BMJ medicine最新文献

{"title":"Correction: Metabolic dysfunction associated steatotic liver disease: mechanisms, diagnosis, and management in adults.","authors":"","doi":"10.1136/bmjmed-2025-002038corr1","DOIUrl":"10.1136/bmjmed-2025-002038corr1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1136/bmjmed-2025-002038.].</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e002038corr1"},"PeriodicalIF":9.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and emerging therapies for pulmonary tuberculosis in adults.","authors":"Amira Mahmood, Mohammad Bilal Ashfaq, Catherine Drain, Eoin Melby, Michael Hunter, Timothy David Shaw","doi":"10.1136/bmjmed-2025-001836","DOIUrl":"10.1136/bmjmed-2025-001836","url":null,"abstract":"<p><p>Tuberculosis remains the biggest global killer from infectious causes, with an estimated 1.25 million deaths per year. The quadruple drug regimen of rifampicin, isoniazid, pyrazinamide, and ethambutol has been standard therapy for 40 years, with good outcomes in patients with drug susceptible tuberculosis who are able to tolerate the drug regimen. However, the frequency of adverse drug reactions and emergence of drug resistant tuberculosis has created demand for new treatment strategies: there is now a surge in novel tuberculosis agents and regimens entering human trials. For decades, drug resistant tuberculosis required at least 18 months of second line and third line combination treatments that included injectable agents. In 2022, in response to a growing body of trial evidence, the World Health Organization (WHO) introduced six month and nine month all oral regimens for pulmonary drug resistant tuberculosis in specific settings. These encompass agents in the bedaquiline-pretomanid-linezolid/moxifloxacin regimen, as well as repurposed and novel agents such as clofazimine and delamanid. In addition, a large number of novel antimicrobial and host directed treatments are progressing to late stage clinical trials for tuberculosis, raising the prospect of shorter, more efficacious, and better tolerated treatments. This review summarises the agents and regimens recommended in the latest consolidated WHO treatment guidelines for tuberculosis (2025), including a synopsis of the evidence base for their safety, efficacy, and cost effectiveness. It also outlines the antimicrobial and host directed treatments that have entered phase 2-4 clinical trials for pulmonary tuberculosis in adults.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e001836"},"PeriodicalIF":9.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fragility fracture, atypical femoral fracture, and osteonecrosis of jaw after bisphosphonate prescription for three and five years, based on primary and secondary care data in England: nested case-control and cohort studies.","authors":"Georgina Nakafero, Tricia McKeever, Niraj S Kukreja, Victoria Welsh, Sara Muller, Abhishek Abhishek","doi":"10.1136/bmjmed-2025-002085","DOIUrl":"10.1136/bmjmed-2025-002085","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the association between fragility fracture and interruption of bisphosphonate prescription after three and five years of initial prescription, and to explore the incidence of atypical femoral fracture and osteonecrosis of jaw after three and five years of continued prescription of bisphosphonates.</p><p><strong>Design: </strong>Nested case-control and cohort studies.</p><p><strong>Setting: </strong>Clinical Practice Research Datalink Aurum, an anonymised longitudinal database of NHS primary care electronic health records, linked to hospital admission and mortality records from Hospital Episode Statistics and Office for National Statistics databases, respectively, 1 January 1997 to 31 December 2022.</p><p><strong>Participants: </strong>Adults aged ≥18 years on the date of the first prescription of alendronate or risedronate, and with primary care data linked to Hospital Episode Statistics and Office for National Statistics databases. Participants with a medication possession ratio of ≥67% in each of the first three and five years were followed up from the three or five year time points to the earliest of fragility fracture, death, end of study, two years, or last data availability. Cases were those who had a fragility fracture and were matched with up to four control participants.</p><p><strong>Main outcome measures: </strong>Incidence of fragility fracture, atypical femoral fracture, and osteonecrosis of jaw were main outcomes.