Scientists Identify the Biological Memory That Makes Obesity Relapse So Hard to Prevent
Key Takeaways:
- Researchers have identified a lasting biological change in fat cells – an “obesity memory” – that keeps the appetite-stimulating hormone asprosin elevated even after a person or animal has lost the excess weight.
- The same inflammatory signal can cross the placenta, programming a baby’s fat cells before birth and offering a molecular explanation for why obesity risk can pass from mother to child across generations.
- Blocking the asprosin pathway in mice prevented both weight regain after dieting and inherited obesity risk, suggesting a potential complementary target to use alongside or after GLP-1 receptor agonist treatment.
Two long-standing puzzles in obesity research
Two biological mysteries have resisted explanation for decades. The first is why almost everyone who loses weight eventually regains it, regardless of the method used to lose it. The second is why obesity is transmitted from mother to child at rates that diet and environment alone cannot account for. Scientists from the Harrington Discovery Institute at University Hospitals and Case Western Reserve University now believe they have identified the reason behind both.
In a study published in Cell Reports, the research team found that obesity produces a durable biological change within fat cells that keeps the hunger hormone asprosin elevated – a phenomenon the researchers describe as “obesity memory” – even once weight has been lost. The findings may help to explain why many people regain weight after dieting or after discontinuing GLP-1 medications, and why obesity risk can persist from one generation to the next.
An appetite signal stuck in the on position
“Imagine having an appetite-stimulating signal stuck in the ‘on’ position day after day, despite losing weight,” explained Atul Chopra, M.D., Ph.D., senior author of the study, investigator and associate director of the Harrington Rare Disease Program at Harrington Discovery Institute at UH, and associate professor of medicine, genetics and genomics at Case Western Reserve University School of Medicine.
“Our findings suggest one reason weight regain can be so difficult to prevent after treatment ends. This same signal can also cross the placenta from mother to baby. The result is a child born with a programmed susceptibility to obesity. This may also explain why obesity became an epidemic and why the cycle has continued for generations.”
The observation that weight regain and intergenerational risk are near-universal features of obesity is not new. What has been missing is the underlying molecular explanation.
“These patterns have been observed for decades, but nobody knew the exact molecular mechanism that makes obesity so persistent or how it transmits across generations,” Chopra added. “We wanted to find the biological basis for that persistence.”
A switch that stayed on
The team began the study by looking for what turns up production of the hunger hormone asprosin in obesity. They identified an inflammatory signal, TGF-β1, as the trigger. The most striking result was that only a brief exposure to that signal was required to create a lasting change, one that persisted for weeks after the signal itself had disappeared.
“It was like flipping a light switch that stays on even after you remove your finger,” Chopra said. “Even after mice lost all the excess weight and TGF-β1 returned to normal, this switch in their fat cells remained flipped, keeping asprosin and appetite elevated.
“This gives us a molecular explanation for why GLP-1 drugs, which suppress appetite while you take them, cannot fix the underlying biological memory that drives hunger back up once treatment ends. This same signal crosses the placenta and programs a baby’s fat cells before birth.”
In other words, the change in fat tissue is epigenetic rather than temporary. The cells retain a record of the obesity they were exposed to, and that record continues to drive hunger long after body weight has normalised.
What this means for GLP-1 therapy
The mechanism offers an explanation for a pattern already familiar to clinicians: people taking GLP-1 medications frequently regain weight once they discontinue treatment. The medication suppresses appetite for as long as it is taken, but it does not erase the epigenetic memory held in fat cells. When the pharmacological brake is released, the underlying appetite signal is still switched on.
This has practical implications for how GLP-1 therapy is planned, discussed and supported in practice, particularly around the point of discontinuation. Structured professional development in this area – such as the College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme short course – can help clinicians set realistic expectations with patients from the outset and plan for the period after treatment ends, rather than treating regain as an unexpected failure.
Pharmaceutical companies are actively searching for ways to help people maintain weight loss once treatment stops. The new findings identify a potential complementary target: a pathway that may sustain the biological drive towards regain after weight reduction.
Blocking asprosin changed the outcome
The researchers also tested what happened when the asprosin pathway was interrupted in mice, from the gene that produces the hormone through to the receptor in the brain that responds to it. Blocking this pathway prevented both weight regain after dieting and the inherited obesity risk passed to offspring.
That result points towards new therapeutic strategies aimed directly at the relapse problem that drug developers are currently trying to solve.
Evidence beyond a single laboratory
The study was deliberately designed to test its central observation outside the laboratory that made it. A separate laboratory led by Seth J. Field, M.D., Ph.D., independently reproduced the key persistence finding. Field is director of physician-scientist programs and chief scientific officer at the Harrington Discovery Institute at UH and a professor at Case Western Reserve School of Medicine.
Analyses of publicly available mouse and human datasets produced further supporting evidence. Additional human research is still needed, but the convergence across separate laboratories and independent datasets strengthens the case that this mechanism warrants serious investigation.
A message for clinicians
Chopra said the central message for clinicians is that obesity relapse is not a failure of willpower or discipline. It is driven by a durable biological memory written into fat tissue, which sustains hunger long after the weight has come off.
“We need to treat obesity as a condition that leaves lasting biological scars, not just a temporary state of excess weight,” he said.
Framing obesity in these terms has consequences for how conversations with patients are conducted. If regain reflects a persistent biological signal rather than a lapse in personal effort, then the clinical focus shifts towards long-term management and realistic planning for the period after active treatment.
Turning to human trials
The critical next step is translating these findings into people. The researchers plan to confirm that the same epigenetic memory operates in human fat tissue after weight loss, and to test whether therapies that block asprosin, or that reset these epigenetic marks, can prevent weight regain in people.
“Given the need for durable obesity treatments, we are interested in whether asprosin-blocking therapies could be used alongside or after GLP-1 treatment to prevent rebound,” Chopra concluded.
CCH insight
Research of this kind is changing how weight regain is understood and discussed in the consultation room. The College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme CPD short course is designed for healthcare professionals who prescribe or support people using GLP-1 receptor agonists, including the practical questions that arise around initiation, ongoing support and discontinuation.
Explore GLP-1RA Therapy: The Complete Programme →
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GLP-1 Prescribing in Under-12s Has Risen 310-Fold Since 2019
Key Takeaways:
- GLP-1 prescribing for US children aged 8 to 11 living with obesity rose 310-fold between 2019 and 2026, though overall numbers remain low.
- Most of those prescribed the medicines had severe obesity (93.7 per cent) and 65.2 per cent already had an obesity-related condition.
- Children in higher-income communities were 55 per cent more likely to receive a prescription, pointing to a widening access gap.
A first national picture of GLP-1 use in younger children
New research from NYU Langone Health has produced what its authors describe as the first national overview of how glucagon-like peptide-1 (GLP-1) receptor agonists are being prescribed to children under the age of 12 who are living with obesity in the United States.
The headline finding is one of rapid acceleration from a very low base. The number of US children under 12 living with obesity who were prescribed the weight loss medicines Saxenda, Wegovy and Zepbound remained low in June 2026 – but it was 310 times higher than in 2019, the year the medicines first began to be prescribed in this group.
The study was published online in the journal Pediatrics on 4 September.
What the researchers found
Among children aged 8 to 11 who were living with obesity and did not have diabetes, the proportion prescribed a GLP-1 receptor agonist increased from 0.03 per cent in 2019 to 9.3 per cent in 2026 – a 310-fold rise across a period of seven and a half years. Over that timeframe, 20,282 children aged 8 to 11 were prescribed a GLP-1 medicine.
The researchers also compared prescribing across age groups. GLP-1 medicines were less commonly prescribed to younger children living with obesity, aged 8 to 11, than to adolescents living with obesity, aged 12 to 17, at 0.6 per cent and 0.9 per cent respectively.
That age gradient persists even though clinical guidelines permit the use of these medicines for obesity in children from the age of 8. Girls were more likely than boys to receive a prescription.
An estimated 20 per cent of children in the US are living with obesity, defined as a body mass index (BMI) above the 95th percentile for children of the same age and sex, in the absence of diabetes – a well-recognised complication of the condition.
Who is being prescribed these medicines
The clinical profile of the children receiving GLP-1 medicines suggests that prescribers are, for the most part, reserving them for those with the greatest clinical need.
Most children prescribed a GLP-1 medicine had severe obesity (93.7 per cent), meaning their BMI was substantially higher than that of almost all other children of the same age and gender. Most (65.2 per cent) were also living with at least one illness linked to obesity, such as raised cholesterol, high blood pressure or sleep apnoea.
A further quarter of the younger children living with obesity who were prescribed GLP-1s had prediabetes, placing them at high risk of developing the condition most commonly associated with obesity.
