Study Identifies Which Patients With Obesity Respond Best to GLP-1-Based Treatment
Key Takeaways:
- A Mayo Clinic study has identified a distinct biological subtype of obesity – a form of the “hungry gut” phenotype – that responds especially well to tirzepatide.
- People in this subgroup lost an average of 21.5% of their body weight after six months on tirzepatide, roughly double the 11.7% seen in other subtypes.
- The lower appetite-hormone levels traced back to reduced hormone production in the intestine rather than differences in the gut microbiome.
A step towards precision medicine for obesity
Why do some people lose a substantial amount of weight on GLP-1-based medications while others see far more modest results? A new Mayo Clinic study offers a potential answer, identifying a distinct biological subtype of obesity that responds especially well to tirzepatide – a medication that mimics two naturally occurring hormones involved in appetite and blood sugar regulation. The finding moves the field a step closer to precision medicine for obesity, where treatment is matched to an individual’s underlying biology rather than applied uniformly.
The research, published in the journal Gastroenterology, points to a future in which clinicians could predict, rather than simply hope, that a given therapy will work for a given person.
What the researchers found
The team studied 483 adults living with obesity and identified three distinct biological types of the disease. About one in four participants produced lower levels of GLP-1 and other hormones that help people feel full after eating.
This subgroup saw markedly better results on treatment. Patients in this group lost an average of 21.5% of their body weight after six months of tirzepatide, compared with 11.7% for patients in the other groups – losing nearly twice as much weight over the same period.
“Obesity is a complex disease driven by different biological mechanisms,” says senior author Andres Acosta, M.D., Ph.D., a gastroenterologist and the Delaney Family Director of the Nutrition Obesity Research Program at Mayo Clinic in Minnesota. “Our findings suggest we can begin identifying which patients are most likely to respond to specific therapies rather than treating obesity as a single disease.”
Understanding the “hungry gut” subtype
The subgroup that responded so strongly to tirzepatide shares a recognisable biological signature: people in this group produce lower levels of natural appetite-regulating hormones, experience faster stomach emptying and report greater hunger after meals.
Researchers describe this as a form of the “hungry gut” obesity phenotype, which is characterised by an abnormal duration of fullness. Rather than eating unusually large amounts at any one sitting, people with hungry-gut obesity may eat normal portion sizes but find themselves snacking more frequently, because the sense of fullness does not last as long as it should.
Because tirzepatide acts on the same appetite pathways that are underactive in this group, it appears especially well suited to addressing the biology that drives their eating patterns.
Why the underlying biology matters
The study also sheds light on why hormone levels differ in this subgroup. The researchers found that the reduced hormone levels were associated with decreased hormone production in the intestine itself, rather than with differences in the gut microbiome. That distinction offers new insight into the biology underlying this subtype and helps explain where the difference in treatment response originates.
Identifying the right therapy sooner could carry significant long-term benefits. Because obesity increases the risk of diabetes, heart disease, certain cancers and many other serious chronic conditions, matching people to the treatment most likely to help them – rather than relying on a one-size-fits-all approach – could improve long-term health outcomes.
What this means for clinical practice
The findings support growing efforts to personalise obesity treatment based on an individual’s biology. For clinicians, interpreting studies like this one increasingly depends on a firm grasp of how GLP-1-based medications act on appetite hormones and gastric emptying in the first place – the kind of grounding offered by CPD courses such as the College of Contemporary Health’s GLP-1RAs in Focus, which examines why some people respond more strongly to these treatments than others. Still, the authors are careful to note the limits of the current work. They caution that prospective studies are needed before this approach can be incorporated into routine clinical practice.
Even so, the results represent an important step towards more precise, individualised treatment for obesity – and towards a future in which people are guided to the therapy most likely to work for them from the outset.
Studies like this one land almost weekly, and making sense of them starts with understanding how GLP-1 receptor agonists actually work – from gut hormones and appetite regulation to why some people respond far more strongly than others. CCH’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work is a two-hour, CPD-accredited online course created by Prof. Mike Bewick and Nigel Hinchliffe that builds exactly this foundation, whether or not you prescribe. Explore the course and interpret the next headline with confidence.
Source: Mayo Clinic
Read More
GLP-1 Medicines for Weight Loss Reach Record Use Among US Adults
Key Takeaways:
- Eleven per cent of US adults report currently taking GLP-1 medicines for weight loss in 2026, a substantial rise from three per cent in 2024.
- Awareness of GLP-1 medicines intended for weight loss has increased to 91 per cent, while the US adult obesity rate has declined from its 2022 peak of 39.9 per cent to 36.4 per cent so far in 2026.
- Brand-name GLP-1 medicines remain the most commonly used option, but cost and insurance coverage appear to be driving some people towards compounded or custom-mixed versions.
GLP-1 use for weight loss continues to rise
The proportion of US adults who say they are currently taking GLP-1 medicines for weight loss has reached a new high in 2026, according to data from the Gallup National Health and Well-Being Index.
Eleven per cent of US adults now report current use of these medicines for weight loss purposes. This represents a significant increase from 2024, when three per cent reported current use. Lifetime use has also risen, with 15 per cent of US adults saying they have taken a GLP-1 medicine for weight loss at some point. This is an increase of nine percentage points.
The findings are based on a web survey of 5,065 US adults conducted between 28 May and 5 June 2026. The survey used the probability-based Gallup Panel, which includes respondents from all 50 US states and the District of Columbia.
How Gallup measured GLP-1 use
To assess whether people had ever used GLP-1 medicines for weight loss, Gallup asked respondents:
“Have you ever taken weight loss medications such as semaglutide (brand names Ozempic and Wegovy), liraglutide (brand name Saxenda) or tirzepatide (brand names Mounjaro and Zepbound)?”
People who answered “yes” were then asked a follow-up question to determine whether they were currently taking one of these medicines:
“Are you currently taking weight loss medications such as semaglutide (brand names Ozempic and Wegovy), liraglutide (brand name Saxenda) or tirzepatide (brand names Mounjaro and Zepbound)?”