</p><p><strong>Results: </strong>Data for 26 809 and 13 408 participants prescribed bisphosphonates for three and five years, respectively, were included. Fragility fracture was not associated with interruption of bisphosphonate prescription or intermittent prescription compared with continuous prescription in those previously prescribed bisphosphonates for three years (adjusted odds ratio 1.02, 95% confidence interval (CI) 0.85 to 1.24 and 1.13, 0.93 to 1.38, respectively) or five years (adjusted odds ratio 0.92, 0.75 to 1.13 and 0.87, 0.67 to 1.13, respectively). Time since last prescription was not associated with fragility fracture. After three and five years of bisphosphonate prescription, the incidence of atypical femoral fractures was 1.93 (95% CI 1.55 to 2.41) and 2.50 (1.92 to 3.26) per 1000 person years, respectively, and the incidence of osteonecrosis of jaw was 0.07 (0.02 to 0.21) and 0.00 per 1000 person years, respectively, within two years.</p><p><strong>Conclusion: </strong>Fragility fracture was not associated with interruption of bisphosphonate prescription for up to two years, after either three or five years of prescription. The incidence of atypical femoral fracture or osteonecrosis of jaw was uncommon and rare respectively.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e002085"},"PeriodicalIF":9.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists and risk of all cause and cause specific acute pancreatitis: target trial emulation.","authors":"Yan Xie, Taeyoung Choi, Ziyad Al-Aly","doi":"10.1136/bmjmed-2025-002183","DOIUrl":"10.1136/bmjmed-2025-002183","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To assess whether initiation of glucagon-like peptide-1 receptor agonists (GLP-1RAs) rather than sulfonylureas is associated with all cause acute pancreatitis and cause specific acute pancreatitis and to characterise temporal risk patterns of the various causes of acute pancreatitis associated with GLP-1RA use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Target trial using the electronic healthcare databases of the US Department of Veterans Affairs healthcare system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;US Department of Veterans Affairs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;333 687 users of the Veterans Affairs healthcare system with type 2 diabetes initiating GLP-1RA (n=132 551) or sulfonylureas (n=201 136) between 1 January 2017 and 31 December 2023.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposure: &lt;/strong&gt;Initiation of GLP-1RA or sulfonylureas, and separately, continued use of GLP-1RA or sulfonylureas during follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;Risks of acute pancreatitis during 12 months' follow-up including all cause acute pancreatitis and cause specific acute pancreatitis (eg, pancreatitis that is suspected drug induced, alcohol induced, hypertriglyceridaemia associated, biliary, and idiopathic or other cause). The risks were measured through discrete time survival models after application of inverse probability weighting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In intention-to-treat analyses, participants who initiated GLP-1RAs had similar rates of all cause pancreatitis at one year compared with participants who initiated sulfonylureas (rate difference -3.64, 95% confidence interval (CI) -30.76 to 23.48 per 100 000 persons at one year). However, the overall null finding was the net result of countervailing effects across various causes of acute pancreatitis. GLP-1RA was associated with an increased risk of suspected drug induced acute pancreatitis (23.45 (14.27 to 33.85)) and decreased risks of hypertriglyceridaemia associated (-16.96 (-27.41 to -7.34)) and alcohol induced pancreatitis (-10.32 (-18.12 to -3.17)). Similar rates of biliary and idiopathic or other causes of acute pancreatitis were observed in the two groups. In per protocol analyses, drug induced acute pancreatitis attributable to GLP-1RA clustered early (42% of GLP-1RA attributable events over one year of follow-up occurred in the first three months), whereas reductions in alcohol related acute pancreatitis concentrated between months four and six and hypertriglyceridaemia associated acute pancreatitis concentrated between months 10 and 12. Cumulatively, these divergent temporal trends resulted in a net increase in risk of all cause pancreatitis during the first two months of treatment, with similar monthly risk observed for the remainder of follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this nationwide cohort, similar rates of all cause acute pancreatitis in GLP-1RA and sulfonylurea users were observed at one year. Increased risk of suspected drug induced pancreatitis","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e002183"},"PeriodicalIF":9.