Why the researchers see this as a valuable tool
Lead investigator and obesity medicine specialist Babak J. Orandi, MD, PhD, an associate professor in the Departments of Surgery and Medicine at NYU Grossman School of Medicine, framed the findings as both a snapshot and a signal.
“Our study offers the first national overview in young children of the use of GLP-1 drugs to fight the obesity epidemic in the United States and shows that while the absolute numbers of children under the age of 12 receiving GLP-1 treatment is still low, GLP-1 use is accelerating rapidly,” said Dr Orandi. “The careful use of GLP-1s remains a valuable tool in confronting the obesity epidemic among young Americans.”
Dr Orandi noted that GLP-1 medicines can be highly effective in treating obesity and improving its metabolic complications, supporting weight loss, better blood sugar regulation and appetite suppression.
Weighing the risks of treating and of not treating
The study team was explicit that the decision facing families is not a simple choice between risk and safety.
While parents may hesitate at the prospect of their child being prescribed one of these medicines, there are also long-term risks attached to withholding treatment from young children living with obesity. Those risks include the development of chronic conditions such as diabetes, high blood pressure and liver disease in early adulthood and middle age.
For clinicians supporting families through exactly this kind of conversation, the College of Contemporary Health’s CPD short course GLP-1RAs in Practice (Prescribing and Supporting) addresses the practical side of initiating and monitoring GLP-1 therapy, including how to discuss benefits, risks and expectations with patients and their families.
An emerging gap in access
Alongside the prescribing trend itself, the study surfaced a socioeconomic pattern that the authors treat as a warning sign.
Many young children living with obesity in upper-income communities were 55 per cent more likely to be prescribed GLP-1 medicines than those who were not.
Study co-senior author Allan B. Massie, PhD, an associate professor in the Departments of Surgery and Population Health at NYU Grossman School of Medicine, said that current prescribing patterns already show the beginnings of a growing divergence between those who do and those who do not have access to the medicines.
“Physicians and health policymakers alike have a responsibility to ensure, as use of GLP-1 medications continues to rise, that all young children with obesity who need these drugs have access to them and that these valuable and sometimes costly treatments become available to more than those who have access to health insurance and can afford to visit pediatric clinics,” said Dr Massie.
The case for long-term monitoring
Dr Orandi said that long-term monitoring of children prescribed GLP-1 medicines is needed to confirm that the drugs remain both safe and effective in this age group.
Clinical trials are already under way in children living with obesity from as young as 6 years of age. Dr Orandi said these will inform and offer guidance to physicians, policymakers and parents as the use of anti-obesity medicines continues to grow.
How the study was carried out
The team drew on Epic Cosmos, a national dataset built from the electronic health records of more than 300 million American patients. The dataset covers 2,067 hospitals and 47,100 health clinics that use Epic, the largest electronic health record vendor in the US. Epic had no role in conducting the study.
Funding, authorship and disclosures
Funding support for the study was provided by NYU Langone.
Alongside Dr Orandi and Dr Massie, the NYU Langone researchers involved as co-investigators were Suhani S. Patel, MPH; Mary Jo Messito, MD; Michal A. Mankowski, PhD; and Dorry L. Segev, MD, PhD.
Dr Orandi has served on an advisory board for the pharmaceutical company Boehringer Ingelheim. Dr Segev has received consulting and speaking honoraria from Sanofi, CareDx, Moderna, AstraZeneca, Roche, Optum, OrganOx, Hansa Biopharma and Biosidus, and is a journal editor for Springer. None of these activities relate to the current Pediatrics study. NYU Langone is managing the terms and conditions of these relationships in line with its policies and procedures.
What this means for practice
The picture emerging from this study is of a treatment moving quickly from the margins towards the mainstream in a younger age group than many clinicians and families may expect – and doing so unevenly. Prescribing appears to be concentrated among children with the highest clinical need, but also among those with the greatest access to care.
For healthcare professionals, that combination raises practical questions about assessment, shared decision-making with families, monitoring over long periods, and equity of access within their own services.
CCH insight
Supporting children and families through GLP-1 therapy calls for confidence in both the pharmacology and the conversation. The College of Contemporary Health’s CPD short course GLP-1RA Therapy: The Complete Programme is designed for healthcare professionals who want a structured, evidence-based grounding in initiating, monitoring and supporting GLP-1 receptor agonist treatment – including how to set realistic expectations and manage long-term follow-up.
Explore GLP-1RA Therapy: The Complete Programme →
Source: NYU Langone Health
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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
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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GLP-1 Receptor Agonists: The Emerging Case for Microdosing
Key Takeaways:
- A narrative review in Cureus finds that the benefits of GLP-1 receptor agonists (GLP-1RAs) extend beyond weight reduction to cardiovascular, renal, metabolic and other outcomes.
- Its authors propose microdosing – smaller, fractional doses – as a tolerability-first approach for people who respond strongly to standard doses or who struggle with gastrointestinal side effects.
- Direct evidence is extremely limited, and microdosing remains off-label, so the authors advise caution and clinician guidance.
Why a tolerability-first conversation is gaining ground
In a recent non-systematic narrative review published in the journal Cureus, researchers summarised the current evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and discussed the possible benefits of microdosing these agents. Their central question is a practical one that clinicians increasingly face in consultation rooms: if the multisystem benefits of this drug class are real, can smaller doses preserve enough of them to keep people in treatment?
Obesity remains a substantial health concern
Obesity continues to represent a significant health concern worldwide. In the United States (US), the prevalence of generalised obesity among adults, defined as a body mass index (BMI) above 30 kg/m², and of extreme obesity, defined as a BMI above 40 kg/m², has been increasing. Childhood obesity, by contrast, is defined using age- and sex-specific BMI thresholds rather than a single fixed cut-off.
Data from a survey conducted between 2021 and 2023 indicate that 21% of children and adolescents and 40% of adults in the US were living with obesity. Those figures give a sense of the scale of the population for whom pharmacological options are now being considered, and of the pressure placed on services that support people with obesity and related conditions.
From exenatide to semaglutide: a rapidly expanding drug class
The development of GLP-1RAs has been a remarkable advancement in the treatment of obesity and diabetes. Exenatide was the first GLP-1RA approved for type 2 diabetes in 2005, and the class has since expanded to include liraglutide, dulaglutide and semaglutide.
Success, however, has brought its own difficulties. Demand for GLP-1RAs far exceeds supply, and this imbalance has contributed to high costs and significant gaps in care. The authors suggest that these pressures have encouraged greater use of medication microdosing, as people and their clinicians look for ways to stretch limited or expensive supplies of medication further.
What microdosing means in this context
The term microdosing has a specific technical origin. It originally referred to sub-pharmacologically active doses used in drug-development studies, where the intention was never therapeutic effect. The review deliberately uses the term in a different, clinical sense: smaller, fractional doses of a medication that may allow people to receive some therapeutic benefit while extending their use of the medication.
That distinction matters when interpreting the literature, because the pharmacokinetic and the clinical uses of the word describe quite different practices. It is the second, clinical meaning that the review sets out to examine.
Clinical benefits of GLP-1 receptor agonists
GLP-1RAs modulate energy intake and promote satiety through agonism of the GLP-1 receptor. They also improve glycaemic control by suppressing glucagon and stimulating insulin secretion. These two mechanisms account for much of the drug class’s original appeal in both diabetes and obesity care.
A recent umbrella review noted trends towards improvements in respiratory, renal, metabolic, endocrine and cardiovascular outcomes, as well as cognitive function, with GLP-1RAs. Taken together, these findings suggest that the benefits of the drug class may extend beyond weight reduction across multiple organ systems, which is precisely why the question of preserving those benefits at lower doses has become interesting.
Cardiovascular and renal outcomes
A meta-analysis reported that GLP-1RAs led to significant reductions in major adverse cardiovascular events (MACE) and mortality. A further meta-analysis showed that long-acting GLP-1RAs reduced MACE and improved a composite kidney outcome among people with type 2 diabetes.
An umbrella review similarly reported that GLP-1RAs were associated with improvements in body weight, glycaemic control and various renal and cardiovascular outcomes. Importantly, the certainty of evidence was lower for some of the cardiovascular and kidney outcomes, so these associations should not all be read with equal confidence.
Emerging and early-stage evidence
Beyond the established indications, the review points to areas where evidence is still at a very early stage. A case report described a 34-year-old woman with type 2, stage III lipoedema who showed improvements after 30 days of treatment with low-dose tirzepatide, a dual GIP and GLP-1 receptor agonist. A single case, however, cannot establish treatment efficacy.
A systematic review indicated that GLP-1RAs significantly improved one measure of motor function among people with Parkinson’s disease. Other motor outcomes did not improve significantly, and adverse events were more frequent. This is a useful reminder that a positive signal on one outcome measure does not amount to a demonstrated clinical benefit overall.