These questions allowed Gallup to distinguish between lifetime use and current use among US adults.
FDA approvals have expanded the market
The rise in GLP-1 use follows the approval of several medicines for weight loss in the US. The Food and Drug Administration approved Novo Nordisk’s Wegovy, which contains semaglutide, for weight loss in 2021.
Since then, additional options have become available. Eli Lilly’s Zepbound, which contains tirzepatide, received FDA approval in November 2023.
As more treatment options have entered the market, public awareness has also increased. Gallup reports that 91 per cent of Americans are now aware of GLP-1 medicines intended for weight loss, up from 80 per cent in 2024.
Adult obesity has declined from its 2022 peak
Gallup’s latest findings show that the US adult obesity rate has continued to fall after reaching a record high of 39.9 per cent in 2022. So far in 2026, the adult obesity rate stands at 36.4 per cent.
Gallup describes this as a statistically meaningful decline. The trend has continued to move in the opposite direction to national GLP-1 use, which has increased over the same period.
Gallup calculates obesity using the federal standard of a body mass index of 30 or higher. BMI is calculated using respondents’ self-reported height and weight.
The organisation notes that self-reported data may produce somewhat lower estimates than studies based on randomised clinical measurements of height and weight. Gallup suggests that a “vanity effect” in how people report their own height and weight may help explain this difference. However, because Gallup has used a consistent method over time, the data still provides useful information about changes in the adult obesity rate.
Diabetes diagnoses have levelled off
While obesity levels have declined, the proportion of US adults who report having been diagnosed with diabetes has remained steady since 2023. This follows 15 years of gradual increases that occurred alongside rising obesity rates.
Gallup notes that a falling obesity rate would be expected to stabilise, but not necessarily reduce, the proportion of adults who have ever been diagnosed with diabetes. Diabetes is described in the original analysis as a lifelong disease that can be managed but not cured.
To measure diabetes prevalence, Gallup asked US adults:
“Has a doctor or nurse ever told you that you have diabetes?”
The diabetes rate includes people with Type 1 diabetes and people with Type 2 diabetes. The 2026 figures for obesity and diabetes are based on 10,091 respondents from surveys conducted from 18 February to 3 March and from 28 May to 5 June 2026.
Brand-name GLP-1 medicines remain the most common option
Among adults currently taking GLP-1 medicines for weight loss, brand-name options remain the most common.
Gallup found that 68 per cent of current use involves brand-name GLP-1 medicines such as Ozempic or Wegovy. By comparison, 19 per cent of current use involves compounded or custom-mixed versions of the medicine.
A further 12 per cent of people currently taking a GLP-1 medicine for weight loss are unsure whether they are using a brand-name medicine.
People using compounded versions report slightly higher effectiveness
Gallup also compared perceived effectiveness between people taking brand-name GLP-1 medicines and those taking compounded or custom-mixed versions.
People using compounded or custom-mixed GLP-1 medicines were slightly more likely to describe the medicine as “extremely effective”. Thirty-nine per cent of people in this group gave that response, compared with 32 per cent of people using brand-name GLP-1 medicines.
However, both groups generally regarded the medicines as effective. Seventy-seven per cent of people using compounded or custom-mixed versions said the medicine was either “effective” or “extremely effective”. Among people using brand-name GLP-1 medicines, the figure was 74 per cent.
Some people are switching from brand-name to compounded GLP-1 medicines
Although brand-name medicines continue to account for most current GLP-1 use, Gallup’s findings suggest that compounded or custom-mixed versions are gaining ground.
Among people currently using compounded or custom-mixed GLP-1 medicines, 35 per cent report having switched from a brand-name medicine. By contrast, 10 per cent of people currently using brand-name GLP-1 medicines say they switched from a compounded or custom-mixed version.
This suggests that movement towards compounded or custom-mixed GLP-1 medicines is greater than movement in the opposite direction.
Cost and insurance coverage appear to be major factors in this shift. Among people who switched from a brand-name GLP-1 medicine to a compounded version, 66 per cent cited cost or insurance coverage as their main reason for switching. Among those who switched from a compounded version to a brand-name medicine, 34 per cent cited cost or insurance coverage as the primary reason.
Wider implications for obesity and diabetes trends
The growing use of GLP-1 medicines for weight loss may point to broader health implications for adults in the US. Gallup’s analysis indicates that increased use of these medicines has coincided with a decline in the adult obesity rate and a levelling off in diabetes diagnoses after years of increases.
Previous research cited in the original analysis has shown a general alignment between GLP-1 use and declining obesity rates across age groups. One exception is adults aged 65 and older, among whom the reported effectiveness of GLP-1 medicines is lower.
Brand-name GLP-1 medicines still lead the market by a wide margin. However, the lower cost of compounded or custom-mixed versions appears to be contributing to a shift away from brand-name options for some people. This may be expanding access to GLP-1 medicines across broader sections of the population, although access remains limited.
Gallup suggests that this broader availability may be one factor helping to drive overall GLP-1 use higher in the US.
Source: Gallup
Read More
Many Who Stop GLP-1 Medications Restart Within a Year, Study Finds
Key Takeaways:
- Around 4 in 10 people with type 2 diabetes stopped their GLP-1 medication within the first year, rising to nearly 6 in 10 by the end of two years.
- Of those who stopped, more than half restarted within a year and nearly two-thirds within two years, suggesting use is often start-and-stop rather than permanent.
- Newer medications, a prescription from an endocrinologist, and fewer stomach-related side effects were all linked to a lower likelihood of stopping.
Use is more start-and-stop than assumed
People prescribed GLP-1 medications are more likely to start and stop treatment than many assume, according to a study being presented on Sunday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
“Our study asked two questions that haven’t been well answered until now: How many people with type 2 diabetes taking GLP-1 medications actually stop using them? And how many restart them?” said Sainikhil Sontha, M.S., a research associate at Boston University School of Public Health in Boston, Massachusetts.