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary care and community interventions for multimorbidity involving depression or anxiety: systematic review with meta-analysis.","authors":"Kieran Sweeney, Michaela Gilarova, Lauren Ng, Jennifer Baker, Susanne Maxwell, Clare Macrae, Stewart W Mercer, Atul Anand, Bruce Guthrie, Lucy E Stirland","doi":"10.1136/bmjmed-2025-002400","DOIUrl":"10.1136/bmjmed-2025-002400","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To identify and characterise primary care or community based interventions for patients with multimorbidity involving depression or anxiety, and to determine their effectiveness for improving patients' mental health, physical health, and quality of life.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Systematic review with meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data sources: &lt;/strong&gt;Medline, Embase, Cochrane Library, CINAHL, PsycInfo, and Web of Science databases, from inception to 11 November 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Eligibility criteria for selecting studies: &lt;/strong&gt;Included studies were randomised controlled trials of primary care or community based interventions targeting adults with depression or anxiety disorders and one or more long term physical conditions. Risk of bias assessment used the Cochrane risk of bias tool. Interventions were categorised as organisational or patient oriented, and were subgrouped by intervention type. Intervention components were systematically categorised, and effects on mental health and quality of life outcomes were meta-analysed in groups defined by intervention type and assessment time point. Physical health outcomes were too heterogenous to meta-analyse and were synthesised without meta-analysis with Fisher's method for combining P values.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;29 randomised controlled trials comprising 9487 participants were included. High quality evidence was found for organisational interventions (n=10, including collaborative care, stepped care, and post-discharge interventions) which resulted in small improvements in symptoms of depression (standardised mean difference -0.25, 95% confidence interval (CI) -0.43 to -0.06) and quality of life (0.21, 0.01 to 0.41), but had no effect on symptoms of anxiety at the end of the intervention. No effect on depression or anxiety symptoms was observed, and no data for quality of life were found from organisational interventions at the late follow-up period (18-24 months). In the subgroup analysis, collaborative care resulted in sustained improvements in symptoms of depression at 18-24 months. Synthesis without meta-analysis showed evidence of benefit from organisational interventions (specifically collaborative care) on physiological (eg, haemoglobin A&lt;sub&gt;1c&lt;/sub&gt; levels), but not on functional (eg, disability) or global physical health outcomes. Low to moderate quality evidence was found for patient oriented interventions (n=19; interventions including exercise, psychotherapy, and psychoeducation) which led to small improvements in symptoms of depression (standardised mean difference -0.46, 95% CI -0.71 to -0.21) and quality of life (0.22, 0.14 to 0.29) at the end of the intervention. These effects were diminished at the late follow-up period (≥12 months). In the subgroup analysis, no reported data for the long term effects of exercise, psychotherapy, or psychoeducation (18-24 months after randomisation) were found. Synthesis without meta-analysis sh","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e002400"},"PeriodicalIF":9.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Physical activity types, variety, and mortality: results from two prospective cohort studies.","authors":"","doi":"10.1136/bmjmed-2025-001513corr1","DOIUrl":"10.1136/bmjmed-2025-001513corr1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1136/bmjmed-2025-001513.].</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e001513corr1"},"PeriodicalIF":9.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine cold chain and understanding what underpins vaccine security for vaccine preventable diseases.","authors":"Gilbert Rukundo, Matthew Moore, Herve Semukunzi, Sudeshna Chatterjee, Jean Pierre Musabyimana, Claude Mambo Muvunyi, Christopher Aird Green","doi":"10.1136/bmjmed-2025-001835","DOIUrl":"10.1136/bmjmed-2025-001835","url":null,"abstract":"<p><p>Vaccines have saved an estimated 154 million lives in the past 50 years and support 15 of the 17 United Nations sustainable development goals. Vaccines are also an important tool in the control of new outbreaks of infectious diseases. The vaccine cold chain, however, is key in enabling and empowering implementation of vaccine policy and societal protection from all vaccine preventable diseases, and is especially relevant in low and middle income countries in sub-Saharan Africa. The vaccine cold chain is a complex, highly specialised, temperature controlled supply chain network that extends from the point of vaccine manufacture to dose administration, and has multiple points