Diabetologia最新文献

{"title":"Effect of acute exercise and exercise training on the ability of insulin to clear branched-chain amino acids from plasma in obesity and type 2 diabetes.","authors":"Pauline M Møller,Rasmus Kjøbsted,Maria H Petersen,Martin E de Almeida,Andreas J T Pedersen,Jørgen F P Wojtaszewski,Kurt Højlund","doi":"10.1007/s00125-025-06454-y","DOIUrl":"https://doi.org/10.1007/s00125-025-06454-y","url":null,"abstract":"AIMS/HYPOTHESISInsulin resistance in obesity and type 2 diabetes is associated with elevated plasma branched-chain amino acid (BCAA) levels. Here, we examined whether the ability of insulin to clear plasma BCAAs and any influence of acute exercise or exercise training on this response are intact in obesity and type 2 diabetes.METHODSIn four case-control studies of participants with type 2 diabetes matched to glucose-tolerant individuals with obesity and lean individuals, who underwent hyperinsulinaemic-euglycaemic clamps, we examined the effect of insulin on plasma BCAAs (studies I-IV), with or without prior acute exercise (60 min, 70% V ˙ O 2max ) (study II), and before and after 10 weeks of endurance exercise training (study III) or 8 weeks of high-intensity interval training (study IV).RESULTSInsulin sensitivity was reduced in individuals with type 2 diabetes compared with individuals with obesity (study I-IV) and lean individuals (studies I and IV), and in individuals with obesity vs lean individuals (study I) (all p<0.05). Exercise training (studies III and IV) increased insulin sensitivity in all groups (all p<0.01). Plasma BCAAs were elevated in individuals with type 2 diabetes compared with individuals with obesity (studies I, III and IV) and lean individuals (studies I and IV) (all p<0.05). The ability of insulin to reduce plasma BCAAs was significantly attenuated in participants with type 2 diabetes compared with both lean individuals (studies I and IV) and individuals with obesity (studies I, II and IV) (all p<0.05). Acute exercise slightly reduced plasma BCAAs in both individuals with type 2 diabetes and individuals with obesity but did not potentiate insulin's ability to reduce plasma BCAAs (study II). Exercise training had no impact on fasting BCAAs and did not affect insulin's ability to reduce plasma BCAAs in any group (studies III and IV) or rescue the attenuated insulin suppression of plasma BCAAs in participants with type 2 diabetes.CONCLUSIONS/INTERPRETATIONOur results demonstrate that insulin's ability to suppress plasma BCAAs is impaired in type 2 diabetes but is intact in individuals with obesity. Although acute exercise reduces fasting BCAA levels, neither acute exercise nor exercise training affects insulin's ability to suppress plasma BCAAs in glucose-tolerant individuals with or without obesity or in individuals with type 2 diabetes.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"137 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register - an IMI-SOPHIA study.","authors":"Martin Heni,Lisa Frühwald,Wolfram Karges,Michael Naudorf,Kathrin Niemöller,Frank Pagnia,Jörg Reindel,Jochen Seufert,Gisa Ufer,Christian Wagner,Reinhard W Holl,Nicole Prinz","doi":"10.1007/s00125-025-06448-w","DOIUrl":"https://doi.org/10.1007/s00125-025-06448-w","url":null,"abstract":"AIMS/HYPOTHESISGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice.METHODSData from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA1c and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA1c reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project.RESULTSAt 6 months' follow-up the median absolute HbA1c reduction was 5.3 mmol/mol (IQR 13.9, -1.0) (0.49% [1.27, -0.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA1c (absolute reduction ≥5.5 mmol/mol [0.5%]) and body weight (relative reduction ≥5%). Men and those with a higher baseline HbA1c were more likely to show an HbA1c only response (36% of participants; both p<0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both p<0.001). Higher baseline body weight and lower eGFR (both p<0.05) correlated with greater weight reduction, whereas lower baseline HbA1c and longer diabetes duration were linked to smaller HbA1c reductions (both p<0.001).CONCLUSIONS/INTERPRETATIONThere is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA1c. Future studies should explore why some individuals achieve either weight loss or HbA1c reduction but not both.