How the study was carried out
The researchers ran a retrospective cohort study using Komodo Health US claims data covering January 2019 to June 2025. The group included adults aged 18 to 64 years with a BMI of 25 kg/m² or above and type 2 diabetes who had started liraglutide, semaglutide, or tirzepatide, and who had previously enrolled within the last year with more than six months of follow-up.
Discontinuation was defined as a gap of more than 60 days in filling a GLP-1 prescription. Obtaining a new fill after discontinuation was counted as reinitiation.
How many people stopped
“Using insurance records from more than 60,000 Americans with type 2 diabetes, we found that about 4 in 10 patients stopped their GLP-1 medication within the first year, and nearly 6 in 10 had stopped by the end of two years,” Sontha said.
But the team also found something more encouraging.
How many people restarted
“More than half of those who stopped restarted therapy within a year (41.5%), and nearly two-thirds did so within two years (58%),” Sontha said. “This suggests that for many patients, these medications aren’t being abandoned permanently; use is more start-and-stop than most people assumed.”
Who was more likely to stop
Using Cox proportional hazards models, the researchers also accounted for sociodemographic, clinical, and provider-level predictors.
Sontha and colleagues found that people on Medicaid or Medicare, people who are Black, and those experiencing nausea or other stomach-related side effects (37%) were more likely to discontinue a GLP-1 medication within a year.
What was linked to staying on treatment
People were 10% less likely to stop if their first GLP-1 medication was prescribed by an endocrinologist.
The type of medication also made a difference. People taking newer medications such as tirzepatide were 41% less likely to discontinue than those taking older drugs such as liraglutide, while people taking semaglutide were 28% less likely to discontinue anti-obesity medication use than those on older medications.
Why it matters
“This research matters because consistent use of these medications is what produces their protective effects,” Sontha said. “Stopping early may mean missed opportunities to prevent heart attacks, kidney disease progression and other complications.”
The researchers hope the findings give providers, insurers, and policymakers a clearer picture of which patients need more support to stay on GLP-1 medications.
CCH insights:
This study suggests most patients see GLP-1 medications as a temporary treatment to lose weight, rather than a long-term treatment for obesity and cardiometabolic health. It also suggests patients are not getting good advice regarding GLP-1 therapy. In the long-term, patients should be advised to reduce down to the minimum dose that enables them to maintain weight loss and also maintain gains in metabolic markers and improvements in cardiovascular risk factors, rather than stopping and restarting treatment.
Getting that judgement right – knowing when to hold a dose, when to step down rather than stop, how to keep a patient nourished when side effects bite, and how to prepare them for the long term – is exactly what our two-hour CPD course GLP-1RAs in Practice: Supporting Patients During Treatment is built around, for any clinician supporting patients across the full arc of therapy.
Source: Endocrine Society
Read More
A Simple Blood Test Could Identify the Most Effective Obesity Medication
Key Takeaways:
- A hypothesis-generating pilot study suggests that fasting blood levels of two incretin hormones – GLP-1 and GIP – may help predict how well people with severe obesity respond to semaglutide and tirzepatide.
- Low fasting GIP was linked to an optimal response to tirzepatide, while low GLP-1 combined with intermediate-to-high GIP was linked to an optimal response to semaglutide.
- The researchers stress that the findings are preliminary and should not guide prescribing until confirmed in larger, adequately powered randomised trials.
A step towards matching patients with the right medication
A straightforward fasting blood test may one day help clinicians decide which obesity medication is most likely to work for an individual patient. That is the tentative conclusion of a new hypothesis-generating pilot study published in the journal Diagnostics, which reports that fasting blood levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may help predict the therapeutic response to semaglutide and tirzepatide in people living with severe obesity.
Why obesity medications produce different responses
Obesity, characterised by excessive fat accumulation in the body, has become a global epidemic, affecting more than 650 million adults worldwide. The condition is associated with a significantly increased risk of cardiovascular disease, type 2 diabetes, certain cancers, and all-cause mortality.
Among the pharmacological options, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide, and dual GIP/GLP-1 receptor co-agonists such as tirzepatide, have shown considerable promise in addressing this challenge. One major limitation of these medicines, however, is the marked variability in response between individuals, which has prompted interest in identifying the biological mechanisms that drive this variation.
GLP-1 and GIP are the two principal incretin hormones, secreted by intestinal cells after food is eaten. GLP-1 suppresses appetite and promotes satiety through central nervous system pathways, whereas GIP regulates adipose tissue metabolism and energy expenditure. Acting synergistically, these hormones help to regulate glucose metabolism and appetite, giving them a major role in the management of obesity and type 2 diabetes.
Because the incretin system is frequently dysregulated in obesity, researchers at the University of Catania and MEDISAN, both based in Italy, designed the study to investigate whether fasting blood levels of GLP-1 and GIP could help identify people more likely to respond to semaglutide and tirzepatide.
How the pilot study was designed
The study enrolled 90 adults with a BMI greater than 40 kg/m² (class III obesity). Fasting blood samples were collected to measure each participant’s GLP-1 and GIP levels.
Each hormone was independently divided into low, intermediate, and high tertiles – a statistical division of a dataset into three equal parts – based on its distribution across the study population. Combining the GLP-1 and GIP tertiles produced nine distinct hormone profiles, each containing 10 participants. Within every profile, participants were randomly assigned to receive either semaglutide or tirzepatide, with five people allocated to each medicine per profile.
Response to treatment was assessed at six months. A reduction in body weight of less than 5% was classed as a low response, a reduction of 5–15% as an intermediate response, and a reduction of more than 15% as an optimal response.
Low incretin levels shaped treatment outcomes
The analysis showed that participants in the three profiles characterised by the low GIP tertile achieved an optimal response to tirzepatide, regardless of their GLP-1 levels. This suggests that low fasting GIP was associated with greater responsiveness to exogenous GIP receptor agonists such as tirzepatide.
