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 work

Correspondence: Fengjing Liu, Email liufengjing@shsmu.edu.cn Haibing Chen, Email hbchen@tongji.edu.cn

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.

Keywords: type 2 diabetes, prediabetes, hyperuricemia, insulin sensitivity, β-cell function