Diabetes, Obesity & Metabolism最新文献

{"title":"Evaluation of the analytical and clinical accuracy of four blood glucose meters in pregnant women with hyperglycaemia.","authors":"Jincy Immanuel, Tobias Kongbrailatpam, Rohit Rajagopal, David Simmons","doi":"10.1111/dom.16209","DOIUrl":"https://doi.org/10.1111/dom.16209","url":null,"abstract":"<p><strong>Aims: </strong>Physiological changes during pregnancy can infuence the performance of blood glucose meters. This study aimed to evaluate the analytical and clinical accuracy of glucose meters in pregnant women with hyperglycaemia.</p><p><strong>Materials and methods: </strong>Glucose was measured by four commonly used meters among consecutive women with diabetes in pregnancy. Capillary and venous samples were collected concurrently and compared with i-STAT (amperometry) and laboratory (hexokinase) glucose as reference methods. Bland-Altman plot, International Organization for Standardization criteria, surveillance error grid (SEG) and haematocrit influence were assessed.</p><p><strong>Results: </strong>In total, 824 paired samples from 103 women were analysed (GDM 57%, mean i-STAT capillary glucose 6.7 ± 2.3 mmol/L [121 ± 41 mg/dL], laboratory glucose 6.6 ± 2.4 mmol/L [119 ± 43 mg/dL], median haematocrit 0.36 L/L). Mean capillary glucose measured on all meters was significantly different from that measured on i-STAT (all p < 0.001), whereas venous glucose measured on Contour Next, Accu-Chek Guide and the laboratory (plasma) was similar. Contour Next had the lowest bias when using both reference methods (mean bias [95% limits of agreement] meter vs. i-STAT: Contour Next 1.3% [-8% to 10.6%], Accu-Chek Guide -3.2% [-11.4% to 5%], FreeStyle Optium Neo -11.9% [-24.7% to 0.8%] and LifeSmart 6.8% [-5.8% to 19.4%]; meter versus laboratory: -0.2% [-8.1% to 7.7%], -0.2% [-10.2% to 9.8%], -3.8% [-17.6% to 10%] and 6.1% [-5.9% to 18.2%]), respectively. Only Contour Next and Accu-Chek Guide had ≥97% of pairs within the SEG no-risk zone during both comparisons. Meters did not show haematocrit-related bias.</p><p><strong>Conclusions: </strong>Accuracy of meters was higher when using venous samples than when using capillary samples. Contour Next and Accu-Chek Guide meters met accuracy standards in all analyses.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follistatins, activins and inhibins during osteoporosis therapy with denosumab or zoledronate and after their discontinuation.","authors":"Athanasios D Anastasilakis, Polyzois Makras, Stergios A Polyzos, Ajay Kumar, Bhanu Kalra, Christos S Mantzoros","doi":"10.1111/dom.16208","DOIUrl":"https://doi.org/10.1111/dom.16208","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank.","authors":"Madeleine M E Hayman, Waneisha Jones, Alisha Aman, Joey Ward, Jana Anderson, Donald M Lyall, Jill P Pell, Naveed Sattar, Paul Welsh, Rona J Strawbridge","doi":"10.1111/dom.16178","DOIUrl":"https://doi.org/10.1111/dom.16178","url":null,"abstract":"<p><strong>Aims: </strong>Glucagon-like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off-target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill-health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank.</p><p><strong>Materials and methods: </strong>All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes. Linear or Logistic regression analyses (adjusted for age, sex, population structure and genotyping chip) were conducted separately in unrelated individuals of self-reported white British (N = 408 774), white European (N = 50 314), South Asian (N = 7667), multiple-ancestry groups (N = 10 437) or African-Caribbean (N = 7641) subsets. All ancestries were subsequently combined in an inverse variance-weighted fixed effects meta-analysis. Bonferroni correction for multiple testing was applied (for number of independent genetic variants).</p><p><strong>Results: </strong>Associations were identified between GLP1R variants and body mass index (BMI), blood pressure and type 2 diabetes in all ancestries. All ancestries except South Asian had significant MIH associations (mood instability: rs111265626-G, odds ratio [OR] 0.851 [confidence interval, CI 0.79-0.92], risk-taking behaviour: rs75408972-T, OR 1.05 [CI 1.03-1.08] or chronic pain: rs9296280-C, OR 0.645 [CI 0.54-0.78]). The trans-ancestry meta-analysis showed mainly consistent effect sizes and directions for metabolic traits, but discordant directions MIH associations. Only signals for chronic pain, stroke and BMI influenced expression of GLP1R.