For semaglutide, participants in two profiles – those characterised by a low GLP-1 tertile combined with an intermediate-to-high GIP tertile – were the only ones to achieve an optimal response. This may indicate that low endogenous GLP-1 availability leaves more GLP-1 receptors free for activation by exogenous semaglutide. The intermediate-to-high levels of endogenous GIP, meanwhile, may point to intact or compensatory incretin secretory capacity that does not interfere with the efficacy of a GLP-1 receptor agonist.
Participants in the profile characterised by high GLP-1 and high GIP tertiles achieved only a low response to both medicines. The authors suggest this may reflect a dysregulated incretin system that was not overcome by pharmacological doses within six months. They note, however, that fasting hormone measurements alone cannot distinguish between incretin secretory deficiency and receptor resistance, making this interpretation speculative.
On the clinical side, participants who achieved an optimal response to either medicine experienced significant reductions in waist circumference and improvements in insulin sensitivity. These changes paralleled the weight-loss patterns observed across the response groups, indicating clinically meaningful improvements in central adiposity and metabolic health.
How receptor occupancy may explain the findings
The observed variation in response may be explained through incretin receptor occupancy. Tirzepatide, as a dual GIP/GLP-1 receptor co-agonist, activates both receptor systems simultaneously. When GIP is present at low abundance (low fasting levels), it cannot fully occupy its receptor, potentially leaving that receptor available for exogenous tirzepatide. Once bound and activated, tirzepatide may then exert greater therapeutic effects by regulating adipose tissue metabolism, energy expenditure, and potentially central appetite regulation.
Semaglutide, which binds and activates the GLP-1 receptor exclusively, may exert its greatest effects when GLP-1 receptors are relatively unoccupied because of low levels of endogenous GLP-1. In these conditions, semaglutide may more effectively restore GLP-1 receptor signalling and deliver its anorectic, insulinotropic, and metabolic effects.
What this could mean for personalised prescribing
Taken together, the study suggests that fasting blood levels of GLP-1 and GIP were associated with the therapeutic response to semaglutide and tirzepatide in people with severe obesity, and may help identify those more likely to respond to treatment. Specifically, low GIP levels were associated with an optimal tirzepatide response, whereas low GLP-1 levels combined with intermediate-to-high GIP levels were associated with an optimal semaglutide response.
Because a single-timepoint measurement of GLP-1 and GIP cannot reveal receptor resistance, the researchers recommend treating these observations as hypothesis-generating, and highlight the need for mechanistic validation through dynamic measurements of incretin levels and receptor activity. Overall, the findings offer preliminary clinical evidence for incretin-guided, personalised pharmacotherapy that could improve treatment outcomes in obesity management.
Limitations and next steps
Several important caveats apply. This was a small, single-centre, open-label pilot study, with only five participants per treatment arm within each hormone profile. In addition, fasting hormone measurements cannot distinguish incretin secretory deficiency from receptor resistance. The authors therefore emphasise that the findings are preliminary and should not guide clinical practice until they are confirmed in larger, adequately powered randomised trials.
CCH insights:
This was a very small scale pilot study, so we can’t draw any conclusions, but it is an important step towards developing tests or measurements that can improve the personalisation of obesity care and improve the efficiency and effectiveness of obesity treatment.
Making sense of early findings like these – and understanding the incretin physiology that explains why semaglutide and tirzepatide can behave so differently from one patient to the next – is exactly what our two-hour CPD course GLP-1RAs in Focus – Why Drugs Like Ozempic Work is built for, giving any clinician the grounding to weigh new GLP-1RA evidence on its merits rather than its headlines.
Read More
Tirzepatide May Activate Calorie-Burning Brown Fat in Obesity, Trial Suggests
Key Takeaways:
- Findings from the TABFAT trial, presented at ENDO 2026, indicate that tirzepatide does more than curb appetite – it also appears to activate brown adipose tissue, a heat-producing fat that burns calories.
- Among premenopausal women with obesity, the proportion with PET/CT-detectable brown fat activity rose from 41.2% to 64.7% after 24 weeks of treatment, with no comparable change in the placebo group.
- Researchers also saw potential signs of white fat taking on more metabolically active “beige” characteristics, pointing towards future therapies that pair appetite control with increased energy expenditure.
Beyond appetite: a different question
For people taking tirzepatide, weight loss has so far been explained mainly by a reduced appetite and the smaller portions that follow. New research suggests the picture may be more complex. The medication appears to do more than dampen hunger – it also seems to switch on brown adipose tissue, a metabolically active fat that generates heat and consumes calories. The findings, described by the research team as a notable milestone in obesity research, were due to be presented on Monday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
The study set out to look past the appetite-suppressing effect that has dominated explanations of how these medications work. As lead investigator Rok Herman, M.D., of the Department of Endocrinology, Diabetes and Metabolic Diseases at University Medical Centre Ljubljana in Ljubljana, Slovenia, put it: “In the TABFAT trial, we asked a different question: beyond eating less, does tirzepatide also change how the body burns energy – specifically through brown adipose tissue, a metabolically active type of fat that produces heat and consumes calories?”
What is brown adipose tissue?
Brown adipose tissue, often referred to as brown fat, was for many years thought to disappear after infancy. Its presence in adults was only confirmed through imaging studies in the late 2000s. Unlike ordinary white fat, which mainly stores energy, brown fat burns it to produce heat. In people living with obesity this tissue is markedly suppressed, and until now moderate cold exposure has been its strongest recognised activator.
How the TABFAT trial was designed
The team led by Herman ran a randomised, placebo-controlled clinical trial in premenopausal women with obesity. To assess what was happening within the tissue itself, the researchers used cold-stimulated PET/CT imaging alongside MRI scans, measuring brown adipose tissue activity both before treatment and after 24 weeks. Using more than one imaging method allowed the team to capture different aspects of brown fat biology rather than relying on a single measure.
