Major Weight Loss Alters Brain Structure in People With Obesity, One-Year Study Finds
Key Takeaways:
- Adults with obesity who lost at least 40% of their excess weight over one year showed greater increases in subcortical grey matter volume than those who lost less, alongside significant improvements in blood sugar control, cholesterol, liver enzymes and inflammation.
- Greater excess weight loss was associated with reductions in cortical and subcortical T1 relaxation times, a possible marker of improved grey matter tissue health, although the between-group difference in subcortical volume did not survive correction for multiple comparisons.
- Cognitive performance did not differ significantly between groups after one year, and the researchers say longer, larger studies are needed to establish whether early structural brain changes lead to measurable cognitive benefits.
Weight loss and the brain: a growing question
People with obesity who lost at least 40% of their excess weight over one year showed measurable gains in brain structure, particularly in subcortical grey matter volume, according to a prospective cohort study conducted at New York University Grossman School of Medicine’s Brain, Obesity & Diabetes Laboratory. These changes were accompanied by substantial improvements in blood sugar control, cholesterol and inflammation.
The findings, published in Obesity Science & Practice, arrive at a time when the use of weight-loss medications in the United States doubled from 0.76 million to 1.51 million users between 2017 and 2024. As more people undergo major weight loss, understanding how it affects the brain has become an increasingly urgent question.
How the study was designed
The study enrolled 84 adults with obesity from weight-loss programmes at NYU Langone Medical Center and NYU Langone Brooklyn between 2018 and 2023. Each participant was followed for approximately one year, with identical evaluations carried out at baseline and at follow-up.
Participants were aged between 33 and 59 and had body mass index (BMI) values between 30 and 50 kg/m², with diagnoses of type 2 diabetes, prediabetes or insulin resistance. Rather than randomising participants to a specific treatment, the researchers categorised them after the fact according to how much weight they lost. In total, 54 people who achieved 40% or greater excess weight loss formed the weight-loss group, while 30 people who lost less than this threshold formed the non-weight-loss group.
Excess weight was calculated as the difference between each participant’s actual weight and the weight corresponding to a BMI of 25 kg/m². On average, the weight-loss group lost 64.39% of their excess weight and 23.62% of their total body weight, falling from a mean of 245.42 pounds at baseline to 186.51 pounds at follow-up. By comparison, the non-weight-loss group lost an average of 9.71% of excess weight and 3.38% of total body weight.
Treatment approaches varied considerably. Across the overall cohort, 57 participants underwent bariatric surgery, mostly sleeve gastrectomy, while 27 received behavioural or medical interventions. A total of 25 participants used GLP-1 receptor agonists as adjunctive therapy across both approaches.
Comparing the two groups at baseline
At the start of the study, the two groups were closely matched. They did not differ significantly in age, education, socioeconomic status, weight, waist circumference or the prevalence of metabolic syndrome, which affected 83.3% of the non-weight-loss group and 68.5% of the weight-loss group. Around three-quarters of the cohort were female, reflecting the clinical population seeking obesity treatment.
A small number of baseline differences emerged, with the weight-loss group showing higher BMI, LDL cholesterol, cholesterol ratio and alanine aminotransferase (ALT). However, most of these differences disappeared after adjustment for multiple comparisons, leaving only LDL cholesterol and ALT statistically distinct between the groups.
Assessments and brain imaging
Each participant underwent a physical examination, fasting blood tests, a five-sample oral glucose tolerance test, cognitive testing and a standardised 3T MRI session that included a structural MP2RAGE scan.
The researchers processed the images using FreeSurfer software, measuring regional brain volumes and generating quantitative T1 maps, a technique sensitive to changes in tissue. They paid particular attention to regions vulnerable to Alzheimer’s disease, including the inferior parietal and inferior temporal cortices, the posterior cingulate cortex and the hippocampus. These areas were selected because they are sensitive to the metabolic, vascular and inflammatory insults that are also common in obesity.