Current dosing regimens of GLP-1RAs
Gradual dose titration is recommended for GLP-1RAs such as liraglutide and semaglutide in order to reduce the risk of adverse gastrointestinal (GI) effects.
For obesity, semaglutide is initiated at 0.25 mg once weekly for four weeks, then increased to 0.5 mg, 1 mg and 1.7 mg once weekly for four weeks each, until reaching 2.4 mg after 16 weeks. Liraglutide, by contrast, is initiated at 0.6 mg daily for the first week, then 1.2 mg daily, 1.8 mg daily and 2.4 mg daily for one week each, reaching 3 mg daily after four weeks.
For diabetes treatment, semaglutide and liraglutide can be dosed up to 2 mg and 1.8 mg respectively, as weekly and daily subcutaneous injections. Tirzepatide has identical dosing for both type 2 diabetes and obesity: treatment starts at 2.5 mg once weekly, increases to 5 mg once weekly four weeks later, and then rises in further 2.5 mg increments every four weeks to a maximum of 15 mg weekly.
The logic of these schedules is worth noting. Titration exists because tolerability, rather than efficacy alone, governs how quickly a person can reach a therapeutic dose. Fractional dosing takes that same logic and extends it further down the dose range. Understanding titration, tolerability and shared decision-making in enough depth to have these conversations well is now core to obesity and diabetes practice, and it forms the focus of the College of Contemporary Health’s CPD short course GLP-1RA Therapy: The Complete Programme.
Tolerability and the case for microdosing
The primary limitation of long-term GLP-1RA use is adverse GI effects, including nausea, diarrhoea, constipation and vomiting. These are also among the leading causes of treatment discontinuation, which means that tolerability is not a secondary concern but a direct determinant of whether anyone benefits from treatment at all.
More severe adverse effects, including intestinal obstruction, delayed gastric emptying and biliary disease, have been variably reported, with inconsistent evidence regarding these complications. Notably, tolerability has often been found to improve over time, which suggests that fractional or lower dosing may support treatment continuity.
Microdosing as a tolerability-first framework
The authors propose microdosing as a tolerability-first framework, enabling clinicians to personalise dosing to the individual and potentially reduce barriers to treatment. They suggest it could be a valuable option for people who have exaggerated pharmacological responses to a standard dose, and for those who are highly sensitive to adverse effects.
Two important caveats accompany the proposal. First, studies on the effects of microdosing GLP-1RAs are extremely limited. Second, the established benefits of standard GLP-1RA doses cannot be assumed to persist with fractional dosing. Dose-escalation trials do suggest a strong therapeutic response in some people at submaximal doses, which is part of what makes the idea plausible, but plausibility is not proof.
What the evidence on lower doses currently shows
A prospective observational study found improvements in body weight, BMI, triglycerides, glycated haemoglobin and low-density lipoprotein cholesterol with low-dose tirzepatide among non-diabetic adults with obesity.
In addition, a pooled analysis of phase III trials assessing once-weekly semaglutide doses of 0.5 mg and 1 mg indicated improved tolerability over time and reduced sensitivity to adverse GI events with long-term exposure.
Both findings are encouraging, but the review is clear about their status: these studies provide indirect support rather than direct evidence from trials specifically designed to test a microdosing strategy.
Practical and safety considerations
The review also notes two constraints that clinicians need to weigh before considering this approach. Microdosing is an off-label approach, and fractional dosing using existing injection devices may raise sterility and safety considerations. The authors therefore recommend caution and clinician guidance before anyone begins a microdosing regimen.
Concluding remarks
Collectively, although microdosing emerged as a pharmacokinetic tool in drug development, the authors describe it as an emerging pragmatic approach in clinical practice. Alongside other treatment modalities, it may better support people in reaching their health goals and improve their quality of life.
The honest conclusion, however, is that there is limited direct evidence on microdosing GLP-1RAs. Further research is warranted to confirm whether fractional dosing helps maintain the long-term benefits that have been demonstrated at standard doses. For now, the concept is best understood as a personalised, tolerability-led hypothesis worth studying rather than a settled standard of care.
CCH insight
Conversations about titration, tolerability and dose personalisation are becoming a routine part of obesity and diabetes care, and they demand a confident grasp of both the pharmacology and the person in front of you.
The College of Contemporary Health’s CPD short course GLP-1RA Therapy: The Complete Programme is designed for healthcare professionals who want to build exactly that confidence, covering how these medicines work, how they are dosed and titrated, how adverse effects are anticipated and managed, and how to support people effectively throughout treatment.
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GLP-1 Medications May Reshape Obesity Care, but Clinicians Still Have Questions
Key Takeaways:
- Staff saw injectable GLP-1 medications as a valuable middle option between behavioural support and bariatric surgery.
- Their strongest concerns centred on what happens after treatment stops, particularly weight regain and masked behavioural patterns.
- Most had learned about these medications from patients rather than through formal training.
A service preparing for a change it had not yet made
A qualitative study published in Obesity Science & Practice set out to capture something rarely documented: what healthcare professionals think about injectable GLP-1 medications before their service begins prescribing them. The researchers interviewed staff at a United Kingdom Tier 3 weight management service that had applications for approval in place but was not yet prescribing, giving an unusually clean view of expectations, hopes and anxieties uncoloured by direct prescribing experience.
The timing matters because these medications are moving quickly into routine obesity care. One in eight people worldwide lives with obesity, a scale that demands sustained attention from health authorities. In England, weight management is organised across four tiers, running from population-level prevention and lifestyle services through to specialist multidisciplinary care and bariatric surgery. Injectable GLP-1 medications, including semaglutide and tirzepatide (a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist), are increasingly built into these pathways. Semaglutide is recommended for eligible patients within specialist services, while tirzepatide can also be prescribed in NHS primary care.
How the study was carried out
Participants were recruited from a Tier 3 service in England providing interpersonal nutritional advice and behavioural support to people with a body mass index above 40 kg/m², or between 35 and 39.9 kg/m² alongside a weight-related comorbidity.
Interviews took place between 20 June and 19 July 2024. Eligible participants were behavioural change advisors or nutrition advisors, and importantly, none of them held prescribing privileges. Staff were invited by email and completed an information sheet, an electronic consent form, a demographic questionnaire and an interview-date selection.
The research team developed a semi-structured interview schedule, refining it after a pilot interview. Questions covered knowledge of semaglutide, perceived benefits, concerns, possible psychological consequences, long-term outcomes, service integration and information needs. Interviews were audio-recorded and transcribed verbatim, then analysed using Braun and Clarke’s six-stage reflexive thematic analysis. Transcripts were read repeatedly and coded in NVivo 14, with preliminary themes developed, discussed, revised, mapped, defined and named. Analysis was predominantly inductive, with a deductive element used to group themes according to the research questions, and the dataset was interpreted through a constructivist lens.
The recruitment email reached 17 healthcare professionals. Thirteen expressed interest and 11 completed interviews, comprising six nutrition advisors and five behavioural change advisors. Interviews ran from 34 to 62 minutes, with a mean of 46 minutes. Sample size was guided by information power rather than a fixed target. Thirteen themes emerged, organised into four clusters: knowledge and information needs, perceived benefits, concerns, and service provision considerations.
Learning from patients rather than from training
One of the more striking findings concerns where knowledge was coming from. Participants had mainly learned about injectable GLP-1 medications through patients who had purchased them privately. Most did not feel confident in their current understanding, reported little formal training, and often sought out information independently, though lack of time limited how far they could go.
That said, the baseline was not zero. All participants knew the medications could facilitate weight loss, and most recognised appetite suppression as an important mechanism, although understanding of how the drugs work varied considerably. A few had deeper knowledge of semaglutide’s physiological effects. Gastrointestinal effects were widely mentioned, including nausea, constipation and diarrhoea.
It is a gap that structured continuing professional development is well placed to close. CCH’s GLP-1RAs in Focus short course was built for professionals in exactly this position, including non-prescribers supporting people on GLP-1RA pathways who want a working grasp of the underlying physiology and pharmacology rather than a patchwork assembled from patient conversations.
Seen as a middle path, not a shortcut
Most participants held positive views and regarded injectable GLP-1 medications as a useful weight-loss tool. Several felt that early weight loss could boost patients’ confidence in their own ability to lose weight, and in turn encourage greater engagement with behavioural support.
Many framed the medications as a valuable middle ground between behavioural support and bariatric surgery, particularly for people with complex needs or those who did not want surgery. At the same time, participants were clear that the drugs were not a substitute for a patient’s own efforts. Where lifestyle change alone was achievable, it was generally the preferred route, partly because it could help people feel more in control of their own progress.
Concerns clustered around what happens next
The dominant concern was not the treatment period itself but what follows it. Most participants worried about weight regain after discontinuation, particularly where behavioural changes had not become established during treatment.
