Febuxostat Improves Postprandial Glucose Regulation and Insulin Sensitivity in Hyperuricemic Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes: A Prospective Cohort Study.
Shuang Liu, Qingsong Liu, Ronger Gu, Mian Wu, Shuo Meng, Le Yan, Qi Chen, Cuiling Zhu, Si Chen, Bei Xu, Fengjing Liu, Haibing Chen
{"title":"Febuxostat Improves Postprandial Glucose Regulation and Insulin Sensitivity in Hyperuricemic Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes: A Prospective Cohort Study.","authors":"Shuang Liu, Qingsong Liu, Ronger Gu, Mian Wu, Shuo Meng, Le Yan, Qi Chen, Cuiling Zhu, Si Chen, Bei Xu, Fengjing Liu, Haibing Chen","doi":"10.2147/DDDT.S522154","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemia (HUA) has been linked to an elevated risk of impaired glucose metabolism. This study aimed to investigated the impact of the urate-lowering drug febuxostat on blood glucose levels, insulin sensitivity, and β-cell function in subjects with HUA who present with normoglycemia, prediabetes, or newly diagnosed type 2 diabetes (T2DM).</p><p><strong>Methods: </strong>We assessed the glucose metabolism of participants with HUA using a 3-h oral glucose tolerance test (OGTT). Participants were categorized into two groups: those with HUA and normal glucose metabolism (NGM, n=28), and those with HUA and abnormal glucose metabolism (AbGM, n=32), including prediabetes (n=20) and newly diagnosed T2DM (n=12). Both groups received a daily dose of 40 mg febuxostat for 24 consecutive weeks and underwent 3-h OGTT at 12 and 24 weeks. Glucose, insulin, and C-peptide were measured to calculate insulin sensitivity (Stumvoll index, Gutt index) and β-cell function (Insulin Secretion-Sensitivity Index-2 and Disposition Index) indices. Differences in glucose levels and indices were analyzed by repeated measures ANOVA including interaction terms between groups and the time of visit.</p><p><strong>Results: </strong>After 24 weeks of febuxostat treatment, subjects with HUA and AbGM showed significant reductions in postprandial 1-h (11.88±1.39mmol/L at baseline, 10.97±2.74mmol/L at 12 weeks, and 11.12±1.92mmol/L at 24 weeks, Ptime=0.031) and 2-h glucose (10.25±1.71mmol/L at baseline, 9.39±2.77mmol/L at 12 weeks, and 9.16±2.67mmol/L at 24 weeks, Ptime=0.014). Febuxostat significantly improved insulin sensitivity of subjects in the AbGM group, but did not affect β-cell function. Moreover, the improvement in insulin sensitivity in these subjects was not directly correlated with the improvement in uric acid. No significant changes were observed in subjects with NGM.</p><p><strong>Conclusion: </strong>In subjects with HUA and prediabetes or newly diagnosed T2DM, febuxostat significantly enhanced postprandial glucose and insulin sensitivity, though it did not notably improve β-cell function. Further research is required to explore how febuxostat enhances insulin sensitivity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4875-4884"},"PeriodicalIF":4.7000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148943/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S522154","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Hyperuricemia (HUA) has been linked to an elevated risk of impaired glucose metabolism. This study aimed to investigated the impact of the urate-lowering drug febuxostat on blood glucose levels, insulin sensitivity, and β-cell function in subjects with HUA who present with normoglycemia, prediabetes, or newly diagnosed type 2 diabetes (T2DM).
Methods: We assessed the glucose metabolism of participants with HUA using a 3-h oral glucose tolerance test (OGTT). Participants were categorized into two groups: those with HUA and normal glucose metabolism (NGM, n=28), and those with HUA and abnormal glucose metabolism (AbGM, n=32), including prediabetes (n=20) and newly diagnosed T2DM (n=12). Both groups received a daily dose of 40 mg febuxostat for 24 consecutive weeks and underwent 3-h OGTT at 12 and 24 weeks. Glucose, insulin, and C-peptide were measured to calculate insulin sensitivity (Stumvoll index, Gutt index) and β-cell function (Insulin Secretion-Sensitivity Index-2 and Disposition Index) indices. Differences in glucose levels and indices were analyzed by repeated measures ANOVA including interaction terms between groups and the time of visit.
Results: After 24 weeks of febuxostat treatment, subjects with HUA and AbGM showed significant reductions in postprandial 1-h (11.88±1.39mmol/L at baseline, 10.97±2.74mmol/L at 12 weeks, and 11.12±1.92mmol/L at 24 weeks, Ptime=0.031) and 2-h glucose (10.25±1.71mmol/L at baseline, 9.39±2.77mmol/L at 12 weeks, and 9.16±2.67mmol/L at 24 weeks, Ptime=0.014). Febuxostat significantly improved insulin sensitivity of subjects in the AbGM group, but did not affect β-cell function. Moreover, the improvement in insulin sensitivity in these subjects was not directly correlated with the improvement in uric acid. No significant changes were observed in subjects with NGM.
Conclusion: In subjects with HUA and prediabetes or newly diagnosed T2DM, febuxostat significantly enhanced postprandial glucose and insulin sensitivity, though it did not notably improve β-cell function. Further research is required to explore how febuxostat enhances insulin sensitivity.
期刊介绍:
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.