Marked improvements in metabolic health
The metabolic results were striking. Compared with the non-weight-loss group, participants who lost the most weight showed significantly greater reductions in BMI, waist circumference, HbA1c, fasting glucose, fasting insulin, HOMA-IR and C-reactive protein. They also showed improved insulin sensitivity, measured by QUICKI and ISI, a healthier lipid profile with higher HDL and lower LDL cholesterol, and improved liver enzymes. Most of these effects remained significant after correction for multiple comparisons.
At follow-up, the prevalence of metabolic syndrome was significantly lower in the weight-loss group than in the non-weight-loss group. Blood pressure, however, did not change significantly between groups, probably because many participants were already taking antihypertensive medications at baseline.
For healthcare professionals supporting people living with obesity and related metabolic conditions such as type 2 diabetes and insulin resistance, findings like these highlight the wide-ranging benefits of effective weight management. CCH’s Obesity Essentials course offers a grounding in supporting people living with obesity, helping clinicians place evidence like this in the context of everyday practice.
Changes in brain structure
The brain findings were more nuanced. The clearest signal appeared in subcortical grey matter volume. After adjusting for age and the interval between scans, the weight-loss group showed significantly greater increases in subcortical grey matter than the non-weight-loss group, and this effect persisted when T1 relaxation time was added as a covariate.
Within the weight-loss group, subcortical grey matter increased significantly over the year, while the non-weight-loss group showed a significant decline in the composite volume of Alzheimer’s-vulnerable regions. However, the between-group difference in subcortical volume did not survive correction for multiple comparisons, and the researchers stress that the within-group changes in Alzheimer’s-vulnerable regions should be regarded as preliminary.
T1 relaxometry offers further evidence
T1 relaxometry provided a second line of evidence. Longer T1 relaxation times are generally interpreted as a marker of tissue damage. In this study, higher percentage excess weight loss was associated with greater reductions, indicating improvements, in both cortical and subcortical T1 relaxation values. This aligns with earlier findings in adolescents with obesity.
Taken together, the authors write, the results suggest that weight loss is associated with improvements in the volume and possibly the health of grey matter, particularly in subcortical regions. This is consistent with existing literature showing that higher BMI is linked to grey matter atrophy.
No clear effect on cognition yet
Cognition told a different story. Cognitive performance did not differ between the groups at baseline or at follow-up. Although the weight-loss group showed numerically greater improvements in memory composite scores, these did not reach statistical significance and were highly variable.
The authors suggest that a one-year follow-up may be too short for subtle structural changes to translate into measurable cognitive benefits, and that detecting such effects is likely to require larger, adequately powered cohorts with longer follow-up periods.
Limitations and next steps
The study has several important limitations. It was non-randomised, and group assignment was determined post hoc based on weight loss, meaning unmeasured confounding cannot be fully ruled out. The modest sample size prevented subgroup analyses, including any examination of sex-dependent effects, and the one-year follow-up was designed to capture short-term changes rather than long-term trajectories.
The researchers note that longer studies will be needed to determine whether weight loss alters the course of cognitive decline and neurodegenerative risk, and whether the structural brain changes observed precede measurable cognitive benefits.
Even so, the parallel improvements in peripheral metabolic markers and central neuroimaging measures raise the possibility that weight loss may influence neurobiological pathways relevant to neurodegenerative risk before cognitive changes emerge. According to the authors, this provides a rationale for extended follow-up to test the durability and functional significance of these early structural signals.
CCH insight
Weight loss in this study was achieved through a range of approaches, from bariatric surgery to behavioural and medical interventions, and the benefits extended well beyond the scales. Obesity Essentials from The College of Contemporary Health helps healthcare professionals build the knowledge and confidence to support people living with obesity across these different pathways.
Explore Obesity Essentials and enrol today →
Source: Obesity Science & Practice
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Study Finds Higher Rates of Nail Detachment Among People Taking GLP-1 Medications
Key Takeaways:
- In a study of 1,904 people across four countries, nail detachment was reported by 39 per cent of people taking GLP-1 medications, compared with 9 per cent of people with type 2 diabetes or obesity who had never taken them, although around half of those taking the drugs reported nail problems before treatment began.