Closely linked to this was a worry about masking. Participants feared that appetite suppression could obscure emotional eating, stress eating, unhelpful habits and other behavioural patterns, making it harder to tell which changes were driven by the medication and which by behavioural support. There was also concern that successful weight loss could create a false sense of security, reduce engagement with lifestyle advice, or foster reliance on medication.
Some participants raised possible mental health risks, including disordered eating or worsening difficulties among people with eating disorders, psychological trauma or a history of self-harm. It is worth being precise here: these were concerns held by participants rather than harms they had observed, and the authors noted that current evidence does not support a causal relationship between GLP-1 medications and suicidal or self-injurious thoughts or actions.
Where behavioural support should sit in the pathway
Many participants favoured offering behavioural and lifestyle support before prescribing begins, giving time to understand individual needs and to manage expectations about what the medication can and cannot do. Almost all supported providing that help alongside treatment, though views differed on how often and for how long.
Some also argued for support during dose reduction and for a few months after treatment ends, precisely because of the regain risk they had identified. The introduction of GLP-1 prescribing into their own service was viewed by some as experimental and as a learning process, and participants anticipated that their professional roles and responsibilities would shift as a result.
What this study cannot tell us
The authors were candid about the limits. The study included 11 professionals from a single Tier 3 service that had not yet started prescribing injectable GLP-1 medications, so the findings may not generalise to other services or to professionals with direct prescribing experience. The interviewer also worked within the same service, which may have shaped how freely participants expressed their views.
What it means for practice
Taken together, the picture is of a workforce that is broadly positive about injectable GLP-1 medications and sees a clear clinical niche for them, but that is thinking hard about continuity of care. The concerns raised, weight regain after discontinuation, reduced engagement with behavioural support, masked behavioural patterns and possible mental health risks, are perceived rather than demonstrated harms, but they point to real design questions for services.
The authors conclude that further research is needed on combining injectable GLP-1 medications with interpersonal behavioural support, and on how that integration can best sustain patients over time. In the meantime, the most actionable finding may be the simplest one: the staff closest to patients wanted better information and had few structured routes to get it.
CCH insight
This study lands on something many services will recognise: the staff supporting people on GLP-1RA pathways are often the least formally trained in how these medications work, and the anxiety sits not in the prescription itself but in the months that follow it.
GLP-1RA Therapy: The Complete Programme (Ozempic, Wegovy & Mounjaro) is built around that full sequence, covering the science, safe prescribing and the long-term care that protects the result, from nutrition and lean mass through to plateaus and when to refer. Seven CPD hours, three Certificates of Completion, and the CCH Advanced Certificate in GLP-1RA Therapy on passing the capstone. Open to prescribers and non-prescribers alike.
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Novo Nordisk Launches Late-Stage Trial to Find the Lowest Effective Dose of Oral Wegovy
Key Takeaways:
- Novo Nordisk has begun OASIS-5, a 60-week late-stage trial testing lower maintenance doses of the oral Wegovy pill.
- The trial will enrol 450 adults with a BMI of 30 or above, or 27 with a weight-related health condition.
- Interest in lower dosing reflects real-world practice, where cost and side effects already drive some people to take reduced doses.
A trial built around dose flexibility
Danish drugmaker Novo Nordisk has started testing smaller doses of its Wegovy pill in a new late-stage study designed to identify the lowest dose that still supports weight loss, according to a listing on a US clinical trials database.
The study, known as OASIS-5, began on 12 August and is scheduled to run until 2028. It will examine lower strengths of the daily maintenance dose – the dose used to sustain weight loss once it has been achieved, rather than the escalating doses used at the start of treatment. At present, the approved long-term dose of the Wegovy pill is 25 milligrams.
“Having a broader range of maintenance doses could provide greater flexibility in treatment and optimising the patient experience,” Novo said in an emailed statement to Reuters.
Novo has not specified which new dose strengths are being tested. The Wegovy pill is also approved in doses of 1.5 mg, 4 mg and 9 mg.
What OASIS-5 will measure
The 60-week trial will recruit 450 adult participants who have previously struggled to lose weight, with a Body Mass Index of 30 or above, or 27 in combination with a weight-related health issue.
The primary objective is to establish whether lower doses of oral semaglutide – the active ingredient in Wegovy – produce greater weight loss than placebo over the 60-week period. Secondary objectives include changes in waist circumference, other health benefits and the side effect profile at these reduced strengths.
The study will exclude people living with diabetes, those who have experienced recent major weight changes, and anyone currently being treated with GLP-1 medications.
Seeking health benefits beyond weight loss
The trial arrives against a backdrop of dosing behaviour that is already happening outside clinical protocols. Some people taking GLP-1 medicines, including Wegovy and Lilly’s Zepbound injections, are microdosing or otherwise taking lower-than-approved doses. The practice has become popular largely because of the high cost of the medicines and the side effects associated with them.
“People are using low dosages of these products… they just decide on their own,” Novo CEO Mike Doustdar told Reuters in an interview last week, noting that patients often seek health benefits beyond weight loss.
That observation points to a broader question facing prescribers: what people hope to gain from GLP-1 therapy is not always confined to the number on the scales. Understanding the pharmacology behind dose escalation and maintenance, and being able to discuss the trade-offs between efficacy, tolerability and cost, is increasingly central to safe prescribing. It is a theme covered directly in the College of Contemporary Health’s CPD short course GLP-1RAs in Practice: Prescribing, which examines dose titration, monitoring and shared decision-making in day-to-day clinical settings.
Competitive pressure in a growing market
Novo is under pressure after losing ground to US rival Eli Lilly in an obesity drug market projected to exceed $100 billion by 2030. Investors are watching the Wegovy pill closely; it generated second-quarter sales of 3.22 billion Danish kroner ($499.89 million).
Doustdar expects market segmentation to prevent a winner-take-all contest with Lilly – a view consistent with a future in which different doses, formulations and treatment goals serve different groups of people rather than a single product dominating.
Lilly did not immediately respond to a Reuters request for comment on whether it plans to test smaller doses of its oral drug Foundayo, which has lowest approved doses of 0.8 mg and 2.5 mg.
What this could mean for practice
If OASIS-5 demonstrates that lower maintenance doses deliver meaningful weight loss, it would give clinicians a wider set of options for people who cannot tolerate higher strengths, who are managing the cost of long-term therapy, or who have reached a weight they wish to maintain rather than continue reducing. It would also bring an existing real-world practice within the evidence base, replacing self-directed dose reduction with an approved, monitored alternative.
Results are not expected until 2028, so any change to prescribing practice remains some way off. In the meantime, conversations about dosing, expectations and adherence will continue to sit with the healthcare professionals supporting people through treatment.
CCH insight
Dose selection, titration and tolerability are among the most common practical challenges in GLP-1 prescribing. The College of Contemporary Health’s CPD short course GLP-1RAs in Practice: Prescribing covers dose escalation and maintenance, managing side effects, patient selection and monitoring – equipping healthcare professionals to make confident, evidence-based decisions as the treatment landscape evolves.
Explore GLP-1RAs in Practice: Prescribing →
Source: Reuters
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Stanford Scientists Use AI to Discover a “Natural Ozempic” Free of the Usual Side Effects
Key Takeaways:
- Stanford Medicine researchers used a purpose-built AI algorithm to identify BRP, a 12-amino-acid peptide that reduced food intake in mice and minipigs.
- BRP appears to act specifically in the hypothalamus, and in animal testing did not produce the nausea, constipation or major muscle loss linked to semaglutide.
- The findings remain preclinical, with receptor identification and peptide durability still to be resolved before human trials can begin.
A naturally occurring molecule with semaglutide-like effects
Researchers at Stanford Medicine have identified a naturally occurring molecule that may suppress appetite and reduce body weight in a manner resembling semaglutide, the active ingredient in Ozempic. In animal studies, the molecule also appeared to sidestep several of the problems associated with the drug, including nausea, constipation and substantial muscle loss.
The molecule, known as BRP, works through a different but related metabolic pathway and activates a separate group of neurons in the brain. That distinction could make it a more precise tool for controlling appetite and body weight.
Why a hypothalamus-focused signal matters
The appeal of BRP lies in where it appears to act. Semaglutide’s receptor targets are distributed widely across the body, which helps explain the breadth of its effects – and the breadth of its unwanted ones.
“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,” said assistant professor of pathology Katrin Svensson, PhD. “That’s why Ozempic has widespread effects including slowing the movement of food through the digestive tract and lowering blood sugar levels. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
The hypothalamus is a small region deep within the brain that helps regulate hunger, body temperature, hormone activity and energy use. Because BRP appears to act mainly in this area, it may influence appetite without producing as many effects elsewhere in the body.
Svensson has co-founded a company that plans to begin clinical trials of the molecule in humans in the near future.
Svensson is the senior author of the research, which was published on 5 March in Nature. Senior research scientist Laetitia Coassolo, PhD, is the lead author of the study.