of vulnerability. Large quantities of vaccines are lost because of excess heat or accidental freezing, resulting in missed opportunities for vaccination. Disruption to the provision of routine vaccines during the covid-19 pandemic resulted in millions of children not being vaccinated. The vaccine cold chain needs strategic prioritisation for investment and innovation so that the next generation of vaccine cold chains for low and middle income countries can be designed towards providing reliable and sustainable vaccine security in an uncertain world of climate change, managing the advent of new vaccine technologies, and narrowing inequalities in global health for resource poor communities. This review focuses on the vaccine cold chain in African low and middle income countries, and how new and emerging advances in vaccine science and challenges will affect the readiness to control the burden of vaccine preventable disease on the continent.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e001835"},"PeriodicalIF":9.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dysfunction associated steatotic liver disease: mechanisms, diagnosis, and management in adults.","authors":"Tina Reinson, Josh Bilson, Caroline Childs, Ryan M Buchanan, Giovanni Targher, Christopher D Byrne","doi":"10.1136/bmjmed-2025-002038","DOIUrl":"10.1136/bmjmed-2025-002038","url":null,"abstract":"<p><p>Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally and a major cause of liver related and cardiometabolic morbidity. MASLD is defined by the presence of hepatic steatosis and at least one of five cardiometabolic features in the absence of secondary causes of liver disease and substantial alcohol consumption (>20 g/day for women and 30 g/day for men). The recent reclassification of non-alcoholic fatty liver disease to MASLD represents a paradigm shift towards recognising the central role of systemic metabolic dysfunction and cardiometabolic risk factors in the pathogenesis of the disease and development of complications. The pathophysiology of MASLD is complex, multifaceted, and interconnected, involving adipose tissue dysfunction, altered hepatic lipid metabolism, mitochondrial and endoplasmic reticulum stress, dysregulation of the gut-liver axis, and genetic predisposition. The severity of liver fibrosis remains the strongest predictor of all cause mortality and liver specific morbidity and mortality, and the burden of cardiometabolic dysfunction affects the risk of complications in MASLD. Non-invasive serum based and imaging based biomarkers are crucial in identifying advanced liver fibrosis and guiding risk stratification. This narrative review summarises the current understanding of the pathogenesis of MASLD, the clinical use of non-invasive diagnostics, and compares international guidelines for disease management. This review also discusses approved and emerging treatment options for MASLD, recognising the current need for developing strategies for monitoring the efficacy of treatment.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e002038"},"PeriodicalIF":9.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling lowering of raised blood pressure in pregnancy to reduce pre-eclampsia: secondary analysis of data from prospective cohort studies.","authors":"Alan Wright, Argyro Syngelaki, David Wright, Peter von Dadelszen, Kypros H Nicolaides, Laura A Magee","doi":"10.1136/bmjmed-2025-001631","DOIUrl":"10.1136/bmjmed-2025-001631","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether antihypertensive treatment of blood pressure levels of <140/90 mm Hg can reduce the incidence of pre-eclampsia.</p><p><strong>Design: </strong>Secondary analysis of data from prospective cohort studies.</p><p><strong>Setting: </strong>Three prospective screening studies of women who attended routine hospital maternity visits at 11-13 weeks' gestation, 1 February 2010 to 31 December 2016. Participants were from seven secondary care institutions in England.</p><p><strong>Participants: </strong>54 422 pregnancies screened at 11-13 weeks' gestation for pre-eclampsia and with blood pressure values available, that resulted in a liveborn or stillborn infant at ≥24 weeks' gestation.</p><p><strong>Main outcome measures: </strong>Incidence of pre-eclampsia (overall, and at preterm or term gestational ages), according to modelled blood pressure lowering.