</p><p><strong>Conclusions: </strong>GLP1R variants have consistent cardiometabolic effects across ancestries, but effects on MIH phenotypes are more varied. Any observed behavioural changes with GLP1RA are likely not acting directly through GLP1R.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulative risk of diabetic foot complications in risk groups of type 1 and type 2 diabetes: Real-world evidence from a 22-year follow-up study.","authors":"Abhilasha Akerkar, Pernille F Rønn, Vanja Kosjerina, Christian Stevns Hansen, Adam Hulman, Frederik Persson, Anne Rasmussen, Peter Rossing, Tarunveer S Ahluwalia","doi":"10.1111/dom.16200","DOIUrl":"https://doi.org/10.1111/dom.16200","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP-1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose-escalation Phase I study.","authors":"Yuxin Fan, Jiandong Yuan, Lichun Dong, Chongjing Yu, Haifeng Ding, Daosheng Xie, Runfang Guan, Ruixia Li, Wenhong Zou, Shuxian Long, Jion Chen, Yu Huang, Mei Yang, Jianchang He, Weibo Wen","doi":"10.1111/dom.16203","DOIUrl":"https://doi.org/10.1111/dom.16203","url":null,"abstract":"<p><strong>Objective: </strong>Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.</p><p><strong>Methods: </strong>A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.5 mg) and once-weekly administration for 2 weeks to reach target doses (5, 10 and 15 mg) by titration.</p><p><strong>Results: </strong>A total of 40 volunteers received at least one dose of BGM0504 or placebo. The PK profile of BGM0504 was investigated over a wide dose range and supported once-weekly administration. It was observed that C_max and AUC of BGM0504 were linearly proportional to the dose from 2.5-15 mg. The change in body weight (%) from baseline in BGM0504 groups was greater than that in the placebo group, with -3.24%, -6.26%, -7.09% and - 8.30% in 2.5, 5, 10 and 15 mg groups, respectively, indicating a certain dose correlation. Meanwhile, the potential roles of BGM0504 in glycaemic control were also observed. The most frequent adverse events reported were gastrointestinal (vomiting, nausea, decreased appetite, diarrhoea and abdominal distension).</p><p><strong>Conclusion: </strong>BGM0504 was generally safe and well tolerated with favourable PK profile and potential role in weight loss was also confirmed. These findings support subsequent development of BGM0504 for type 2 diabetes mellitus (T2DM) and obesity.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Achievement of HbA1c and weight targets in adults with type 2 diabetes on once weekly injectable glucagon-like peptide-1 receptor agonist therapy in UK primary care: A retrospective, real-world study.","authors":"Kunal Gulati, Katrien Wijndaele, Joanne Webb, Lill-Brith von Arx, Monica Seif, Thomas Jennison, Antonia Geneidat, Rosie Wild, Robert Wood, Kamlesh Khunti","doi":"10.1111/dom.16201","DOIUrl":"https://doi.org/10.1111/dom.16201","url":null,"abstract":"<p><strong>Aims: </strong>Evaluate glycated haemoglobin (HbA1c) and weight changes after 6 months of once-weekly (QW) injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in UK primary care.</p><p><strong>Materials and methods: </strong>Retrospective, non-interventional study, using the Clinical Practice Research Datalink Aurum primary care database, identified adults with type 2 diabetes (T2D) newly initiating a QW injectable GLP-1 RA between January 2020 and November 2021. Dual primary outcomes were proportion of patients with (1) HbA1c < 7% (<53 mmol/mol) and (2) weight loss categories (from 0% to 15+%) after 6 months of continuous GLP-1 RA therapy.</p><p><strong>Results: </strong>The study cohort comprised 10 816 adults: mean ± standard deviation age 58.8 ± 11.4 years, baseline HbA1c 9.3% ± 1.7% (78.1 ± 18.6 mmol/mol) and body mass index 36.6 ± 7.2 kg/m². Of 5236 patients with data, 32.8% achieved HbA1c < 7% after 6 months; this proportion was higher for time since T2D diagnosis <5 years (34.1%) versus longer disease duration: ≥5-<10 years (28.0%), ≥10-<15 years (18.7%) and ≥15 years (19.3%). Of 3963 patients with weight data, 22.0% did not lose weight; 34.0%, 27.0%, 11.4% and 5.6% achieved weight reductions of >0%-<5%, ≥5%-<10%, ≥10%-<15% and ≥15%, respectively. No major differences in weight loss were observed by diabetes duration.</p><p><strong>Conclusions: </strong>Two thirds of T2D patients receiving QW injectable GLP-1 RA for 6 months did not attain target HbA1c < 7%, and less than half and one-quarter of patients achieved ≥5% and ≥10% weight loss, respectively. Results suggest an unmet need for better clinical management of T2D in UK primary care.