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"18 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle mitochondrial health in type 1 diabetes: the role of exercise capacity and lifestyle factors","authors":"Richie P. Goulding, Braeden T. Charlton, Ellen A. Breedveld, Jelle Y. Huijts, Matthijs van der Laan, Anne R. Strating, Wendy Noort, Aryna Kolodyazhna, Anita E. Grootemaat, Frank W. Bloemers, Nicole N. van der Wel, Rob C. I. Wüst","doi":"10.1007/s00125-025-06451-1","DOIUrl":"https://doi.org/10.1007/s00125-025-06451-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Previous studies reporting lower skeletal muscle mitochondrial function in type 1 diabetes did not account for cardiorespiratory fitness, a key confounder when assessing mitochondrial function. We hypothesised that, compared with healthy individuals, muscle mitochondrial phenotypic differences would be abolished in individuals with type 1 diabetes when matched for age, sex, BMI and maximal oxygen uptake (<span>(dot{V}{text{O}}_{text{2max}})</span>).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and <span>(dot{V}{text{O}}_{text{2max}})</span> participated and underwent a muscle biopsy from the vastus lateralis. Mitochondrial respiration was assessed by high-resolution respirometry, and mitochondrial density and morphology were assessed by transmission electron microscopy.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p><span>(dot{V}{text{O}}_{text{2max}})</span> (individuals with type 1 diabetes 40±10 kg⁻¹ min⁻¹; control individuals 41±8 ml kg⁻¹ min⁻¹; <i>p</i>=0.51) and mitochondrial oxidative phosphorylation capacity (individuals with type 1 diabetes 101±35 [pmol O₂] s⁻¹ mg⁻¹; control individuals 99±23 [pmol O₂] s⁻¹ mg⁻¹, <i>p</i>=0.82) did not differ between groups. Both intermyofibrillar (individuals with type 1 diabetes 6.07±2.16%; control individuals 6.01±1.11%; <i>p</i>=0.92) and subsarcolemmal (individuals with type 1 diabetes 18.70±8.16%; control individuals 19.29±7.36%; <i>p</i>=0.83) mitochondrial densities were not different between groups. Mitochondrial respiration normalised by density did not differ between groups. However, individuals with type 1 diabetes and higher HbA_1c displayed lower rates of mitochondrial respiration than those with lower HbA_1c, whereas those with higher BMI displayed lower mitochondrial densities than those with lower BMI.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Collectively, our study demonstrates that when matched for age, sex, BMI and <span>(dot{V}{text{O}}_{text{2max}})</span>, maximal muscle mitochondrial respiration and morphology in people with type 1 diabetes are not impaired. These findings highlight the importance of habitual exercise, optimal glucose management and a healthy BMI in maintaining mitochondrial health in individuals with type 1 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"25 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of lipotoxic hepatocyte-derived extracellular vesicles in pancreas inflammation: essential role of macrophage TLR4 in beta cell functionality.","authors":"Rosa Alén,Irma Garcia-Martinez,Nadia Cobo-Vuilleumier,Elisa Fernández-Millán,Paula Gallardo-Villanueva,Vitor Ferreira,Manuel Izquierdo,María Ángeles Moro,Ignacio Lizasoain,Natalia Nieto,Benoit R Gauthier,Ángela M Valverde","doi":"10.1007/s00125-025-06445-z","DOIUrl":"https://doi.org/10.1007/s00125-025-06445-z","url":null,"abstract":"AIMS/HYPOTHESISMetabolic dysfunction-associated steatotic liver disease (MASLD) is a common feature of obesity and type 2 diabetes. Under lipotoxic stress, hepatocytes release small extracellular vesicles (sEVs) which act locally and contribute to MASLD progression, but their role in beta cell function and development of type 2 diabetes remains largely unexplored. We aimed to examine whether hepatocyte-derived sEVs (Hep-sEVs) under lipotoxic conditions impact on liver and pancreas inflammation and subsequent effects on beta cell function.METHODSPrimary mouse hepatocytes and Huh7 human hepatocytes were treated with palmitic acid and Hep-sEVs were purified from the culture medium by differential ultracentrifugation. In vitro and in vivo approaches were used to decipher the role of Hep-sEVs in liver and pancreas inflammation and beta cell dysfunction in mouse and human pancreatic islets. The contribution of the Toll-like receptor 4 (TLR4) to Hep-sEV-mediated