What the scans revealed
The results pointed to a measurable change in how the body handled energy, not simply how much participants ate. “We found that tirzepatide significantly increased brown adipose tissue activity and volume, and it also showed potential signs of converting white subcutaneous fat into more metabolically active ‘beige’ fat,” Herman said.
The shift was clear in the imaging data. Tirzepatide increased PET/CT-detectable brown adipose tissue activity from 41.2% to 64.7% of participants, while no comparable change was seen in the placebo group. The researchers were reassured that the effect showed up across the different scanning techniques used. “We were also encouraged by the consistency of the signal across other imaging modalities employed in the study that may capture different component of brown fat biology,” Herman added.
Why this matters for obesity care
The findings suggest a fuller account of how the latest anti-obesity medications work. Rather than acting on appetite alone, tirzepatide also appears to influence how much energy the body burns at the level of the tissue. “This adds a new layer to how we understand the new generation of anti-obesity medications,” Herman said. “They are not only appetite suppressants – tirzepatide also appears to modulate energy expenditure at the tissue level, opening a plausible path toward future therapies that combine appetite regulation with thermogenic activation.”
Looking ahead
Herman suggests that future research should measure, study and potentially enhance brown and beige fat activity, treating it as a specific target within a more tailored approach to obesity care. If brown fat activation can be reliably encouraged and built upon, it may complement the appetite-related effects already well documented, broadening the options available to people living with obesity.
CCH insights:
This is a fascinating study. For many years researchers have been looking at ways to stimulate brown adipose tissue (BAT) activity, or enhance beige adipose tissue production, without much success, except for asking people to spend hours in the cold every day. Now it seems we may have stumbled across an answer by accident. The question now is, how does tirzepatide have this effect, and could we develop other agents which act in a similar way to activate BAT and beige adipose tissue without affecting gastro-intestinal function and/or appetite? This would enable us to widen the range of tools for obesity care.
Following where questions like this lead – how a dual GIP/GLP-1 agent acts on energy expenditure and not just appetite – starts with a solid grounding in the underlying physiology, which is exactly what our two-hour CPD course GLP-1RAs in Focus – Why Drugs Like Ozempic Work is built to give any clinician wanting to understand these medications at the mechanistic level.
This article summarises findings presented at ENDO 2026, the Endocrine Society’s annual meeting. Research presented at conferences may not yet have completed full peer review.
Source: Endocrine Society
Read More
People with Obesity Tend to Move Less After Starting GLP-1 Medications, Study Finds
Key Takeaways:
- Daily step counts and moderate-to-vigorous activity both dropped after adults with obesity started a GLP-1 receptor agonist, with no sign that weight loss prompted people to move more.
- Because these medications strip away lean muscle as well as fat, staying active matters for protecting strength and long-term health rather than being an optional extra.
- This is the first large study to draw on data from wearable fitness trackers in adults taking GLP-1 medications, and its authors argue for targeted support that builds activity in alongside treatment.
A counterintuitive picture of how people move
It is tempting to assume that as the weight comes off, people naturally become more active. New findings suggest the opposite may be closer to the truth. Adults with obesity who were losing weight on glucagon-like peptide-1 (GLP-1) receptor agonist medications significantly reduced their physical activity, according to a study being presented on Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
That matters because activity is one of the main safeguards against an unwanted side effect of these treatments. GLP-1 receptor agonists such as semaglutide, liraglutide, dulaglutide and tirzepatide reduce not only fat but also lean muscle mass. This makes physical activity essential for preserving strength and long-term health, according to study lead Sajana Maharjan, M.D., of HSHS St. John’s Hospital in Springfield, Illinois.
How the study was carried out
The work was a retrospective pre–post cohort study, meaning researchers compared the same individuals before and after they started treatment. It drew on data from the National Institutes of Health’s All of Us Research Program, which links participants’ electronic health records with their Fitbit activity data, allowing the team to track real-world movement rather than relying on self-reported habits.
Among the 1,950 adults with obesity who started a GLP-1 medication, researchers studied 753 people who had enough wearable-device data for analysis. The cohort was predominantly female, at 78.6 per cent, with a mean age of 52.7 years.
For each person, the researchers compared physical activity before and after treatment began, focusing on two measures: daily step counts and minutes of moderate-to-vigorous physical activity (MVPA).
Steps and active minutes both fell
The direction of travel was clear. On average, daily steps decreased from 5,047 to 4,487 per day, while MVPA minutes fell from 28 to 22 per day after people began a GLP-1 receptor agonist medication.
Crucially, the study found no evidence that weight loss from these medications led to increased physical activity. The expected rebound in movement simply did not appear in the data.
Who saw the biggest changes
The decline was not evenly spread. The largest drops were seen in men and in people living with joint or muscle pain. By contrast, factors such as age, heart failure or a prior stroke did not change the results, suggesting the pattern held across a fairly broad range of circumstances.
Why activity cannot be an afterthought
For Dr Maharjan, the practical message is that exercise needs to be designed into treatment rather than left to chance:
“While many assume that weight loss leads naturally to increased physical activity, our study suggests otherwise. The findings in our study reinforce that exercise cannot be optional for people taking these medications. People need targeted interventions that encourage physical activity alongside medication for obesity.”
Given that GLP-1 receptor agonists reduce lean muscle alongside fat, a fall in activity could compound the loss of strength, making structured support for movement an important part of care rather than a nice-to-have.
A first for wearable-data research
The study stands out for its method as much as its findings. It is the first large study analysing data from wearable fitness trackers among adults taking GLP-1 receptor agonists, offering a more objective window into everyday behaviour than questionnaires alone can provide. As these medications become more widely used, that kind of real-world evidence is likely to shape how clinicians and patients approach physical activity during treatment.
