• Diagnostic history of hypertension and diabetes
  

Eligibility for GLP-1 treatment was defined using established clinical thresholds. Adults were considered eligible if they had:

• A BMI greater than 30, or
• A BMI greater than 27 in the presence of hypertension, diabetes, or both
  
  
  

One in four adults eligible worldwide

Using these criteria, the researchers found that 27 percent of adults globally would be eligible for GLP-1 medications for weight management. Notably, around four-fifths of eligible individuals lived in low- and middle-income countries, highlighting a potential mismatch between need and access.

Eligibility varied substantially by region:

• Europe and North America showed the highest rates at 42.8 percent
• The Pacific Islands followed closely at 41.0 percent
  

Differences were also observed across demographic groups:

• Women were more likely to be eligible than men, at 28.5 percent versus lower rates among men
• Older adults showed markedly higher eligibility at 38.3 percent, compared with 17.9 percent among younger adults
  

The findings were published as a research letter in The Lancet Diabetes & Endocrinology.

Rethinking obesity through biology

Commenting on the findings, co-senior author Jennifer Manne-Goehler, MD, ScD, a physician at Brigham and Women’s Hospital and Mass General Brigham, highlighted the paradigm shift represented by GLP-1 therapies.

“There has never been such a potentially transformational and scalable tool for obesity, type 2 diabetes, and other health-related complications of obesity.”

She also reflected on the historical framing of obesity as a personal failing rather than a biologically driven disease.

“For so many decades, we told everyone the problem was you – you need to move more and eat less, then you will not struggle with this problem. GLP-1 receptor agonists have allowed us to really understand that biology is much more powerful than that, and ‘eat less, move more’ is just an oversimplified way to think about things.”

Global interest meets practical constraints

The potential of GLP-1 medicines has already been recognised by the World Health Organization, which is actively exploring ways to make these treatments more widely available as standard therapies. However, translating this promise into real-world impact depends on understanding the scale of need and addressing significant barriers to access.

Corresponding author Sang Gune K. Yoo, MD, who conducted the work while a research fellow in cardiology at Washington University School of Medicine, noted that the findings were consistent with global obesity trends.

“Given the steadily increasing prevalence of obesity, it is not surprising that our analysis found that more than one quarter of adults around the world may be eligible for this medication.”

He cautioned, however, that important questions remain unanswered.

“This medication has the potential to help many individuals, although further research is needed to better understand its long-term safety and sustainability. Access remains a major challenge as these medications are difficult to obtain in many settings. Most importantly, we must continue to invest in and develop effective non-pharmacological strategies for the prevention and treatment of obesity, an area where substantial gaps remain.”

Equity at the centre of global implementation

The study also underscores profound equity considerations. Eligibility was disproportionately high among women and people living in regions with limited healthcare resources.

Manne-Goehler highlighted the urgency of addressing these disparities.

“These socioeconomic and gender eligibility percentiles are especially staggering. As of last year, type 2 diabetes was the top cause of death for women in South Africa. There are parts of the world where women can really benefit from these medicines, and it is our job to see through their implementation.”

Co-lead author Felix Teufel, MD, from Emory University’s Rollins School of Public Health, framed access to GLP-1 therapies as a broader ethical issue.

“Global access to GLP-1s is a question of health equity. The goal is to ensure large-scale access for people who would benefit most – not just those easiest to reach.”

Beyond medicines alone

While the findings point to a potentially transformative role for GLP-1 medications in global obesity care, the authors stress that pharmacological approaches cannot replace comprehensive prevention and treatment strategies. Addressing obesity at scale will continue to require sustained investment in public health, supportive environments, and evidence-based, non-pharmacological interventions alongside new medical therapies.

CCH insight:

This study reminds us of the scale of the obesity pandemic. There are more than 1 billion people estimated to be living with obesity, according to the World Health Organisation – most of whom could in theory benefit from GLP-1 medications. The priority should be to provide access for those who are in greatest need, rather than those who can afford to pay for them. The development of oral GLP-1s is a big step, as this will increase access and bring prices down, but there is a very long way to go.

Read More

GLP-1 Weight-Loss Medications Linked to Fewer Severe Asthma Attacks in Adolescents with Excess Weight

Key Takeaways: 

• Adolescents with excess weight and asthma who were prescribed GLP-1 medications experienced around half as many asthma-related emergency room visits over one year compared with peers not taking these drugs.
  