Hunting for hidden peptides with artificial intelligence
The discovery depended heavily on artificial intelligence, which allowed the researchers to search through proteins belonging to a group known as prohormones.
Prohormones are inactive precursor molecules. They do not perform their final biological function until enzymes cut them into smaller fragments called peptides. Some of these peptides then act as hormones, carrying signals that influence metabolism, appetite and other complex processes in the brain and throughout the body.
A single prohormone can be cut in several different ways, producing many possible peptides. Finding the biologically important ones is difficult, because genuine peptide hormones are relatively rare and can be buried among large numbers of ordinary fragments created during normal protein processing and breakdown.
Traditional laboratory methods can isolate and identify peptides, but the process can generate enormous quantities of data. Researchers may need to sort through hundreds of thousands of molecules to find the few that have meaningful effects.
Narrowing the search to prohormone convertase 1/3
The team concentrated on an enzyme called prohormone convertase 1/3. This enzyme cuts prohormones at specific amino acid sequences and has previously been linked to obesity in humans.
One of the peptides produced through this process is glucagon-like peptide 1, or GLP-1. GLP-1 helps regulate hunger and blood sugar, and semaglutide works by copying its effects in the body.
The researchers reasoned that the same enzyme might produce other peptides that influence energy balance and appetite. To find them, they turned to artificial intelligence.
Peptide Predictor: from 20,000 genes to 373 prohormones
Rather than manually extracting proteins and peptides from tissues and then using methods such as mass spectrometry to identify huge numbers of molecules, the researchers created a computer algorithm called Peptide Predictor.
The program searched all 20,000 human protein-coding genes for the types of sites where prohormone convertases typically cut proteins. The researchers then narrowed the search to genes that produce proteins secreted outside the cell – a common feature of hormones – and that contained at least four possible cleavage sites.
That process reduced the field to 373 prohormones, giving the team a far more manageable group to investigate.
“The algorithm was absolutely key to our findings,” Svensson said.
Peptide Predictor estimated that prohormone convertase 1/3 could produce 2,683 distinct peptides from those 373 proteins. Coassolo and Svensson then focused on the sequences that seemed most likely to affect the brain.
They selected 100 peptides, including GLP-1, and tested whether they could stimulate neuron-like cells grown in the laboratory.
A 12-amino-acid peptide with an outsized effect
As expected, GLP-1 strongly activated the neuronal cells, increasing their activity to three times the level seen in untreated control cells.
One much smaller peptide produced an even more dramatic response. Made from only 12 amino acids, it increased neuronal activity tenfold compared with controls.
The researchers named the peptide BRP after its parent prohormone, BPM/retinoic acid inducible neural specific 2, or BRINP2 (BRINP2-related-peptide).
Amino acids are the basic building blocks of proteins and peptides. A molecule containing only 12 of them is extremely small compared with most full-sized proteins, yet BRP produced the strongest response in the initial cell tests.
Food intake fell by up to 50 per cent
The researchers next tested BRP in lean mice and in minipigs, which more closely mirror human metabolism and eating patterns than mice do.
An intramuscular injection given before feeding reduced food intake during the following hour by as much as 50 per cent in both species.
The team also gave daily BRP injections to mice with obesity for 14 days. On average, the treated animals lost 3 grams, with nearly all of the reduction coming from body fat. Animals in the control group gained about 3 grams over the same period.
The treated animals also showed improved glucose and insulin tolerance. These measures reflect how effectively the body regulates blood sugar and responds to insulin, the hormone that helps move glucose from the bloodstream into cells.
Because incretin-based therapies are now a routine part of weight management for many people living with obesity, clinicians looking to keep pace with the underlying pharmacology and with structured patient support pathways increasingly turn to focused CPD such as the College of Contemporary Health’s GLP-1RA Complete Programme.
No clear signs of the usual side effects
Behavioural testing found no meaningful differences between treated and untreated animals in movement, water consumption, anxiety-like behaviour or faecal output.
The absence of changes in faecal output was especially notable, because semaglutide can slow digestion and cause constipation. The researchers also did not observe the nausea-related responses or major muscle loss associated with some existing weight loss treatments.
Additional measurements of brain activity and body function showed that BRP acts through metabolic and neuronal pathways that differ from those activated by GLP-1 or semaglutide.
Those findings suggest that BRP may reduce appetite through a more focused biological route, although the results remain limited to animals.
What still needs answering before human testing
The researchers are now working to identify the cell-surface receptors that attach to BRP. Receptors are molecular structures that receive signals from hormones, drugs and other chemical messengers. Determining which receptor BRP uses will help scientists understand exactly how the peptide changes appetite and metabolism.
The team also wants to map the full sequence of events that occurs after BRP binds to its target.
Another challenge is duration. Small peptides are often broken down quickly in the body, which can shorten their effects. The researchers are investigating ways to make BRP last longer so that, if it eventually works in people, it could be administered on a more practical schedule.
“The lack of effective drugs to treat obesity in humans has been a problem for decades,” Svensson said. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if it is safe and effective in humans.”
CCH insight
Discoveries like BRP sit at the frontier of a field that is already reshaping day-to-day practice. For healthcare professionals supporting people living with obesity, a working command of GLP-1 receptor agonist pharmacology, patient selection, side-effect management and long-term follow-up is now core knowledge rather than a specialism.
The College of Contemporary Health’s GLP-1RA Complete Programme brings this together across three courses and a capstone, leading to an Advanced Certificate, with seven CPD hours and seven downloadable clinical tools designed for use in practice.
Explore the GLP-1RA Complete Programme →
Source: Stanford Medicine
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Surgery Plus Medication Outperforms Surgery Alone in Young People
Key Takeaways:
- Young people who restarted obesity medication a median of one month after sleeve gastrectomy lost more weight at 12 months than those who had surgery alone.
- Improvements in eating behaviours, including hunger scores, were significantly greater in the early reinitiation group.
- Rates of postoperative complications, readmissions, emergency department visits and reoperations did not differ between the two groups.
Combining pharmacotherapy with surgery in adolescent obesity care
Restarting obesity medication, including glucagon-like peptide-1 (GLP-1) receptor agonists, shortly after sleeve gastrectomy is associated with greater weight loss at one year than surgery alone in adolescents, according to a research letter published online on 22 July in JAMA Surgery.
The finding speaks to a question that has become increasingly pressing as both metabolic and bariatric surgery and highly effective obesity pharmacotherapy have become available to younger patients: whether the two should be sequenced, or used together.
What the researchers set out to examine
Dr Alaina P. Vidmar, of Children’s Hospital Los Angeles, and colleagues evaluated the 12-month safety, weight trajectory and eating behaviour outcomes associated with early reinitiation of obesity medication following metabolic and bariatric surgery.
The analysis included 99 young people aged 7–20 who underwent sleeve gastrectomy between November 2023 and February 2026.
Half the cohort restarted medication within a month of surgery
Of the 99 young people in the cohort, 53 reinitiated obesity medication, with a median time to reinitiation of 1.0 month.
Among those who restarted treatment, most resumed the same class of medication they had been prescribed before surgery. Postoperative regimens were nonetheless generally consolidated, with fewer young people requiring multiagent therapy after their operation than before it.
Weight trajectories diverged after the six-month mark
Through the first six months, the two groups experienced similar early postoperative weight loss.
The picture changed by the end of the first year. The early reinitiation group achieved a greater mean reduction in body mass index (BMI) percentage at 12 months than the group who had surgery alone, at −29.3% versus −25.5%. The same pattern held for excess BMI loss percentage, at −53.6% versus −45.7%.
Eating behaviours improved more with combined treatment
Improvements in eating behaviours were significantly greater in the early reinitiation group at 12 months than in the surgery-only group. Median hunger scores on the Adult Eating Behaviour Questionnaire, for example, fell by 3.5 points in the early reinitiation group, compared with a rise of 0.2 points among those treated with surgery alone.
This behavioural dimension is a reminder that appetite regulation after surgery is not a fixed quantity, and that the interaction between pharmacological and surgical mechanisms is an area where prescribing clinicians increasingly need structured, up-to-date grounding. The College of Contemporary Health addresses precisely this territory in its GLP-1RA Complete Programme, which covers the pharmacology, patient selection, monitoring and behavioural support that underpin safe long-term use of these agents.
Safety outcomes were comparable between the groups
There was no difference between the groups in postoperative complications, including biliary events requiring cholecystectomy, readmissions, emergency department visits and reoperations.
A lifespan view of severe obesity
The authors frame the results as support for treating severe obesity in young people as a chronic condition requiring more than one modality.
“Bariatric surgery is the most durable and effective treatment for severe obesity, but for youth with severe disease, we need a multimodal approach, which means combining medication and surgery over the lifespan,” Vidmar said in a statement.
