Drug Design, Development and Therapy (Jun 2025)

Febuxostat Improves Postprandial Glucose Regulation and Insulin Sensitivity in Hyperuricemic Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes: A Prospective Cohort Study

  • Liu S,
  • Liu Q,
  • Gu R,
  • Wu M,
  • Meng S,
  • Yan L,
  • Chen Q,
  • Zhu C,
  • Chen S,
  • Xu B,
  • Liu F,
  • Chen H

Journal volume & issue
Vol. Volume 19, no. Issue 1
pp. 4875 – 4884

Abstract

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Shuang Liu,1,* Qingsong Liu,2,* Ronger Gu,1 Mian Wu,3 Shuo Meng,1 Le Yan,1 Qi Chen,1 Cuiling Zhu,1 Si Chen,4 Bei Xu,1,* Fengjing Liu,4,* Haibing Chen1,* 1Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmacy, Heze Municipal hospital, Heze, People’s Republic of China; 3Department of Endocrinology and Metabolism, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 4Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengjing Liu, Email [email protected] Haibing Chen, Email [email protected]: 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.Keywords: type 2 diabetes, prediabetes, hyperuricemia, insulin sensitivity, β-cell function

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