- The study was cross-sectional and based on self-reported symptoms, so it shows an association rather than proving that GLP-1 medications cause nail changes.
- Dermatologists describe the changes as frequent and usually benign, and advise people who notice nail, hair or scalp changes to speak with their doctor rather than stop treatment on their own.
A new question for people starting GLP-1 treatment
When a person begins a new medication and notices a change in their body, a natural question often follows: is the drug responsible? Changes to the nails can prompt exactly that question.
In a new study, researchers set out to investigate whether nail problems are more common among people taking GLP-1 medications, which are used to treat obesity and type 2 diabetes. Their analysis of 1,904 people across four countries found a notable difference.
Nail detachment was reported by 39 per cent of people taking GLP-1 medications, compared with 9 per cent of people with type 2 diabetes or obesity who had never taken the drugs. However, around half of the people taking the medications reported having nail problems before their treatment began.
The findings were presented at the European Academy of Dermatology and Venereology (EADV) Congress 2026 in Vienna.
How the study was designed
The researchers compared 575 people taking GLP-1 medications with 1,329 people with type 2 diabetes or obesity who had never used them. Participants were recruited across France, the United States, Brazil and Mexico.
According to an EADV press release, 66 per cent of people taking GLP-1 medications reported at least one nail disorder, compared with 53 per cent of the control group. Nail discolouration was reported by 46 per cent of people taking the medications, compared with 17 per cent of controls.
“Our findings show a clear association, but they also underline an important point,” says study author Charles Taïeb, the managing director of the European Market Maintenance Assessment.
“Not everything that happens during GLP-1 treatment is necessarily caused by the treatment itself.”
Why the findings cannot prove cause and effect
The study relied on participants describing their own symptoms. It was cross-sectional, meaning it captured participants’ experiences at a single point in time rather than following them through treatment with standardised dermatological examinations. As a result, it cannot establish that the medications caused the changes reported.
The extent of the nail detachment described in the study is also unclear. The researchers have not specified whether the term covers partial separation from the nail bed, complete nail loss, or both. The information currently available also does not distinguish between fingernails and toenails.
Understanding nail detachment
In general, separation of the nail plate from its bed is known as onycholysis. DermNet explains that it can affect the fingers or toes and has several possible causes, including injury, skin disease and infection. However, this general background does not establish which conditions participants in this particular study experienced.
The 39 per cent figure should therefore not be interpreted as evidence that nearly four in ten people taking GLP-1 medications lost their nails completely. Nor does it estimate the likelihood that a person newly starting the medication will develop the problem.
Accounting for other factors
When analysing the results, the researchers accounted for dermatological conditions and nutritional deficiencies. Some of the associations weakened as a result, but nail detachment and discolouration remained around two to three times more frequent among people taking GLP-1 medications, according to the press release.
The exact adjusted estimates and confidence intervals have not been provided. Without them, the precision of these comparisons cannot be assessed from the announcement alone.
The team also examined the role of weight loss. Differences remained statistically significant when the analysis focused only on participants who had lost weight, suggesting that weight loss alone may not explain the findings. Even so, this does not demonstrate a direct effect of the medications on the nails.
Hair and scalp symptoms
A companion study involving the same participants looked at hair and scalp symptoms, adding to growing interest in possible links between GLP-1 pathways and hair loss.
Unusual hair loss was reported by 50 per cent of people taking GLP-1 medications, compared with 34 per cent of controls. Reduced hair volume or density affected 42 per cent of people taking the medications, compared with 19 per cent of controls.
Among people taking the medications, hair loss was usually accompanied by scalp symptoms such as itching, redness or scaling.
Study author and dermatologist Bruno Halioua, from the Société Française des Sciences Humaines sur la Peau (SFSHP), suggests that this pattern could go beyond the hair shedding typically seen after rapid weight loss and may involve inflammation.