CCH insight
For clinicians supporting young people through and beyond metabolic and bariatric surgery, findings like these shift the practical question from whether to prescribe to when, what and for how long. Confidence with GLP-1 receptor agonists, and with the behavioural and monitoring work that surrounds them, is becoming a core competency rather than a specialist interest.
The College of Contemporary Health’s GLP-1RA Complete Programme is designed for healthcare professionals who want that grounding: mechanisms of action and the wider incretin landscape, patient selection and contraindications, dose escalation and adverse effect management, and the behaviour change support that helps people sustain outcomes over time. It is CPD-accredited and studied entirely online, so it fits around clinical commitments.
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Obesity Medication Significantly Reduces Risk of Infections and Serious Cardiovascular Events
Key Takeaways:
- Tirzepatide cut the combined risk of heart attack, stroke and death by around a third compared with sitagliptin over one year.
- Hospital admissions for infection fell by 36 per cent, and infection-related deaths by 60 per cent.
- Real-world insurance data offers evidence on GLP-1 medications that clinical trials have not yet produced.
A large real-world comparison of two diabetes medicines
People living with type 2 diabetes and obesity may gain substantially more than improved blood glucose control from treatment with tirzepatide. New research indicates that the medication, marketed as Mounjaro, is associated with roughly a one-third reduction in the risk of heart attack and a similar reduction in hospital admissions for infection, when compared with a conventional diabetes medication.
The findings come from researchers at the Technical University of Munich (TUM) and Harvard Medical School, who used health insurance data to examine how the drug performs outside the tightly controlled conditions of a clinical trial. Their study has been published in The BMJ.
What the researchers did
The team analysed a large dataset drawn from United States health insurance providers, comparing outcomes among people treated with tirzepatide against those treated with sitagliptin. Sitagliptin was chosen deliberately: it is a diabetes medication regarded as neutral with respect to cardiovascular outcomes, which makes it a useful yardstick for isolating any additional benefit attributable to tirzepatide.
That design matters. Rather than measuring tirzepatide against a placebo, the researchers set it against an established, widely used treatment that people with type 2 diabetes might realistically be prescribed instead – a comparison closer to the decisions clinicians and patients actually face.
Cardiovascular events reduced by around a third
The results pointed to clear advantages for the GLP-1 medication, a class that has drawn considerable public attention in recent years for its effects on weight.
After one year, 4.4 per cent of people treated with the comparator drug had experienced a heart attack or a stroke, or had died. Among those treated with tirzepatide, the figure was 2.9 per cent. The gap corresponds to a relative risk reduction of approximately one third.
Expressed in absolute terms, the difference of roughly 1.5 percentage points over a single year is meaningful in a population already carrying elevated cardiovascular risk from both type 2 diabetes and obesity.
Fewer hospital admissions for infection
The second set of findings was less anticipated. Significantly fewer people treated with tirzepatide were admitted to hospital with infections, with the associated risk reduced by 36 per cent. The risk of dying from an infection was reduced by as much as 60 per cent.
“The data on infections surprised us because the findings were so striking,” says Dr. Nils Krüger, first author of the study and a resident physician in the Department of Cardiovascular Diseases at TUM University Hospital. “Previous studies have suggested that people treated with GLP-1 agonists are less likely to be hospitalized for infections and less likely to die from them.”
In other words, the direction of the signal was not new – but its size was.
Why obesity may affect the immune response
According to Dr Krüger, the reasons behind the association are not yet fully understood. One plausible explanation lies in the relationship between excess adiposity and chronic inflammation.
“There is evidence that obesity promotes inflammatory processes in the body, which may in turn impair immune function. The exact mechanisms and whether this apparent benefit would also occur without weight loss now need to be investigated.”
That final point is the crux of the open question. If the protective effect is driven principally by weight loss, it would be expected to accompany any effective weight management intervention. If it persists independently of weight change, it would suggest something about the medication’s action on inflammatory or immune pathways that has yet to be characterised. Distinguishing between those possibilities will require dedicated research.
Building healthcare professionals’ understanding of how medications in this class work – and how to interpret emerging evidence about their wider effects – is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course.
How routine clinical data complements traditional trials
In Dr Krüger’s view, studies that draw on routine clinical data to compare the effects of medications are an important complement to conventional clinical trials. This is particularly true for GLP-1 agonists such as tirzepatide and semaglutide, sold as Mounjaro, Wegovy and Ozempic.
Because these medications have been on the market for a relatively short time, only a small number of large-scale studies have examined the full range of effects associated with the class. Medical societies and regulatory authorities need more research of this kind to underpin their recommendations.
There is also a practical problem that database research helps to solve. “Clinical trials are increasingly comparing active ingredients with one another,” says Dr Krüger. Regulatory authorities, however, often also require comparisons against the established standard of care rather than against another modern drug – a requirement that raises an ethical difficulty if it means assigning trial participants to older treatment while withholding a therapy that may benefit them.
“Database studies that are benchmarked against the results of traditional clinical trials can fill this gap without actually withholding potentially beneficial therapies such as GLP-1 agonists from study participants,” he says.
What this means for clinical decision-making
By enabling a direct comparison with standard diabetes treatment, Dr Krüger hopes the study will provide an additional tool to support decision-making by patients and their physicians.
For healthcare professionals supporting people who live with both type 2 diabetes and obesity, the practical implication is that the conversation about tirzepatide may extend well beyond glycaemic control and weight. Cardiovascular protection and, potentially, resilience to serious infection now form part of the evidence that can be weighed when treatment options are discussed.
As with all analyses of routinely collected data, the findings describe an association rather than establishing cause and effect, and the mechanisms behind the infection results remain to be confirmed. What the study adds is real-world evidence at a scale, and against a comparator, that trials have not yet delivered.
CCH insight
It seems that every week we learn of a new benefit attributable to GLP-1 based medications – this time a significant reduction in infections in patients taking tirzepatide. In view of the links between central adiposity and vitamin D deficiency, and the fact that vitamin D plays an important role immunity, it would be interesting to know if these results might be linked to improved vitamin D status as a result of abdominal fat loss.
Findings like these show how quickly the evidence base around GLP-1 medications is expanding, and how much rests on the professionals discussing these treatments understanding both how they work and how to appraise new data with confidence. CCH’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work CPD short course (2 CPD hours, fully online, CPD-accredited) gives healthcare professionals, whether or not they prescribe, a clear grounding in the science behind medications such as tirzepatide, where they fit in treatment pathways, and how to weigh emerging evidence critically.
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Weight Bias at Work: What New GLP-1 Research Reveals About Women’s Employment Prospects
Key Takeaways:
- Women who were unemployed when they started GLP-1 medications saw their employment rate rise by nearly 27 percentage points over 18 months, according to a 2026 NBER working paper.
- The gains appeared only among women entering the workforce – those already employed saw no rise in pay or promotion, pointing to perception rather than capability.
- The findings echo long-standing evidence on the financial cost of weight bias, from documented pay gaps to hiring professionals’ judgements based on photographs alone.
A new way to measure an old problem
For years, economists have documented what they call the “obesity penalty” – the social and financial disadvantages people can face because of their weight. It has been a difficult phenomenon to measure cleanly, because the factors that shape someone’s body weight also tend to shape their income, health and opportunities.
The rapid uptake of GLP-1 medications has given researchers something closer to a natural experiment. When large numbers of people begin treatment within a short window, and others who want the same treatment have not yet been able to start, it becomes possible to compare two otherwise similar groups and observe what changes.
That is the approach taken in a 2026 working paper published by the National Bureau of Economic Research, in which Harvard economist Rebecca Diamond examined what happened to women’s employment after they began taking GLP-1 medications.
What the researchers did
Diamond looked at survey data from around 15,000 people. She compared women who had started taking GLP-1 medications with similar women who wanted to take them but had not yet started. The two groups were matched on factors including income, race, body mass index and overall health, so that the comparison was not simply between people in very different circumstances to begin with.
The design matters. Because the comparison group consisted of women who also wanted the medications, the study is less vulnerable to the criticism that people who seek treatment are systematically different in motivation from those who do not.
The result that stands out
Among women who were unemployed at the point they began treatment, the employment rate rose by nearly 27 percentage points over the following 18 months, compared with the matched group who had not yet started.
To put that figure in context, it is a larger gap than the difference in employment between American women with a high school diploma and those holding a university degree. In other words, an 18-month change in body weight was associated with a bigger shift in employment than several years of formal education.
The research does not suggest that losing weight made these women more intelligent, more capable or better qualified for work. Nothing about their skills, experience or credentials changed. What the study raises is a different and more uncomfortable question: whether a change in appearance alters how women are perceived by employers.
Changes beyond the workplace
The effects were not confined to employment. The study also found that single women taking GLP-1 medications were nearly 29 percentage points more likely to get married or move in with a partner than similar women who had not started treatment.