CCH insights:
This is a very interesting study, but it throws up more questions than answers. Firstly, were any of the participants receiving diet and lifestyle advice as they are supposed to? GLP-1 medications are designed as an adjunct to such advice, but these results suggest it was probably lacking from these patients’ treatment. Another question, of course, is why did physical activity drop? Further research is needed to understand what is the underlying reason for these results. But most importantly, this study is a reminder that GLP-1 therapy is not just about taking the medication, it requires diet and lifestyle advice and ongoing support and monitoring.
Source: Endocrine Society
Read More
Semaglutide Shows Benefit in Severe, Long-Standing Treatment-Resistant Obesity, Trial Finds
Key Takeaways:
- Weekly semaglutide (2.4 mg) cut BMI by an average of 19 per cent – around 22.3 kg – over 68 weeks in young adults with treatment-resistant severe obesity.
- Benefits went beyond weight, with large falls in total, abdominal and liver fat and in metabolic syndrome severity, lowering cardiovascular and type 2 diabetes risk.
- The drug was safe and well tolerated, with only mild, short-lived side effects and no related dropouts.
A promising option for hard-to-treat obesity
A weekly dose of semaglutide (2.4 mg) leads to a clinically significant reduction in body mass index (BMI) and related health outcomes in young adults living with severe obesity who are resistant to treatment following hospital-based, non-pharmacological obesity care during childhood. That is the finding of a randomised controlled trial being presented at this year’s European Congress on Obesity (ECO).
The study, led by researchers from the University of Copenhagen and Holbæk Hospital in Denmark, highlights the importance of identifying as early as possible the children who are resistant to hospital-based obesity care and who may benefit from the timely addition of semaglutide or other glucagon-like peptide-1 receptor agonists (GLP-1 RAs).
Semaglutide and other GLP-1 RAs work by mimicking naturally produced incretin hormones. These hormones help to lower blood sugar levels after a meal and reduce appetite, prompting people to eat less.
Why new strategies are urgently needed
Children living with obesity are five times as likely to be living with obesity in adulthood as their healthy-weight counterparts [1]. Obesity that begins in early childhood carries significant health risks in early adulthood, including early-onset type 2 diabetes, cancer, cardiovascular disease and a reduced quality of life.
Hospital-based, non-pharmacological obesity care – which involves supporting children living with obesity and their families to improve health and thriving during growth and development – has been shown to reduce childhood obesity. However, around one in four children are more difficult to treat, and any reduction in the degree of obesity is hard to maintain. New, effective and safe treatment strategies are therefore urgently needed.
Inside the RESETTLE trial
In the new RESETTLE trial – a randomised, placebo-controlled, double-blind study – the researchers investigated the effect of semaglutide treatment in young adults (aged 18 to 28 years) who were still living with severe obesity despite at least one year of treatment at the Children’s Obesity Clinic, European Centre for Obesity Management, at Holbæk Hospital in Denmark.
The study involved 246 young adults (average age 23 years, 59 per cent female) who had been included in the HOLBAEK Study [2]. Participants were randomised into four different groups, based on how they had previously responded to the paediatric hospital-based treatment programme and on their current BMI:
- 82 participants with a low response to childhood obesity care (a change in BMI that was not enough to improve their health) and who were currently living with obesity as young adults (BMI of 30 kg/m² or above).
- 80 participants with a medium response to childhood obesity care and living with obesity as young adults (BMI of 30 kg/m² or above).
- 34 participants with a high response to childhood obesity care who were not living with obesity as young adults (BMI below 30 kg/m²).
- 50 participants from a population-based reference group who had a normal weight development in childhood.
What the assessments measured
All participants, regardless of their response group, underwent examinations of cardiometabolic biomarkers (waist circumference; lipids in the blood, including cholesterol; blood glucose; and blood pressure), full-body dual-energy x-ray absorptiometry (DXA) imaging of body composition, and magnetic resonance imaging (MRI) of liver and visceral (abdominal) fat.
The 162 participants in the low- and medium-response groups – who had poorer health outcomes than the high-response and normal-BMI-development groups – were randomly assigned to either weekly injections of semaglutide (2.4 mg; 54 in the low-response group and 55 in the medium-response group) or placebo (28 and 25 respectively) over 68 weeks. In total, 152 participants (94 per cent) attended the final visit.
Results: large reductions in BMI and weight
After 68 weeks, semaglutide led to an average decrease in BMI of 19 per cent (average weight loss of 22.3 kg) in both the low- and medium-response groups, compared with placebo.
In the low-response group, average BMI among those taking semaglutide fell by 7.3 kg/m² (from 40.5 kg/m²), compared with a minor increase of 0.5 kg/m² in the placebo group. Similarly, in the medium-response group, average BMI decreased by 6.7 kg/m² (from 38.0 kg/m²) among those taking semaglutide, but rose by 0.6 kg/m² among those given placebo (see figure 1 in the full abstract).
Beyond weight: fat and metabolic health
Participants in the low- and medium-response groups who received semaglutide also saw substantial improvements in total fat mass (-17 kg and -15 kg respectively), abdominal fat (-48 per cent and -41 per cent) and liver fat (-39 per cent and -34 per cent) compared with placebo – all key factors in reducing obesity-related health risks.
In addition, these participants experienced substantial improvements in their metabolic syndrome severity score (-0.80 and -0.58), a measure that integrates lipids, blood pressure, fasting glucose and waist circumference into a single value. This reflects a substantial reduction in the risk of developing cardiovascular disease and type 2 diabetes.
Safety and tolerability
Semaglutide was safe and generally well tolerated. Gastrointestinal side effects, such as nausea and abdominal pain, were the most common. However, most side effects were manageable, resolved over time, and did not lead to participants dropping out of the trial.
What the researchers say
“By reducing the degree of obesity and improving cardiometabolic health irrespective of prior response to childhood obesity care, GLP-1 based treatment could help more young people with severe obesity to reduce their burden of obesity-related complications in early adulthood,” said author Joachim Holt from the University of Copenhagen.
