Diabetes, Obesity & Metabolism最新文献

{"title":"Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach.","authors":"Alex E Henney, David R Riley, Megan Heague, Carl A Roberts, Theresa J Hydes, Matthew Anson, David M Hughes, Uazman Alam, Daniel J Cuthbertson","doi":"10.1111/dom.70169","DOIUrl":"https://doi.org/10.1111/dom.70169","url":null,"abstract":"<p><strong>Aims: </strong>There is growing evidence that the GLP-1 system is implicated in alcohol and other substance use disorders, and that GLP-1-based therapies may have therapeutic relevance in alcohol use disorder (AUD). We aimed to determine the impact of GLP-1 based therapies on incident AUDs in a real-world setting in patients with T2D.</p><p><strong>Material and methods: </strong>We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America. Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i). First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses. Four target trial cohorts were generated and compared with a reference arm of patients treated with DPP4i: cohort (1) treatment with tirzepatide; cohort (2) treatment with semaglutide; cohort (3) treatment with liraglutide; and cohort (4) treatment with dulaglutide. Cohorts underwent propensity score matching 1:1 for confounders. We examined rates of incident AUD (ICD-10 code F10) and performed head-to-head analyses of the incretin-based therapies. We also performed sensitivity analyses relating to whether treatment was adjunctive therapy with metformin and by treatment adherence.</p><p><strong>Results: </strong>After propensity-score matching, we identified four target trials of patients treated with tirzepatide (n = 7165), semaglutide (n = 20 198), liraglutide (n = 6565), and dulaglutide (n = 19 061); 1:1 with the reference (DPP4i) patients. Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively). Head-to-head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]).</p><p><strong>Conclusion: </strong>In patients with T2D, tirzepatide and semaglutide treatment is associated with a lower incidence of AUD; robust randomised, controlled evidence for the use of these drugs for this novel indication is appropriate.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243385","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":"Reevaluating the causal link between liver fat and hyperglycaemia.","authors":"Zhaoqian Xu, Qi Huang, Xinlei Zhang, Song Wang, Yingying Luo, Feng Liu, Linong Ji, Xiantong Zou","doi":"10.1111/dom.70178","DOIUrl":"https://doi.org/10.1111/dom.70178","url":null,"abstract":"<p><strong>Aims: </strong>Given the proposed role of liver fat in diabetes, this study examined its potential causal relationship with glycaemic traits.</p><p><strong>Materials and methods: </strong>A two-sample Mendelian randomisation (MR) analysis using genome-wide association study (GWAS) data from 37 358 individuals was conducted to evaluate the causal effect of liver fat on fasting glucose level, HbA1c level, postprandial glucose level, fasting insulin level, and homeostatic model assessment of insulin resistance (HOMA-IR). A meta-analysis of randomised controlled trials (RCTs) examining drugs that target hepatic steatosis and their effects on glycaemic traits was subsequently performed.</p><p><strong>Results: </strong>MR analysis revealed no causal effect of liver fat content on the following glycaemic traits: fasting glucose level (β = -0.006; p = 0.827), HbA1c level (β = -0.009; p = 0.366), postprandial glucose level (β = -0.063; p = 0.257), fasting insulin level (β = 0.010; p = 0.691), and HOMA-IR (β = 0.001; p = 0.965). In 13 RCTs of liver fat-targeted drugs (n = 2482), no significant differences were observed in the changes in fasting blood glucose (SMD: -0.09, 95% CI: -0.18 to 0.01) or HbA1c levels (SMD: -0.02, 95% CI: -0.12 to 0.07) between drug-treated patients and controls. Meta-regression analysis revealed no statistically significant linear relationship between liver fat reduction and changes in fasting blood glucose or HbA1c levels.</p><p><strong>Conclusion: </strong>The absence of a causal relationship between hepatic steatosis and glycaemic traits suggests that hyperglycaemia in metabolic dysfunction-associated steatotic liver disease may involve additional mechanisms beyond liver fat accumulation.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231137","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":"Should glycaemic variability and times spent in levels 1 and 2 hypoglycaemia be revised downward in type 1 diabetes treated with advanced systems of insulin delivery?","authors":"Louis Monnier, Claude Colette, Pierre-Yves Benhamou, David Owens","doi":"10.1111/dom.70179","DOIUrl":"https://doi.org/10.1111/dom.70179","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231157","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":"Efficacy and safety of once-weekly basal insulin therapy in people with type 1 diabetes: A systematic review and meta-analysis.","authors":"Ludovico Di Gioia, Sergio Di Molfetta, Irene Caruso, Mariangela Caporusso, Gian Pio Sorice, Angelo Cignarelli, Annalisa Natalicchio, Sebastio Perrini, Luigi Laviola, Francesco Giorgino","doi":"10.1111/dom.70176","DOIUrl":"https://doi.org/10.1111/dom.70176","url":null,"abstract":"<p><strong>Aims: </strong>Once-weekly basal insulins may offer similar or superior HbA1c reduction compared to once-daily analogues in people with type 1 or type 2 diabetes. However, concerns about hypoglycaemia persist in individuals on multiple daily injections. This meta-analysis (PROSPERO CRD42024606874) aimed to evaluate the efficacy and safety of once-weekly basal insulin therapy in type 1 diabetes.