Taken together, the employment and partnership findings describe something broader than a labour market effect. They describe a shift in social response.
The financial cost of weight bias
GLP-1 medications have moved quickly into the mainstream. In 2026, 11% of US adults said they were currently taking one to lose weight, up from just 3% in 2024, according to Gallup.
But the question of how weight shapes women’s working lives long predates the current wave of prescribing. Research was already pointing in this direction well before GLP-1 medications entered the cultural conversation.
What hiring professionals saw
A report from Fairygodboss, an employer review site for women, offered a particularly troubling look at how appearance can shape hiring decisions. In one study, hiring professionals were shown images of women with different body types and asked to evaluate them.
The woman pictured at the highest body weight was judged far more harshly than the others. Twenty percent of respondents described her as “lazy”, a label applied less frequently to every other woman pictured. Just 18% said she appeared to have leadership potential, while 21% described her as “unprofessional”.
These are judgements made on the basis of a photograph alone, with no information about experience, qualifications or performance.
Earnings gaps documented long before GLP-1 medications arrived
The pay data tells a similar story. In 2011, the Federal Reserve Bank of St Louis cited research finding that white women living with overweight earned about 4.5% less than white women whose BMI fell within what researchers classified as the normal range. White women living with obesity earned nearly 12% less.
Two caveats are important here. Those figures were specific to white women and do not apply to everyone. They also say nothing about anyone’s value, ability or contribution. What they suggest is that weight-related bias was already showing up in some women’s pay long before GLP-1 medications became widely available.
When appearance pays
The argument that appearance carries an economic premium is not new, and it is sometimes made bluntly. Codie Sanchez, CEO and founder of Contrarian Thinking, has said that women who wear makeup to work earn about 30% more on average than women who do not.
“Pretty privilege is very real,” she said on an episode of The Burnouts Podcast. “And you can either say ‘That’s not fair, so I’m not doing it.’ or you can win.”
Sanchez acknowledged that the advantage is unfair, but argued that women should use it rather than ignore it. “If it’s going to make me more money to paint my face, clown me up,” she said.
Diamond’s findings suggest weight bias may operate along similar lines. The women who benefited most were those seeking to enter the workforce, where first impressions carry disproportionate weight and where an employer’s judgement is formed quickly and on limited information. For women already in a job, whose managers had direct evidence of their performance, the effect disappeared.
Why this matters in clinical practice
For healthcare professionals, findings like these complicate the consultation room. People starting GLP-1 medications may be motivated by clinical goals, social goals, economic goals, or some mixture of all three, and those motivations shape expectations, adherence and how someone responds if treatment is paused or stopped.
Understanding the pharmacology well enough to have that conversation credibly is increasingly part of everyday practice rather than a specialist concern. Building that grounding is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work, a CPD-accredited online short course covering GLP-1 physiology and pharmacology for prescribers and non-prescribers alike.
An uncomfortable conclusion
Losing weight does not make a person more intelligent, more capable, harder working or better qualified for a job. But it may change how other people perceive them.
That is precisely what makes Diamond’s findings difficult to sit with. If some women gain access to more opportunities after losing weight while their underlying abilities remain exactly the same, then the economic benefit is not really a benefit at all. It is a measure of how heavily appearance still shapes the way women are perceived and treated – and of how much value has been withheld from them beforehand.
The medication changed the response. It did not change the woman.
CCH insight
Findings like these are a reminder that GLP-1 medications carry social and economic weight as well as clinical effect – and that patients arrive at the consultation with motivations shaped by far more than a treatment target. CCH’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work CPD short course (2 CPD hours, fully online, CPD-accredited) builds the foundation in GLP-1 physiology and pharmacology that healthcare professionals need to explain the science clearly, set realistic expectations and contribute confidently to treatment discussions, whether or not they prescribe.
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Sensing, Liking and Wanting: Why Food Feels Different on GLP-1RAs
Key Takeaways:
- A Frontiers in Nutrition review finds that altered eating experience on GLP-1 receptor agonists (GLP-1RAs) reflects changes in food reward rather than impaired taste function.
- The authors separate three processes: sensing food, liking it, and wanting it.
- The evidence is heterogeneous and largely observational, so the framework is a conceptual model, not proof of causality.
Why reports of “taste changes” may not be about taste at all
Some people taking GLP-1RAs report that their favourite foods become less enjoyable or tempting, without this necessarily reflecting impaired basic taste function. That distinction sits at the centre of a recent review published in the journal Frontiers in Nutrition, in which the authors conducted a structured narrative review of current evidence on how glucagon-like peptide-1 receptor agonists influence sensory perception, food enjoyment and food motivation, using a sensory-liking-wanting framework.
Obesity is a chronic, progressive metabolic disease with growing global prevalence, which increases the demand for effective long-term treatment options. GLP-1RAs are widely used in obesity treatment because they enhance satiety, delay gastric emptying, reduce energy intake and support meaningful weight loss. Alongside those effects, some people also report that food tastes different, feels less enjoyable, or no longer seems tempting. These experiences are often described as “taste changes”, but the review argues that they may reflect several biological processes rather than a single taste disorder. Further research is needed to understand these mechanisms and to improve nutritional care during treatment.
Looking beyond appetite suppression
GLP-1RAs have changed the way obesity is managed by reducing energy intake and supporting meaningful weight loss. Growing clinical experience, however, shows that their effects extend beyond a simple reduction in hunger.
Some people describe food tasting different, reduced pleasure in eating, or lower cravings for high-calorie foods. The review suggests that these experiences should not be treated as simple taste disturbances, but as a combination of three components related to eating behaviour: sensory perception, liking and wanting.
The three components of eating behaviour
Eating begins with sensory perception, which includes detecting taste, smell and food texture. This stage determines how food is initially recognised.
The second component is liking, defined as the subjective pleasure or hedonic value associated with eating. It is influenced by flavour, prior experience, context, cognitive factors and physiological state.
The third component, wanting, describes the motivation or craving to seek out and consume food. Separating these components helps explain why reports of “taste changes” may in fact reflect different biological processes.
How GLP-1RAs may influence food reward and the eating experience
The review sets out how GLP-1RAs may influence eating behaviour through interconnected biological pathways rather than by directly changing taste. Preclinical studies indicate that endogenous glucagon-like peptide-1 (GLP-1) is produced by some mammalian taste bud cells and may modulate taste signalling. Those findings do not establish that GLP-1RA treatment directly alters taste in humans, and the limited human studies available have produced inconsistent results.
Taste signals are integrated in the nucleus of the solitary tract (NTS) before reaching brain regions involved in appetite and reward. Human studies have associated GLP-1RA treatment with reduced craving and weaker neural responses to calorie-dense food cues in some participants. Those findings are more consistent with altered food valuation and motivation than with impaired basic taste.
Gastrointestinal effects, including nausea and early satiety, may also reduce the pleasure of eating, which makes it difficult to distinguish altered food reward from genuine changes in taste perception.
What the clinical evidence does and does not show
Randomised controlled trials usually focus on body weight and metabolic outcomes. Eating-related experiences are rarely included as prespecified measures and are more often captured sporadically as adverse events.
Patient-reported outcome questionnaires may provide a more sensitive window into changes in food enjoyment and preference, but assessment methods vary considerably between studies. Real-world evidence presents additional challenges, as reports of “taste alterations” may encompass several distinct sensations, including olfactory changes, dry mouth, gastrointestinal discomfort and other symptoms that are difficult to distinguish clinically.
Spontaneous reporting databases can identify safety signals but cannot establish incidence or risk. Cohort studies, by contrast, provide better-defined populations and follow-up, yet remain vulnerable to subjective reporting and confounding.
Because this was a narrative review rather than a systematic review or meta-analysis, the authors did not conduct a formal risk-of-bias assessment.
A framework for understanding what people report
According to the review, alterations in the eating experience during GLP-1RA treatment should not be regarded solely as a biological phenomenon, but understood as the interaction between different processes.
Peripheral taste pathways, brainstem integration, central reward networks, interoceptive state and learned behaviour may all contribute. Their relative importance may differ between individuals and across treatment stages. A person’s report of a “taste change” may therefore not correspond to a clinically defined gustatory disorder.
The authors also note that alternative explanations should be considered when interpreting eating-related changes, including nausea, delayed gastric emptying, altered satiety, behavioural adaptation and medication adherence.
The framework additionally accommodates limited treatment response, persistent appetite, weight regain after treatment withdrawal or interruption, and rare atypical or paradoxical responses.
Clinical relevance and a possible stage-dependent pattern
The review highlights that reported changes in eating experience should not automatically be classified as taste abnormalities. Healthcare professionals may find it useful to establish whether a person is describing altered taste perception, reduced satisfaction from eating, or diminished interest in food, as these experiences can reflect distinct processes. Distinguishing between them well depends on the quality of the conversation in the consultation, and supporting people through the eating-related changes that accompany GLP-1RA treatment is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Practice: Supporting Patients During Treatment, a CPD-accredited online short course.