Because the hair findings came from the same group of people, they do not independently replicate the nail results. Instead, they offer another perspective on the symptoms reported within this sample. Whether similar patterns appear in other populations, and how often problems begin after treatment starts, remain questions for future research.
Important limitations to consider
The press release does not identify which GLP-1 medications participants were taking, nor does it provide results for any specific drug. The findings therefore cannot establish a nail effect linked to any single medication.
The release cites conference presentations as the sources for both studies and does not reference a published paper reporting them.
The nail study was conducted with institutional support from DUCRAY Laboratories, part of the Pierre Fabre Group, which develops dermatological and hair care products.
What comes next
The researchers now plan to follow patients from the start of their treatment. Standardised dermatological examinations and biological monitoring could help to establish when changes develop, what contributes to them, and whether they are reversible.
For healthcare professionals, findings like these highlight the value of asking about skin, hair and nail changes during routine reviews, and of recording any pre-existing problems before treatment begins. The College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme course is designed for clinicians who prescribe GLP-1 receptor agonists and support people throughout their treatment.
Advice for people noticing changes
Halioua describes the changes as frequent and usually benign. For people who notice nail changes, hair loss, or an itchy or red scalp, his advice is to discuss these symptoms with their doctor rather than stopping treatment themselves.
CCH insight
As GLP-1 receptor agonists become more widely used, people taking them are increasingly likely to raise questions about side effects, including changes to their nails, hair and skin. Feeling confident in discussing these concerns, recognising what may be linked to treatment, and encouraging people to continue the conversation rather than stop their medication are all key parts of good care.
Our GLP-1RA Therapy: The Complete Programme course helps healthcare professionals build the knowledge and confidence to prescribe and support people on GLP-1RA therapy safely and effectively.
Explore GLP-1RA Therapy: The Complete Programme →
Source: European Academy of Dermatology and Venereology (EADV) Congress 2026
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Do GLP-1s Slow Ageing Itself? A New Mouse Study Says They Might
Key Takeaways:
- In an NIH-funded study, semaglutide given to healthy 20-month-old mice improved muscle and cognitive function and reduced several molecular hallmarks of ageing.
- Mice treated until the end of life recorded a median lifespan almost 100 days longer than untreated mice.
- Against a 24% calorie-restricted diet, semaglutide matched most benefits, exceeded baseline in spatial memory and blood-sugar maintenance, and left metabolic rate largely unchanged.
A study that asks whether GLP-1s slow ageing itself
Research funded by the National Institutes of Health (NIH) has found that the GLP-1 receptor agonist semaglutide extended lifespan in older, healthy mice by tempering the detrimental effects of ageing. Investigators at the University of California, Berkeley went a step further than most work in this field by comparing the drug directly against reduced food intake. Semaglutide mimicked the anti-ageing benefits of calorie restriction and, in several respects, conferred even greater benefits.
The distinction matters. GLP-1 medicines have already been shown to delay the onset of a long list of age-related diseases in animals, and the clinical picture in people has broadened well beyond glycaemic control and weight. What this study adds is evidence gathered in healthy older animals, where no single disease is being treated. If the drug still produces benefit in that setting, the target may be ageing itself rather than any one condition downstream of it – a notion that could tie the widespread benefits of GLP-1s to a common source.
That framing is what makes the finding interesting to gerontologists as well as to those working in metabolic medicine.
“Most chronic diseases are deeply rooted in the aging process. If GLP-1 agonists do indeed slow it down, then a wide range of clinical benefits is exactly what you’d expect to see,” said Rafael de Cabo, Ph.D., a senior investigator at the NIH’s National Institute on Aging (NIA), and author of a commentary on the new study.
Treating late, when ageing is most pronounced
Many longevity experiments begin an intervention early and follow animals across most of their lives. The authors of this study, led by Danica Chen, Ph.D., took the opposite approach and started late, at the point where the effects of ageing are most pronounced. Semaglutide was administered to 20-month-old female mice for three months.