effects was investigated in pancreatic islets from myeloid-specific TLR4-deficient mice.RESULTSLipotoxic Hep-sEVs targeted pancreatic islet macrophages and induced TLR4-mediated inflammation. The subsequent inflammatory response downregulated beta cell identity genes and impaired glucose-stimulated insulin secretion in both INS-1 beta cells (p<0.05) and isolated pancreatic islets from mice (p<0.01) and humans (p<0.05). Specific deletion of TLR4 in macrophages protected pancreatic islets against inflammation and the impairment of glucose-stimulated insulin secretion induced by lipotoxic Hep-sEVs. Chronic administration of lipotoxic Hep-sEVs in lean mice induced liver and pancreas inflammation through the recruitment of immune cells. This intervention induced hepatocyte injury and fibrotic damage together with detrimental immunometabolic systemic effects. Insulin resistance in hepatocytes (p<0.01) and a compensatory insulin secretion (p<0.001) that prevented glucose intolerance were also observed in mice treated with lipotoxic Hep-sEVs.CONCLUSIONS/INTERPRETATIONThis study has provided evidence of liver and pancreas inflammation and beta cell dysfunction induced by lipotoxic Hep-sEVs. Our data also envision TLR4-mediated signalling in islet macrophages as a key mediator of the effects of lipotoxic Hep-sEVs on beta cell function.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"17 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proinflammatory cytokine-induced alpha cell impairment in human islet microtissues is partially restored by dual incretin receptor agonism","authors":"Kristine Henriksen, Chantal Rufer, Alexandra C. Title, Sayro Jawurek, Bolette Hartmann, Jens J. Holst, Filip K. Knop, Burcak Yesildag, Joachim Størling","doi":"10.1007/s00125-025-06425-3","DOIUrl":"https://doi.org/10.1007/s00125-025-06425-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>In type 1 diabetes, the counterregulatory glucagon response to low plasma glucose is impaired. The resulting increased risk of hypoglycaemia necessitates novel strategies to ameliorate alpha cell impairment. Here, we aimed to establish an in vitro type 1 diabetes-like model of alpha cell impairment using standardised reaggregated human islet microtissues (MTs) exposed to proinflammatory cytokines. Additionally, we investigated the therapeutic potential of incretin receptor agonists in improving alpha cell responses to low glucose.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Human islet MTs were exposed to proinflammatory cytokines (IL-1β, IFN-γ and TNF-α) for 1 day (short-term) and 6 days (long-term). Alpha cell function was assessed by sequential glucose-dependent secretion assays at 2.8 and 16.7 mmol/l glucose, followed by glucagon measurements. Additional evaluations included ATP content, caspase-3/7 activity, chemokine secretion and content of islet transcription factors (aristaless-related homeobox [ARX] and NK6 homeobox 1 [NKX6.1]) and hormones. The effects of incretin receptor agonist treatment (glucose-dependent insulinotropic polypeptide [GIP] analogue [<span>d</span>-Ala²]-GIP with or without the glucagon-like peptide 1 [GLP-1] receptor agonist liraglutide) alongside or after cytokine exposure were also investigated, focusing on low-glucose-dependent glucagon secretion.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Short-term cytokine exposure increased glucagon secretion at both 2.8 and 16.7 mmol/l glucose in islet MTs. In contrast, long-term cytokine exposure caused dose-dependent suppression of glucagon secretion at 2.8 mmol/l glucose, resembling a type 1 diabetes phenotype. Long-term cytokine exposure also diminished insulin and somatostatin secretion, reduced ATP content, increased caspase 3/7 activity and decreased islet content of ARX, NKX6.1, glucagon and insulin. Despite cytokine-induced impairment, alpha cells partially retained secretory capacity to <span>l</span>-arginine stimulation. Treatment with incretin receptor agonists during long-term cytokine exposure did not prevent alpha cell impairment. However, acute treatment with [<span>d</span>-Ala²]-GIP with or without liraglutide, or with the single-molecule dual agonist tirzepatide, after cytokine exposure partially restored glucagon secretion at low glucose.