The authors present these points as translational implications rather than formal clinical recommendations. They also propose a stage-dependent pattern in which these experiences may change over time.
Early in treatment, gastrointestinal discomfort and enhanced satiety may reduce the appeal of food, whereas later stages may involve a more persistent reduction in motivation towards highly rewarding foods in some individuals.
Why this matters for nutrition and obesity management
The proposed sensory-liking-wanting framework has practical implications for obesity treatment and nutritional counselling. Understanding whether someone is experiencing altered sensory perception, reduced enjoyment of food, or lower motivation towards food may support more individualised dietary guidance and improve communication between people receiving treatment and the professionals caring for them.
The review also highlights that the existing body of evidence is heterogeneous, owing to differences in endpoint definitions, measurement methods, populations, drugs, doses and follow-up periods. Much of the human evidence is observational, secondary or exploratory, and many studies were not designed to separate sensory function from liking and wanting. Current findings are therefore better interpreted as a conceptual framework for organising available evidence than as proof of a single causal pathway.
Future studies using standardised, multimodal assessments and longer follow-up may help clarify how these eating-related changes influence food preferences, dietary behaviour, long-term weight management and treatment adherence.
Conclusion
The review concludes that altered eating experiences during GLP-1RA therapy are more consistent with changes in food reward, hedonic evaluation and motivational drive than with a uniform impairment of taste function, although modulation of peripheral taste pathways may contribute in some cases.
Current evidence supports interpreting reported “taste changes” within a sensory-liking-wanting framework that distinguishes sensory perception from food enjoyment and craving. Because responses vary between individuals and the available evidence remains heterogeneous, the proposed framework should be considered a conceptual model rather than definitive proof of causality.
Longitudinal, multimodal human studies measuring sensory function, hedonic response, motivational drive and state-related symptoms in parallel are needed to clarify these effects and their implications for nutrition, dietary behaviour, treatment adherence and long-term obesity management.
CCH insight:
When someone says food no longer tastes right on a GLP-1RA, the clinically useful question is which part of eating has changed: the sensing, the liking or the wanting. Each points towards different advice, and each can shift as treatment progresses. CCH’s GLP-1RAs in Practice: Supporting Patients During Treatment CPD short course (2 CPD hours, fully online, CPD-accredited) equips healthcare professionals to have exactly those conversations – recognising what people are really describing, adapting dietary and nutritional support through the course of treatment, and monitoring for the changes that matter.
Explore GLP-1RAs in Practice: Supporting Patients During Treatment →
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GLP-1 Therapies Linked to Lower Fragility Fracture Risk in Adults Living With Type 2 Diabetes
Key Takeaways:
- Adults aged 50 and over living with type 2 diabetes who started a GLP-1 receptor agonist had a 21% lower three-year risk of fragility fracture than those starting a DPP-4 inhibitor (HR 0.79).
- Reductions were strongest for vertebral (HR 0.68) and hip or femur fractures (HR 0.70), and appeared independent of changes in BMI and HbA1c – pointing to a possible direct skeletal effect.
- The findings do not extend to younger people using GLP-1 medications for weight management alone, or to those with osteoporosis; among adults without diabetes, fracture risk was higher (HR 1.13).
A large-scale look at bone health during GLP-1 treatment
Initiating a GLP-1 receptor agonist for type 2 diabetes was associated with a lower risk of fragility fractures in adults aged 50 and over, including fractures of the hip and spine, according to a large target trial emulation study published in JAMA Network Open.
Over three years of follow-up, adults who newly started a GLP-1 medication had a 21% lower risk of fragility fracture than those who newly started a DPP-4 inhibitor (HR 0.79, 95% CI 0.76–0.83), reported Christopher Hamad, MD, of the University of California Los Angeles, and colleagues.
The authors were careful to frame the size of the effect in context rather than overstate it.
“Although the absolute risk reduction at 3 years was modest (0.79%), this magnitude is clinically relevant given a baseline 3-year major osteoporotic fracture risk of approximately 3% to 4% in comparable populations and the substantial morbidity and mortality associated with hip and vertebral fractures,” the authors wrote.
Why a modest absolute reduction still matters
The clinical weight of these numbers rests on how serious the events being prevented are. Hip fractures, for example, are associated with one-year mortality rates of up to 25% in women and up to 36% in men.
Given the potential for such severe outcomes, Hamad’s group emphasised that even modest absolute reductions in fragility fractures – which stem from low-energy trauma, such as a fall from standing height – can prevent a meaningful number of events at population level.
The findings build on several smaller observational studies in people living with diabetes that have similarly linked the use of GLP-1 medications such as semaglutide (Ozempic, Wegovy) to a reduced fracture risk. Hamad’s team noted that their analysis drew on the largest dataset assembled on this question to date.
Which fractures showed the strongest signal
The protective association was most pronounced at precisely the sites that carry the highest morbidity and mortality:
- Vertebral fractures: HR 0.68, 95% CI 0.63–0.73
- Hip or femur fractures: HR 0.70, 95% CI 0.63–0.79
- Rib fractures: HR 0.83, 95% CI 0.77–0.91
No significant associations were identified for fractures of the distal radius or ulna, or of the proximal humerus.
Weight loss, glycaemic control and the question of a direct skeletal effect
One of the more striking elements of the analysis concerns the mechanism. Mediation analyses indicated that the associations were independent of changes in BMI and HbA1c, a pattern consistent with a potential direct skeletal effect of GLP-1 medications.
That matters because weight loss itself is associated with reduced bone mineral density and a higher fracture risk – a relationship reflected in the study’s own data, which found that cumulative BMI loss was tied to a 2% increase in fracture risk. In other words, the expected consequence of the weight reduction these medications produce would be a rise in fracture risk, not a fall.
“Yet, GLP-1 RA [receptor agonist] use was associated with lower fracture risk despite these changes, suggesting that potential direct skeletal effects may outweigh the adverse consequences of weight loss,” the authors wrote.
Reassessing the assumption of neutral skeletal effects
Current American Diabetes Association Standards of Care classify GLP-1 medications as having neutral effects on the skeleton. The researchers argued that their results suggest this assumption warrants reevaluation.
They also acknowledged the limits of what an observational design can establish, noting that the findings could still reflect unmeasured factors such as improved balance or greater physical activity among people taking these medications. Making sense of evidence like this – and of the mechanistic arguments used to interpret it – is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course that grounds healthcare professionals in how these medications act on the body.
How the study was conducted
For this comparative effectiveness study, the researchers drew data from the TriNetX Research Network, analysing 66,803 matched pairs, or 133,606 people in total, aged between 50 and 90 years.
Mean age was approximately 63 years, roughly 53% of participants were male, 58% were White, and average baseline BMI was around 33.
All participants were living with type 2 diabetes and had newly initiated either a GLP-1 receptor agonist or a DPP-4 inhibitor between 2015 and 2022. Dulaglutide (Trulicity), semaglutide and liraglutide (Victoza) together accounted for 91% of index prescriptions in the GLP-1 group. Exclusion criteria included fractures resulting from high-energy trauma, as well as osteoporosis and osteopenia.
Where the protective association held – and where it did not
In subgroup analyses, the lower fracture risk was consistent across age groups, across sexes and across levels of frailty.
A separate matched cohort, however, evaluated participants according to diabetes status and produced a notably different picture. Among adults living with type 2 diabetes, GLP-1 use retained a protective association (three-year HR 0.91, 95% CI 0.88–0.95). Among adults without diabetes, it was associated with an increased fracture risk (HR 1.13, 95% CI 1.04–1.23, P<0.001 for interaction).
Consequently, the authors emphasised that the findings cannot be generalised to younger people using GLP-1 medications solely for weight management, nor to those with known osteoporosis or a previous fragility fracture, who were excluded from the study altogether.
What this means for practice
Overall, “the findings do not argue against GLP-1 RA use on the basis of fracture risk, though bone health monitoring remains prudent,” according to the researchers.
They called for prospective randomised trials to evaluate the associations observed, including among people with osteopenia or early osteoporosis, alongside preclinical work to understand the potential mechanisms involved.
CCH insight
For healthcare professionals, this study is a useful reminder that the skeletal consequences of GLP-1 treatment are not yet settled science – and that the answer appears to differ depending on who is being treated and why. Interpreting findings of this kind with confidence depends on a firm grasp of how these medications act in the first place, from gut hormones and appetite regulation through to their wider effects beyond glycaemic control. That 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 provide, giving clinicians a clear grounding in the mechanisms behind these therapies and the ability to appraise emerging evidence critically, whether or not they prescribe.
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