According to study lead Professor Signe Sørensen Torekov at the University of Copenhagen, “Severe obesity in young people is a complex, chronic disease with serious health consequences. GLP-1 based treatment offers a promising option for managing severe obesity in young people who are resistant to prior hospital-based non-pharmacological care. Importantly, supporting families to implement increased physical activity and health behaviours should remain the foundation of all treatments for childhood obesity and prevention of obesity across generations.”
Head consultant Jens-Christian Holm, of the Children’s Obesity Clinic, European Centre for Obesity Management, Holbæk University Hospital, adds that, “Childhood obesity is a chronic disease resulting in numerous complications reducing physical, mental and social thriving during growth and development. Being able to optimise obesity treatment with the addition of drugs in selected patients to improve health is a worldwide imperative.”
CCH insights:
Once again, GLP-1 therapy delivers excellent results, providing the necessary change in appetite that allowed these young people to make the behavioural changes needed to lose weight and improve health, when previously they had been unable to do so. And it is not just about losing weight, with significant improvements in metabolic and cardiovascular disease risk factors.
References:
[1] Predicting adult obesity from childhood obesity: a systematic review and meta‐analysis – Simmonds – 2016 – Obesity Reviews – Wiley Online Library
[2] The HOLBAEK Study includes more than 4,000 Danish children and adolescents with and without obesity (Study Details | NCT02852694 | Reduce Risk for Crohn’s Disease Patients | ClinicalTrials.gov).
Bariatric Surgery Delivers Greater Weight Loss and Disease Remission Than GLP-1 Drugs, Large Analysis Finds
Key Takeaways:
- A large real-world analysis involving more than 430,000 patients found that metabolic and bariatric surgery produced substantially greater weight loss than GLP-1 medications after 12 months.
- Surgery was associated with higher remission rates for obesity-related conditions including type 2 diabetes, hypertension and high cholesterol.
- Researchers and clinicians said GLP-1 medications represent an important advance in obesity care, but cautioned that they should not be viewed as a replacement for metabolic and bariatric surgery in people requiring more substantial and durable outcomes.
Surgery outperformed GLP-1 drugs across key outcomes
Metabolic and bariatric surgery may provide significantly greater weight loss and higher rates of obesity-related disease remission than glucagon-like peptide-1 receptor agonist medications, according to a major new real-world comparison presented at the American Society for Metabolic and Bariatric Surgery (ASMBS) Annual Meeting 2026.
The systematic review and analysis, described as one of the largest and most comprehensive comparisons of the two treatment approaches to date, evaluated data from 30 clinical studies involving more than 430,000 patients. Researchers found that although both treatments produced meaningful clinical benefits for people living with obesity, metabolic and bariatric surgery consistently outperformed GLP-1 therapies across all major outcomes assessed.
The research was conducted by investigators from Yale School of Medicine, Coreva-Scientific, Vanderbilt University and UT Health San Antonio.
Greater weight loss after surgery
According to the findings, people who underwent metabolic and bariatric surgery experienced more than 20% greater weight loss at 12 months compared with those treated with GLP-1 receptor agonist medications.
Researchers also reported that surgery was linked to substantially higher remission rates for several obesity-related health conditions. Compared with GLP-1 therapy, metabolic and bariatric surgery was associated with:
- 42% higher remission rates for type 2 diabetes
- 12.8% higher remission rates for hypertension
- 20.8% higher remission rates for high cholesterol
The analysis focused specifically on studies that directly compared bariatric surgery with GLP-1 receptor agonists. Studies that combined surgery and medication therapies were excluded from the review.
The primary endpoint examined was weight loss at 12 months. Secondary endpoints included remission of obesity-related conditions such as type 2 diabetes, hypertension and hyperlipidaemia.
Researchers highlight durability of surgical outcomes
The study authors noted that although GLP-1 medications have transformed obesity treatment and expanded evidence-based care options, metabolic and bariatric surgery continues to deliver greater and more durable results for many patients.
“While GLP-1 medications are an important advance, they do not match the magnitude or durability of outcomes achieved with metabolic and bariatric surgery, which remains one of the most underutilized treatments in medicine. Once the medications are discontinued, whether due to side effects, cost or other factors, their benefits often diminish or disappear, whereas the benefits of surgery endure.” – John M. Morton, MD, MPH, FASMBS, Study Co-Author, Professor of Surgery and Vice-Chair, Quality, Surgery at Yale School of Medicine
The findings add to ongoing discussions within obesity care about how best to position GLP-1 therapies and surgical interventions within long-term treatment pathways.
Evidence gap in direct comparisons
Despite the rapid growth in the use of GLP-1 medications such as semaglutide and tirzepatide, researchers noted that direct comparisons between these drugs and bariatric surgery remain limited.
The review involved a comprehensive search of PubMed and EMBASE databases to identify relevant studies comparing the two treatment approaches.
Commenting on the findings, an independent obesity surgery expert said the analysis helps address a major evidence gap in the field.
“Despite the explosive growth of GLP-1 drugs, no randomized controlled trials have directly compared them to bariatric surgery. This analysis helps fill that evidence gap,” said John Scott, MD, FACS, FASMBS, clinical professor of surgery at the University of South Carolina School of Medicine Greenville and metabolic and bariatric surgery director for Prisma Health, who was not involved in the study.
“GLP-1s have expanded evidence-based treatment options, but they should not be seen as a replacement for surgery – especially for patients who require the level of outcomes that only metabolic and bariatric surgery can provide.”
Expanding treatment options in obesity care
The findings come amid growing global interest in obesity treatment strategies as the use of GLP-1 receptor agonists continues to rise rapidly. Medications in this class have demonstrated significant effectiveness for weight reduction and metabolic health improvement, but concerns remain regarding long-term adherence, cost, side effects and weight regain after discontinuation.
Metabolic and bariatric surgery, meanwhile, has long been associated with substantial and sustained weight loss as well as improvements in obesity-related conditions such as type 2 diabetes and cardiovascular risk factors. However, experts have repeatedly argued that surgery remains significantly underutilised despite its established effectiveness.
