Associations between urate-lowering therapy and the risk of type 2 diabetes mellitus

Abstract

Background Gout is independently associated with increased risk of type 2 diabetes mellitus (T2DM). Urate-lowering therapy (ULT) might be beneficial in lowering the risks of T2DM. Therefore, we conducted a nested case-control study to evaluate the associations between ULT and T2DM. Methods This study retrieved the data of 29,765 gout patients from the period of 1998–2010 by using data from Taiwan’s National Health Insurance Research Database. Controls (n = 59,530) were matched at a 1:2 ratio by age, sex, and region. Multivariate Cox proportional hazards regression were performed to examine the dose-dependent relationship between ULT and T2DM. Results The adjusted Hazard ratio (HR) for the association of T2DM with allopurinol or benzbromarone exposure was 1.17 (95% confidence interval (CI) 1.07–1.28) and1.09 (95% CI 1.03–1.15), respectively. The HR for the cumulative allopurinol dose was 0.87 (95% CI 0.71–1.07) for patients with dose 1.3 mg/day and was 1.31 (95% CI 1.13–1.52) for those with a dose >15.2 mg/day. Similarly, the HR for the cumulative benzbromarone dose was 0.85 (95% CI 0.75–0.96) for patients with a dose 1.3 mg/day and 1.42 (95% CI 1.30–1.55) for patients with a dose>9.4 mg/day, respectively. Moreover, the average exposure dose of >100 mg/day for allopurinol and >100 mg/day for benzbromarone was associated with a 1.28-fold (95% CI 1.11–1.48) and 1.47-fold (95% CI 1.23–1.76) T2DM risk respectively. The HR for patients in aged >50 years group with cumulative dose 1.3 mg/day of allopurinol or benzbromarone had lower risk of T2DM (HR = 0.74, 95% CI 0.58–0.94 for allopurinol; HR = 0.79, 95% CI 0.69–0.90 for benzbromarone). Conclusion Gout patients with prolonged ULT and a high dose of ULT were associated with a significant increase in T2DM risk. Although gout patients with age greater than 50 years and a lower dose of ULT may be beneficial in lowering T2DM risk, further clinical studies need to be confirmed these associations.