</p><p><strong>Materials and methods: </strong>A systematic search was conducted in MEDLINE, Web of Science and CENTRAL up to 1 April 2025. We included randomized controlled trials (RCTs) comparing insulin icodec or efsitora against once-daily basal insulins in people with type 1 diabetes. Three reviewers independently evaluated the retrieved citations. The primary outcome was the change in HbA1c. Meta-analysis was performed using fixed- or random-effects models based on heterogeneity.</p><p><strong>Results: </strong>Five RCTs were included, enrolling 1629 adults living with type 1 diabetes. Once-weekly and once-daily basal insulins had similar effects on HbA1c (high certainty), body weight (moderate certainty), time in range (moderate certainty) and time above range. However, safety concerns emerged due to increased rates of level 3 hypoglycaemia (incidence rate ratio 2.532, 95% confidence interval [CI] 1.758-3.645; moderate certainty). A significantly lower weekly bolus insulin dose was observed with once-weekly basal insulin therapy (estimated treatment ratio 0.837, 95% CI 0.794-0.882, I² = 0%; high certainty).</p><p><strong>Conclusions: </strong>This meta-analysis is the first to evaluate the efficacy and safety of once-weekly basal insulin therapy exclusively in adults with type 1 diabetes and including all published RCTs. The analysis demonstrated a similar glucose-lowering effect compared to once-daily basal insulin but revealed an increased occurrence of severe hypoglycaemia.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231043","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 reduces epicardial adipose tissue in patients with heart failure and type 2 diabetes.","authors":"Mohmmad Alghamdi, Adel Dihoum, Khalid Hakami, Atanu Bhattacharjee, Alexander J M Brown, Jagdeep Singh, Shaween Altalabany, Chim Lang, Ify Mordi, Faisel Khan","doi":"10.1111/dom.70164","DOIUrl":"https://doi.org/10.1111/dom.70164","url":null,"abstract":"<p><strong>Background: </strong>Epicardial adipose tissue (EAT) has a contributory role in the progression of heart failure. We tested whether dapagliflozin reduces EAT in adults with type 2 diabetes (T2D) and heart failure and explored links with systemic inflammation and cardiac structure.</p><p><strong>Methods: </strong>This analysis is based on pooled data from two phase 2, single-centre, double-blind, placebo-controlled randomised trials (REFORM and DAPA-LVH) conducted in Scotland. Exactly 122 participants with T2D and stage B or C heart failure were randomised to dapagliflozin 10 mg once daily or placebo for 12 months. Cardiac magnetic resonance imaging (CMR) was used to assess EAT. At baseline and follow-up, the inflammatory markers TNF, IL-1, IL-6, IL-10, and CRP were measured.</p><p><strong>Results: </strong>At baseline, obesity was common (75% with BMI ≥30 kg/m²) and heart-failure phenotypes were balanced (HFpEF 51%, HFrEF 49%). After 12 months, dapagliflozin significantly reduced EAT independently of changes in BMI (-1.16 ± 0.18 vs. +0.36 ± 0.19 cm², p < 0.001), BMI (-1.17 ± 0.16 vs. -0.18 ± 0.17 kg/m², p < 0.001), and left ventricular mass (-3.53 ± 1.77 vs. +1.57 ± 1.83 g, p = 0.048) compared with placebo.</p><p><strong>Conclusion: </strong>Dapagliflozin shrinks EAT and LV mass independently of BMI in T2D patients with stage B/C heart failure, supporting EAT as a modifiable target of SGLT2 inhibition. The absence of parallel changes in systemic inflammation suggests primarily local mechanisms.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237477","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":"Weight loss in people with type 1 diabetes over 12 months: Real-world data comparing tirzepatide, semaglutide and liraglutide.","authors":"Ebaa Al Ozairi, Mohammad Irshad, Jumana Alkandari, Litty Sojan, Dherar Alroudhan, Nourah Alotaibi, Carel W le Roux","doi":"10.1111/dom.70172","DOIUrl":"https://doi.org/10.1111/dom.70172","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to compare the effects of tirzepatide, semaglutide, and liraglutide on body weight and metabolic risk markers over 12 months in people with body mass index ≥27 kg/m² and type 1 diabetes (T1D).</p><p><strong>Methods: </strong>This real-world study included 250 people with obesity and T1D (female = 54.8%), treated with either tirzepatide (n = 35), semaglutide (n = 36), liraglutide (n = 97) or usual care (n = 82). Secondary outcomes included changes in lipid profile, renal and liver markers, blood pressure, and HbA1c.</p><p><strong>Results: </strong>All three agents led to significant weight loss. Tirzepatide showed the greatest reduction of weight loss (10.9%; p < 0.001), followed by semaglutide (9.9%; p < 0.001) and liraglutide (7.1%; p < 0.001). Dose-dependent reductions were observed for tirzepatide and semaglutide. Tirzepatide, semaglutide and liraglutide modestly reduced HbA1c by 0.65% (p = 0.004), 0.33% (p = 0.034) and 0.23% (p = 0.017), respectively. LDL-cholesterol was reduced by semaglutide (p = 0.05) and liraglutide (p = 0.02), and liraglutide also lowered the urine albumin-to-creatinine ratio (p = 0.007). There was no change in body weight and HbA1c in the usual care group. No severe hypoglycaemia or diabetic ketoacidosis (DKA) events were reported in any group.