• Use of GLP-1 therapies was also associated with reduced reliance on steroids and rescue inhalers, suggesting improved asthma control.
  
• Researchers suggest these medicines may offer a dual benefit, supporting weight management while lowering the risk of asthma exacerbations in this population.
  
  
  

Study suggests dual benefit for weight and asthma control

Severe asthma attacks among adolescents with excess weight may be significantly reduced with the use of newer weight-loss medications such as Ozempic and Zepbound, according to a new observational study.

The research found that emergency room visits for asthma were cut by more than half among teenagers who were prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. The findings were reported on 29 December in JAMA Network Open.

“Our findings suggest a potential dual benefit for this population, where a single class of medication could address both weight management and lower risk for asthma exacerbation, thereby potentially reducing the burden of two common and interconnected chronic conditions,” the researchers concluded.

The study was led by Dr Lin‑Shien Fu, chief of paediatric nephrology and immunology at Taichung Veterans General Hospital.

How the study was conducted

Researchers followed 1,070 adolescents aged 12 to 18 years who were living with excess weight and had a clinical diagnosis of asthma. Approximately half of the group had been prescribed a GLP-1 medication, while the remainder had not received a weight-loss drug.

GLP-1 receptor agonists mimic the naturally occurring GLP-1 hormone, which plays a role in regulating insulin and blood glucose levels. These medicines also reduce appetite and slow gastric emptying, contributing to weight loss.

Over a 12-month follow-up period, the researchers recorded:

• Eight asthma-related emergency department visits among adolescents taking a GLP-1 medication
  
• Nineteen asthma-related emergency visits among those not prescribed a weight-loss drug
  
  
  
  

Reduced need for asthma medications

In addition to fewer emergency visits, adolescents taking GLP-1 medications were less likely to require other treatments for asthma control.

The study found that:

• 21% of adolescents taking a GLP-1 medication required steroid treatment for asthma, compared with 31% of those not taking the drugs
  
• 32% of adolescents in the GLP-1 group needed a rescue inhaler, compared with 45% in the non-GLP-1 group
  

These differences suggest an overall reduction in asthma severity and symptom burden among those prescribed GLP-1 therapies.

Weight loss and inflammation may explain the findings

Experts not involved in the research say the observed improvements are likely linked to the degree of weight loss achieved with these newer medications.

Dr Michelle Katzow, medical director of the POWER Kids Weight Management Program and associate professor of paediatrics at Cohen Children’s Medical Center in New York City, commented on the findings in a news release.

“I think it is not surprising and not so new, except for the degree of weight loss that the drug induces is so much bigger in magnitude than we have seen before,” she said.

Dr Katzow explained that excess weight contributes to systemic inflammation, which can worsen asthma symptoms and increase the likelihood of exacerbations.

“The sort of inflammation associated with obesity predisposes somebody to having worse asthma or worse symptoms of asthma,” she said.

“If you can help people lose enough weight by whatever means, then you can improve their asthma severity.”

Implications for adolescents struggling with appetite control

Dr Katzow added that GLP-1 medications may be particularly helpful for adolescents who struggle to adopt healthy behaviours because of persistent hunger.

She noted that this is a common challenge among young people with excess weight.

“And that is true for a lot of kids,” she said. “They are just really hungry and they are thinking about food a lot. Trying to make healthier choices or eat less is really hard to do if you are hungry all the time.”

A cautious but promising signal

While the study does not establish a direct causal relationship, it adds to growing evidence that weight-loss interventions can have meaningful benefits beyond body weight alone. The findings suggest that, for some adolescents living with excess weight and asthma, GLP-1 receptor agonists may help reduce the frequency and severity of asthma exacerbations alongside supporting weight management.

Further research will be needed to confirm these findings and to better understand the long-term safety and clinical role of GLP-1 therapies in paediatric populations.

CCH insight:

The long list of benefits of GLP-1 therapy continues to grow. If obesity increases the risk of asthma, it is not surprising that GLP-1 therapy results in a reduction in hospital visits due to asthma. Further studies are needed to back up these results, and also to see if the same benefits are seen in adults, as well as adolescents.

Read More