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Long-term cytokine exposure of human islet MTs created a type 1 diabetes-like phenotype with impaired low-glucose-induced glucagon secretion. This cytokine-induced alpha cell impairment was partially restored by [<span>d</span>-Ala²]-GIP with or without liraglutide, or by tirzepatide.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"38 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 1 diabetes prediction in autoantibody-positive individuals: performance, time and money matter","authors":"Lauric A. Ferrat, Erin L. Templeman, Andrea K. Steck, Hemang M. Parikh, Lu You, Suna Onengut-Gumuscu, Peter A. Gottlieb, Taylor M. Triolo, Stephen S. Rich, Jeffrey Krischer, R. Brett McQueen, Richard A. Oram, Maria J. Redondo","doi":"10.1007/s00125-025-06434-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06434-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Efficient prediction of clinical type 1 diabetes is important for risk stratification and monitoring of autoantibody-positive individuals. In this study, we compared type 1 diabetes predictive models for predictive performance, cost and participant time needed for testing.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We developed 1943 predictive models using a Cox model based on a type 1 diabetes genetic risk score (GRS2), autoantibody count and types, BMI, age, self-reported gender and OGTT-derived glucose and C-peptide measures. We trained and validated the models using halves of a dataset comprising autoantibody-positive first-degree relatives of individuals with type 1 diabetes (<i>n</i>=3967, 49% female, 14.9 ± 12.1 years of age) from the TrialNet Pathway to Prevention study. The median duration of follow-up was 4.7 years (IQR 2.0–8.1), and 1311 participants developed clinical type 1 diabetes. Models were compared for predictive performances, estimated cost and participant time.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Models that included metabolic measures had best performance, with most exhibiting small performance differences (less than 3% and <i>p</i>&gt;0.05). However, the cost and participant time associated with measuring metabolic variables ranged between US$56 and US$293 and 10–165 min, respectively. The predictive model performance had temporal variability, with the highest GRS2 influence and discriminative power being exhibited in the earliest preclinical stages. OGTT-derived metabolic measures had a similar performance to HbA_1c- or Index₆₀-derived models, with an important difference in cost and participant time.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Cost–performance model analyses identified trade-offs between cost and performance models, and identified cost-minimising options to tailor risk-screening strategies.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"50 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time in tight range and time in range for predicting the achievement of typical glucose management indicator and HbA1c targets.","authors":"Seohyun Kim,Sang Ho Park,Jin A Lee,So Hyun Cho,Rosa Oh,Ji Yoon Kim,You-Bin Lee,Gyuri Kim,Kyu Yeon Hur,Jae Hyeon Kim,Sang-Man Jin","doi":"10.1007/s00125-025-06442-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06442-2","url":null,"abstract":"AIMS/HYPOTHESISThis study aimed to compare the ability of time in tight range (TITR) and time in range (TIR) to predict the achievement of typical glucose management indicator (GMI) and HbA1c targets.METHODSThis cross-sectional analysis included 773 adults with diabetes receiving insulin therapy who visited Samsung Medical Center between June 2019 and December 2023 and wore a Dexcom G6 or FreeStyle Libre continuous glucose monitor for at least 90 days (sensor wear time, ≥70%). A receiver operating characteristic analysis was used to compare the ability of TITR and TIR to predict GMI and HbA1c targets.RESULTSTITR had significantly greater AUC values than TIR for predicting GMIs of <53 mmol/mol (7.0%) and <48 mmol/mol (6.5%) among participants using a Dexcom G6 or FreeStyle Libre continuous glucose monitor. TITR also had significantly greater AUC values than TIR for predicting HbA1c levels of <53 mmol/mol (7.0%) (95% CI for difference: 0.006, 0.03) and <48 mmol/mol (6.5%) (95% CI for difference: 0.001, 0.03) among participants using the FreeStyle Libre. In the HbA1c range of 48-53 mmol/mol (6.5-7.0%), TIR exhibited broader variations than TITR across CV groups. The modifying effect of CV on the association between TITR and GMI or HbA1c was minimised around a GMI and HbA1c level of 53 mmol/mol (7.0%).CONCLUSIONS/INTERPRETATIONTITR might be a more useful indicator than TIR of the achievement of typical GMI and HbA1c targets among adults with diabetes on insulin therapy.