</p><p><strong>Results: </strong>The study population was ethnically diverse (17.3% black participants, 7.8% from South or East Asia, and 2.6% self-identified with more than one ethnic group). The Fetal Medicine Foundation competing risks model was used to calculate the expected risk of pre-eclampsia, based on maternal characteristics, mean arterial pressure, uterine artery pulsatility index, and placental growth factor. The expected risk of pre-eclampsia was used to calculate the expected incidence of pre-eclampsia. Reducing diastolic blood pressure from >85 mm Hg to a target of 85 mm Hg would mean that 4.8% of women would be offered antihypertensive drugs, with a potential relative risk reduction of 21.4% (absolute reduction of 2.9%) in any pre-eclampsia and 28.3% (absolute reduction of 1.4%) reduction in preterm pre-eclampsia. By reducing diastolic blood pressure from >80 mm Hg to a target of 80 mm Hg, 13.2% of women would receive antihypertensive drugs, with a potential relative risk reduction of 26.0% (absolute reduction of 2.3%) in any pre-eclampsia and 33.8% (absolute reduction of 1.0%) reduction in preterm pre-eclampsia. By reducing diastolic blood pressure from >75 mm Hg to a target of 75 mm Hg, 29.5% of women would receive antihypertensive drugs, with a potential relative risk reduction of 32.8% (absolute reduction of 2.1%) in any pre-eclampsia and 41.6% (absolute reduction of 0.8%) in preterm pre-eclampsia.</p><p><strong>Conclusions: </strong>Lowering blood pressure from early pregnancy may reduce preterm and term pre-eclampsia. This finding requires evaluation in a definitive randomised trial.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e001631"},"PeriodicalIF":9.3,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like peptide 1 receptor agonist discontinuation and risks of major adverse cardiovascular events in adults with type 2 diabetes: target trial emulation.","authors":"Yan Xie, Taeyoung Choi, Ziyad Al-Aly","doi":"10.1136/bmjmed-2025-002150","DOIUrl":"10.1136/bmjmed-2025-002150","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To characterise patterns of use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) and assess the associations between various GLP-1RA treatment scenarios and the risk of major adverse cardiovascular events.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Target trial emulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Electronic healthcare databases of US Department of Veterans Affairs, 1 January 2017 to 31 December 2023. Data obtained from domains in the Veterans Affairs Corporate Data Warehouse.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Veterans Affairs users with type 2 diabetes who started treatment with GLP-1RAs (n=132 551) or sulfonylureas (n=201 136), followed up for three years. Veterans Affairs users were defined as having at least two visits to Veterans Affairs and having used the Veterans Affairs outpatient pharmacy within a year before receiving treatment with GLP-1RAs or sulfonylureas.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;GLP-1RAs or sulfonylureas. In the GLP-1RA arm, treatment status was reassigned every six months, generating 16 prespecified treatment strategies that varied in length of continued use, discontinuation, or interruption.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;Three year cumulative incidence of major adverse cardiovascular events (myocardial infarction, stroke, or all cause death).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The cohort included 132 551 incident users of GLP-1RAs and 201 136 incident users of sulfonylureas (defined as no prescription for GLP-1RAs or sulfonylureas within a year of the first prescription). A duration dependent association was found between the use of GLP-1RAs and the cumulative three year risk of major adverse cardiovascular events. Compared with the sulfonylurea reference group, participants who used GLP-1RAs for 0.5, 1, or 1.5 years, before discontinuing for the remainder of the three years, showed incidence risk ratios close to 1.0, with no significant reduction in the risk of major adverse cardiovascular events at three years. Compared with the sulfonylurea group, the reduction in the risk of major adverse cardiovascular events was significant in people who continued to use GLP-1RAs for 2 and 2.5 years, before discontinuing for the remainder of the three years (incidence risk ratio 0.93, 95% confidence interval (CI) 0.88 to 0.98 and 0.85, 0.81 to 0.90, respectively). Participants who continued to use GLP-1RAs for the whole three year follow-up period had the most pronounced risk reduction (incidence risk ratio 0.82, 95% CI 0.78 to 0.85) compared with the sulfonylurea group. Compared with continued use of GLP-1RA, discontinuing treatment for 0.5 years was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio 1.04, 95% CI 1.01 to 1.08); the risk increased progressively with a longer duration of discontinuation, with an incidence risk ratio of 1.14 (1.09 to 1.18) and 1.22 (1.16 to 1.27) for one and two years of discontinuation, respectively. Co","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"5 1","pages":"e002150"},"PeriodicalIF":9.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}