Set against a control group, the treated mice showed improved muscle function and improved cognitive function. Gene expression analysis pointed in the same direction at a molecular level: several hallmarks of natural ageing, including increased inflammation and reduced regenerative capacity, were reduced in the treated animals. In other words, the functional gains were accompanied by changes in the underlying biology rather than appearing in isolation.
A separate group of mice was treated until the end of life. Their median lifespan was nearly 100 days longer than that of untreated mice.
Separating the drug from the diet
Any intervention that reduces appetite invites an obvious question: is the benefit the drug, or simply the smaller portion? Because semaglutide reliably reduces food intake, the authors designed a head-to-head comparison to test whether its effects could be explained by eating less alone.
Over five months, one group of 20-month-old female mice received semaglutide, while another was placed on a 24% calorie-restricted diet matched to the feeding pattern of the treated animals. Matching the pattern, and not only the total, is what allows the two arms to be compared fairly.
The results drew numerous parallels between the two groups, with most physiological measurements remaining stable in both. Calorie restriction is a long-established intervention in ageing research, so this degree of overlap is itself a meaningful result for a pharmacological agent.
Where the two approaches diverged
Two differences stand out.
First, the semaglutide-treated mice surpassed baseline levels in exploratory behaviour, spatial memory and blood-sugar maintenance. These were not simply preserved measures, but measures that improved beyond where the animals started.
Second, the two groups differed in metabolic rate. It was reduced in the calorie-restricted animals, as would be expected when energy intake falls, but largely unchanged in the semaglutide-treated mice. A drug that delivers comparable benefits without the accompanying drop in metabolic rate is behaving differently from calorie restriction, not merely imitating it.
“These differences point to the possibility that GLP-1 drugs tap into a biological pathway independent of calorie restriction. Uncovering this potential route and the benefits that may specifically stem from it is an important direction for future research into the development of longevity-enhancing interventions,” said Chen, corresponding author of the study and professor of metabolic biology and nutrition at UC Berkeley.
What this does and does not mean for people
These findings may guide future research, but they do not imply that similar results could be achieved immediately in people. Mouse lifespan studies establish plausibility and direction, not clinical practice.
Additional clinical studies will be necessary to determine the clinical efficacy of GLP-1s on longevity in people, including work such as the recent post-hoc analysis of the SLIM LIVER trial. Chen also noted that future clinical investigations may explore benefits in healthy older individuals, which would greatly broaden the application of GLP-1s.
That last point is the one clinicians may want to watch. Prescribing at present is anchored to people living with obesity or type 2 diabetes and to defined clinical indications. A longevity indication in otherwise healthy older people would represent a different proposition altogether, with its own questions about risk, monitoring, muscle mass and long-term adherence.
Keeping pace with a fast-moving evidence base
For practitioners supporting people on GLP-1 therapies, the practical challenge is less about mouse longevity than about interpreting a rapidly expanding literature and explaining it accurately in consultations. Work of this kind is often reported as a longevity breakthrough, and people who have read those headlines may well raise it during appointments. The College of Contemporary Health’s CPD short course GLP-1RAs in Focus is designed for exactly that purpose, covering how GLP-1 receptor agonists work, what the current evidence does and does not support, and how to discuss benefits, limitations and expectations with the people in your care.
CCH insight
Although this study was conducted in mice, so cannot be directly extrapolated to humans, it clearly shows the GLP-1RAs must be acting through pathways other than those by which they induce weight loss. Considering the strong safety record of GLP-1RAs, it is surely now time to carry out trials on healthy, normal weight individuals to see if low-moderate doses can offer long-term benefits without negatively effecting body composition or other aspects of health.
Semaglutide’s effects in older mice sit at the edge of the current evidence base, but the questions they raise – about mechanism, about muscle and cognitive function, about how far the benefits of GLP-1s extend – are already reaching clinical conversations.
GLP-1RAs in Focus is a flexible, fully online CPD short course from The College of Contemporary Health, built for healthcare professionals who want a confident grounding in GLP-1 receptor agonists and the evolving research behind them.
Source: National Institutes of Health (NIH)
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