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin modulates hepatic lipid metabolism through the proprotein convertase subtilisin/kexin type 9/low density lipoprotein receptor pathway.","authors":"Fengyuan Lu, En Li, Yifeng Gao, Yan Zhang, Lijuan Kong, Xiaoyu Yang","doi":"10.1111/dom.16202","DOIUrl":"https://doi.org/10.1111/dom.16202","url":null,"abstract":"<p><strong>Background: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is mainly secreted by the liver, and plays a crucial role in lipid metabolism disorder. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can regulate lipid metabolism through various pathways, including reducing visceral fat accumulation, modulating serum lipoprotein levels and alleviating hepatic steatosis. However, the specific regulatory mechanisms remain unclear.</p><p><strong>Methods: </strong>We built a model of glucose and lipid metabolism disorder in vivo and in vitro, and explored the regulatory mechanism of dapagliflozin in regulating liver lipid metabolism.</p><p><strong>Results: </strong>We found that the SGLT2i dapagliflozin significantly reduced serum levels of PCSK9, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) in high-fat diet (HFD)-fed mice, while also improving hepatic steatosis. In vitro studies confirmed that dapagliflozin increased LDL receptor (LDLR) expression in HepG2 cells, enhancing their ability to uptake LDL-C.</p><p><strong>Conclusions: </strong>Further mechanistic studies revealed that the hepatocyte nuclear factor-1-alpha (HNF1α)/PCSK9/LDLR signalling pathway may be involved in dapagliflozin's regulation of lipid metabolism homeostasis.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of glycaemic improvement in children and young adults with type 1 diabetes and very elevated HbA1c using the MiniMed 780G system.","authors":"Yongwen Zhou, Alisa Boucsein, Venus R Michaels, Madeleine K Gray, Craig Jefferies, Esko Wiltshire, Ryan G Paul, Amber Parry-Strong, Maheen Pasha, Goran Petrovski, Martin I de Bock, Benjamin J Wheeler","doi":"10.1111/dom.16210","DOIUrl":"https://doi.org/10.1111/dom.16210","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to identify key factors with the greatest influence on glycaemic outcomes in young individuals with type 1 diabetes (T1D) and very elevated glycaemia after 3 months of automated insulin delivery (AID).</p><p><strong>Materials and methods: </strong>Data were combined and analysed from two separate and previously published studies with similar inclusion criteria assessing AID (MiniMed 780G) efficacy among young individuals naïve to AID (aged 7-25 years) with glycated haemoglobin A1c (HbA1c) ≥69 mmol/mol (≥8.5%). Univariate and multivariate linear models were performed to explore factors leading to the greatest improvements in HbA1c and time in range 3.9-10.0 mmol/L (70-180 mg/dL; TIR).</p><p><strong>Results: </strong>A total of 99 young individuals (aged 17.3 ± 4.2 years; baseline HbA1c 92 ± 21 mmol/mol [10.6% ± 1.9%]) were included. After 3 months of AID use, HbA1c improved to 65 ± 16 mmol/mol (8.1% ± 1.5%) (-27 ± 23 mmol/mol; -2.5% ± 2.1% change), and TIR improved from 24.2% ± 13.5% to 58.4% ± 15.4% (p both <0.001). In the multivariate analysis, two key factors for both HbA1c and TIR improvement were identified: high baseline HbA1c (>100 mmol/mol [>11.0%]) and high time in automation mode (>80%), which led to decreased HbA1c by 27.0 mmol/mol (2.4%) and 14.2 mmol/mol (1.3%) and increased TIR by 6.1% and 11.1% (p all <0.05) respectively. Meal announcement frequency >3 times/day and glucose target of 5.5 mmol/L (100 mg/dL) also led to significant increases in TIR. No other factors, including age, prior use of multiple daily injection, ethnicity, gender and optimal active insulin time 2 h, contributed to statistically significant HbA1c or TIR improvement.</p><p><strong>Conclusions: </strong>In young individuals naive to AID, those with the highest baseline HbA1c and high percentage time in automation experience the greatest benefits after initiation of AID. Sociodemographic background and carbohydrate counting adherence/knowledge should not prevent or delay access to AID technology (ACTRN12621000556842 and ACTRN12622001454763).