The researchers concluded that while both treatment approaches play an important role in obesity management, metabolic and bariatric surgery continues to provide the most substantial improvements in weight loss and disease remission outcomes based on current comparative evidence.
Source: American Society for Metabolic and Bariatric Surgery
Read More
Can Less Be More? Reduced GLP-1 Dosing May Sustain – and Even Enhance – Weight Loss
Key Takeaways:
- Structured reduction in GLP-1 receptor agonist dosing frequency may allow continued weight loss while lowering treatment burden
- Cardiometabolic improvements achieved during weekly dosing appear to be maintained with less frequent dosing
- Early evidence suggests some individuals may not require high or frequent dosing to sustain weight loss, although larger trials are needed
A new approach to GLP-1 treatment
Emerging evidence suggests that reducing the frequency of glucagon-like peptide-1 receptor agonist (GLP-1 RA) dosing may still deliver sustained benefits for people living with obesity. Data presented at the Obesity Medicine Association’s annual conference indicate that a structured, gradual de-escalation strategy could maintain, and in some cases enhance, weight loss outcomes while reducing the burden of ongoing treatment.
This finding challenges the prevailing assumption that continuous, high-frequency dosing is required to preserve the benefits of these therapies.
Continued weight loss despite reduced dosing
The research, led by Mitch Biermann, MD, PhD, examined outcomes in individuals who transitioned from weekly GLP-1 RA dosing to less frequent schedules. Reflecting on the results, Biermann noted:
“What I found was actually surprising, where in addition to losing weight initially on the weekly regimen, people actually lost further weight on the every-other-week regimen,” Mitch Biermann, MD, PhD, an obesity medicine physician and scientist at Scripps Health, told Healio. “I was just hoping people would break even, not get an additional 2% weight loss.”
This observation suggests that, for some individuals, reduced dosing frequency does not simply preserve prior weight loss but may contribute to further reductions.
Addressing a common patient concern
The study was partly motivated by a frequent question from patients considering GLP-1 therapy. As Biermann explained:
“The No. 1 question patients have when they’re deciding to start one of these medicines is, ‘Do I have to be on this every week for the rest of my life? Do I have to take this forever?’” he said. “Patients ask that about certain medicines and not others. It usually correlates with the stigma around the disease. They always ask about it for weight loss medicine.”
This highlights an important dimension of obesity care – long-term treatment expectations and the role of stigma in shaping patient concerns.
Study design and patient cohort
The analysis was based on a retrospective case series involving 30 adults who had been prescribed either semaglutide (Wegovy or Ozempic) or tirzepatide (Mounjaro). All participants had experienced a plateau in weight loss during standard weekly treatment.
Participants agreed to reduce their dosing frequency while maintaining their effective dose. The adjusted schedules included:
- Every 10 to 14 days (n = 6)
- Every two weeks (n = 17)
- Longer than every two weeks (n = 7)
The mean follow-up period was 36 weeks.
Body composition and weight outcomes
Following the transition to reduced dosing, participants continued to lose weight, with reported reductions of 72.4 ± 2.2 kg (P < .01). In addition to overall weight loss, improvements were observed in body composition:
- Reductions in body fat mass
- Decreases in average percentage body fat
- Lower truncal fat mass
At the same time, skeletal muscle mass increased slightly from 30.33 ± 1.27 to 30.63 ± 1.25, suggesting that weight loss was not associated with disproportionate muscle loss.
Sustained cardiometabolic benefits
Importantly, key metabolic improvements achieved during weekly dosing were maintained after reducing treatment frequency:
- Glycaemic control: HbA1c improved from 5.6% ± 0.13% before treatment to 5.1% ± 0.1% during weekly dosing (P < .001), with no change during reduced dosing
- Triglycerides: Levels decreased from 121 ± 11.3 mg/dL to 84.3 ± 9.6 mg/dL during weekly dosing (P < .001) and remained stable at 74.8 ± 4.1 mg/dL
- Mean arterial pressure: Reduced from 90.5 ± 2 mm Hg to 84.8 ± 2.1 mm Hg (P < .05), remaining stable at 85.1 ± 1.5 mm Hg during maintenance
The proportion of participants meeting criteria for metabolic syndrome also declined, from nearly 83% before treatment to 68% during weekly dosing and 58.6% following dose reduction.
Interpreting the findings
The study authors suggest that lower levels of GLP-1 receptor stimulation may be sufficient to maintain weight loss once it has been achieved. Biermann offered the following interpretation:
“that you don’t need much of these hormones to maintain weight loss, even though you need a lot of them to reduce weight.”
He also drew a parallel with physical activity:
“Exercise doesn’t cause people to lose a ton of weight. It causes people to maintain their weight if they lose it by another method for the most part,” he said. “And that matches this hormone data, because that 30% increase [in hormone levels] you get on GLP-1s from exercise is probably enough to maintain your weight loss.”
Limitations and considerations
The findings should be interpreted cautiously. The study was small, non-randomised, and based on a retrospective case series. In addition, the cohort lacked diversity, with only four participants not identified as white and just two individuals living with class II or III obesity.
These limitations mean that the results may not be generalisable to broader populations.
Implications for clinical practice
Despite its limitations, the study offers a potentially important insight into long-term obesity management. Gradual dose reduction may represent a viable strategy for some individuals seeking to balance efficacy with treatment burden.
As Biermann concluded:
“I think it’s an option that works for many people, [particularly] when we don’t study how to stop medicine in general,” Biermann told Healio.
“I think it’s nice to have some published data on the average effectiveness of this strategy, even though it’s not a randomized controlled trial,” he said.
Looking ahead
Further research, particularly large-scale randomised controlled trials, will be essential to determine whether reduced dosing strategies can be safely and effectively implemented in routine care. For now, these findings provide an early signal that long-term GLP-1 therapy may not need to follow a one-size-fits-all model.
Source: Healio
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