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"65 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial","authors":"Ildiko Lingvay, Malik Benamar, Liming Chen, Ariel Fu, Esteban Jódar, Tomoyuki Nishida, Jean-Pierre Riveline, Daisuke Yabe, Thomas Zueger, Rosângela Réa","doi":"10.1007/s00125-025-06435-1","DOIUrl":"https://doi.org/10.1007/s00125-025-06435-1","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"6 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up Front","authors":"","doi":"10.1007/s00125-025-06444-0","DOIUrl":"https://doi.org/10.1007/s00125-025-06444-0","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"139 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment discontinuation among users of GLP-1 receptor agonists and SGLT2 inhibitors in a national population of individuals with type 2 diabetes","authors":"Carl-Emil Lim, Björn Pasternak, Björn Eliasson, Peter Ueda","doi":"10.1007/s00125-025-06439-x","DOIUrl":"https://doi.org/10.1007/s00125-025-06439-x","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Aims/hypothesis&lt;/h3&gt;&lt;p&gt;Our aim was to assess treatment discontinuation, reinitiation and switching between drugs within the same drug class for glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors in individuals with type 2 diabetes.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;We used data from nationwide registers in Sweden to perform separate analyses for all patients with type 2 diabetes who filled a first prescription of a GLP-1 receptor agonist or an SGLT2 inhibitor between 2017 and 2021. Patients were considered to be on treatment for the period during which prescriptions were refilled before the estimated end date of the most recent prescription, including a 90-day grace period, i.e. the time allowed between and after prescriptions before treatment is considered as discontinued. We used the Aalen–Johansen estimator to estimate cumulative incidences of discontinuation and reinitiation, and Fine–Gray sub-distribution hazard models to assess the association of clinical variables with the risk of discontinuation.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Among 73,895 new users of GLP-1 receptor agonists, the cumulative incidence of treatment discontinuation was 23.6% at 1 year and 38.5% at 3 years. Among patients who discontinued, the cumulative incidence of treatment reinitiation was 41.1% at 1 year and 57.4% at 3 years after discontinuation. Among 113,207 new users of SGLT2 inhibitors, the cumulative incidence of treatment discontinuation was 27.9% at 1 year and 45.9% at 3 years, with a cumulative incidence of reinitiation of 40.4% at 1 year and 55.7% at 3 years after discontinuation. When varying the grace period between 60 days and 365 days, treatment discontinuation rates at 3 years ranged from 23.3% to 43.6% among GLP-1 receptor agonist users and from 28.8% to 50.6% among SGLT2 inhibitor users. The proportion of patients who had ongoing treatment, regardless of previous discontinuation episodes, ranged between approximately 70% and 80% for both drugs during a 1–5 year period after treatment initiation across analyses using various grace periods. In terms of switching, 22.9% of the GLP-1 receptor agonist users and 2.1% of the SGLT2 inhibitor users switched between drugs within the same drug class. Patient characteristics associated with treatment discontinuation were similar for GLP-1 receptor agonists and SGLT2 inhibitors, although the association between higher BMI and a lower likelihood of treatment discontinuation was stronger for GLP-1 receptor agonists.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions/interpretation&lt;/h3&gt;&lt;p&gt;Approximately half of type 2 diabetes patients who had started using GLP-1 receptor agonists or SGLT2 inhibitors had discontinued treatment within 5 years of follow-up. However, more than half of those who discontinued treatment subsequently reinitiated treatment, such that the proportion with ongoing","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"15 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}