</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and effectiveness in an uncontrolled setting of glucagon-like-peptide-1 receptor agonists in patients with familial partial lipodystrophy: Real-life experience from a national reference network.","authors":"Sophie Lamothe, Ines Belalem, Marie-Christine Vantyghem, Estelle Nobecourt, Héléna Mosbah, Sophie Béliard, Brigitte Delemer, Hippolyte Dupuis, Paul Vandenbroere, Nicolas Scheyer, Chloé Amouyal, Samy Hadjadj, Sonja Janmaat, Corinne Vigouroux, Camille Vatier","doi":"10.1111/dom.16175","DOIUrl":"https://doi.org/10.1111/dom.16175","url":null,"abstract":"<p><strong>Aim: </strong>To describe the effects of Glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with familial partial lipodystrophy (FPLD) assessed in a real-life setting in a national reference network.</p><p><strong>Patients and methods: </strong>We retrospectively collected clinical and metabolic parameters in patients with FPLD in the French lipodystrophy reference network, who initiated GLP-1RA. Data were recorded before, at one-year (12 ± 6 months) and at the latest follow-up on GLP-1RA therapy (≥18 months).</p><p><strong>Results: </strong>Seventy-six patients (89.4% of women), diagnosed with LMNA-related FPLD2 (n = 57), PPARG-related FPLD3 (n = 4), PLIN1-related FPLD4 (n = 5) or FPLD1 (n = 10) initiated GLP-1RA therapy between 2008 and 2024. Patients were aged a median (IQR) 48 years (34.5-57), body mass index (BMI) was 26.0 kg/m² (23.9-29.5), HbA1c 8.3% (7.5-9.3), triglycerides 2.31 mmol/L (1.62-3.88). GLP-1RA were used in addition to previously used antidiabetics, 50% of patients being insulin-treated. After one year with GLP-1RA therapy, BMI, HbA1c and triglycerides significantly decreased to 25.6 kg/m² (22.7-29.1), 7.3% (6.6-8.3) and 1.97 mmol/L (1.5-3.2) respectively (p < 0.001, p < 0.001 and p < 0.01, respectively), without significant changes in other antidiabetic and lipid-lowering drugs. Gamma-glutamyl-transferase and alanine-aminotransferase levels also significantly decreased. Effects on HbA1c, BMI and triglycerides persisted in the long term. One case of acute pancreatitis occurred during follow-up, associated with severe hypertriglyceridemia in a non-observant patient. Gastrointestinal symptoms affected 34% of patients, leading to GLP-1RA withdrawal in six patients.</p><p><strong>Conclusion: </strong>GLP-1RA significantly improved BMI, HbA1c and triglycerides in a large majority of patients with FPLD. Larger and prospective controlled studies are warranted for identification of predictive factors and safety.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond glycated haemoglobin: Modelling contemporary management of type 2 diabetes with the updated Cardiff model.","authors":"Phil McEwan, Volker Foos, Geraint Roberts, Robert H Jenkins, Marc Evans, David C Wheeler, Jieling Chen","doi":"10.1111/dom.16141","DOIUrl":"https://doi.org/10.1111/dom.16141","url":null,"abstract":"<p><strong>Aims: </strong>Recommendations on the use of newer type 2 diabetes (T2D) treatments (e.g., SGLT2 inhibitors and GLP-1 receptor agonists [RA]) in contemporary clinical guidelines necessitate a change in how T2D models approach therapy selection and escalation. Dynamic, person-centric clinical decision-making considers factors beyond a patient's HbA1c and glycaemic targets, including cardiovascular (CV) risk, comorbidities and bodyweight. This study aimed to update the existing Cardiff T2D health economic model to reflect modern T2D management and to remain fit-for-purpose in supporting decision-making.</p><p><strong>Materials and methods: </strong>The Cardiff T2D model's therapy selection/escalation module was updated from a conventional, glucose-centric to a holistic approach. Risk factor progression equations were updated based on UKPDS90; the cardio-kidney-metabolic benefits of SGLT2i and GLP-1 RA were captured via novel risk equations derived from relevant outcomes trial data. The significance of the updates was illustrated by comparing predicted outcomes and costs for a newly diagnosed T2D population between conventional and holistic approaches to disease management, where the latter represents recent treatment guidelines.</p><p><strong>Results: </strong>A holistic approach to therapy selection/escalation enables early introduction of SGLT2i and GLP-1 RA in modelled pathways in a manner aligned to guidelines and primarily due to elevated CV risk. Compared with a conventional approach, only considering HbA1c, patients experience fewer clinical events and gain additional health benefits.</p><p><strong>Conclusions: </strong>Predictions based on a glucose-centric approach to therapy are likely to deviate from real-world observations. A holistic approach is more able to capture the nuances of contemporary clinical practice. T2D modelling must evolve to remain robust and relevant.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}