</p><p><strong>Conclusion: </strong>Tirzepatide, semaglutide, and liraglutide reduced bodyweight and improved in selected metabolic risk markers over 12 months without increasing the risk for hypoglycaemia or DKA. Weight loss appeared less compared with patients without diabetes. Tirzepatide, semaglutide and liraglutide modestly improved glycaemic control in adults with T1D and obesity. These findings support the potential adjunctive role of GLP-1 receptor agonists in people with obesity and T1D and underscore the need for further validation through randomized controlled trials.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231168","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":"AdipoRon exerts divergent effects on hepatic and bone metabolism.","authors":"Stergios A Polyzos, Jannis Kountouras","doi":"10.1111/dom.70190","DOIUrl":"https://doi.org/10.1111/dom.70190","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231098","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":"Addressing unmet needs for chronic kidney disease treatment in type 1 diabetes: A review.","authors":"Katherine R Tuttle, Linong Ji, Chantal Mathieu, Jonathan Rosen","doi":"10.1111/dom.70180","DOIUrl":"https://doi.org/10.1111/dom.70180","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a serious complication occurring in nearly one of three people with type 1 diabetes (T1D). Major therapeutic advances have been made in the management of CKD for people with type 2 diabetes (T2D), thereby improving their kidney, cardiovascular, and survival outcomes. However, people with T1D were largely excluded from these CKD therapeutic development programmes. Recent treatment advancements for people with T2D include the introduction of sodium-glucose cotransporter 2 inhibitors, a nonsteroidal mineralocorticoid antagonist, and glucagon-like peptide-1 receptor agonists. The development and progression of CKD in people with T1D are driven by a constellation of risk factors such as hyperglycemia, hypertension, obesity, and others that share common mechanistic links with T2D. As such, a compelling rationale exists for focused studies of these therapeutic classes for the treatment of CKD in T1D. Additionally, care provided by a coordinated team of primary care clinicians, endocrinologists, nephrologists, and cardiologists is central to therapeutic implementation. There is a major unmet need for improved treatments for CKD in people with T1D. Ongoing and future studies will help to establish whether proven therapies for CKD in T2D are also safe and efficacious in people with T1D. Coordinated, cross-specialty approaches to awareness, detection, and intervention for CKD are also needed to improve kidney, cardiovascular, and survival outcomes in people with T1D.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237500","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":"Repurposing colchicine for reduction of residual inflammatory risk in type 1 diabetes: Design and rationale of the REC1TE trial.","authors":"David S Mathiesen, Josefine V Hansen, Aske Høck, Casper K Nielsen, Miriam G Pedersen, Peter L Kristensen, Henrik U Andersen, Marie Louise Aarestrup, Julie L Forman, Jonatan I Bagger, Thomas F Dejgaard, Filip K Knop, Nicklas J Johansen, Asger B Lund","doi":"10.1111/dom.70139","DOIUrl":"https://doi.org/10.1111/dom.70139","url":null,"abstract":"<p><strong>Aims: </strong>Compared to people without diabetes, individuals with type 1 diabetes have a several-fold increased risk of cardiovascular (CV) morbidity and mortality despite guideline-recommended management of traditional risk factors; so-called residual CV risk. Systemic low-grade inflammation has emerged as an independent risk factor for CV events with residual inflammatory risk referring to the increased risk conferred by inflammation when all other risk factors are well-treated. Several clinical trials in individuals without type 1 diabetes have demonstrated improved CV outcomes when targeting residual inflammatory risk with anti-inflammatory therapies, of which especially low-dose colchicine has shown promise and has been approved by the FDA for atherosclerotic CV disease (CVD) prevention.</p><p><strong>Materials and methods: </strong>This trial is an investigator-initiated, randomised, double-blind, placebo-controlled phase 2b trial evaluating low-dose colchicine (0.5 mg/day) in individuals with type 1 diabetes, established or high risk of atherosclerotic CVD and residual inflammatory risk (defined as two consecutive measurements of high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L). A total of 102 participants have been included in the trial and randomly assigned to colchicine or placebo (1:1) for up to 52 weeks in addition to standard of care. The primary endpoint is the difference in hsCRP at week 26. Recruitment began August 2023 and last patient last visit is expected in February 2026.</p><p><strong>Results and conclusions: </strong>Here, we present the protocol for a study designed to evaluate the efficacy of low-dose colchicine on residual inflammatory risk in individuals with type 1 diabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231128","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":"Postoperative insulin requirements in surgical patients receiving fully automated insulin delivery in the hospital.","authors":"Gabija Krutkyte, Clara Escorihuela-Altaba, Michael S Hughes, Christos T Nakas, David Herzig, Lia Bally","doi":"10.1111/dom.70170","DOIUrl":"https://doi.org/10.1111/dom.70170","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231036","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}