Medical Information, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
Intensive Care Unit and Department of Cardiology, Toranomon Hospital, Tokyo, Japan.
J Clin Pharmacol. 2022 Mar;62(3):366-375. doi: 10.1002/jcph.1970. Epub 2021 Nov 19.
Although sodium-glucose cotransporter 2 (SGLT2) inhibitors lower serum uric acid, their long-term effect on uric acid metabolism is not well understood. We analyzed pooled data from studies wherein patients with type 2 diabetes mellitus received luseogliflozin, an SGLT2 inhibitor. Upon stratifying patients by baseline glycated hemoglobin (HbA ) or serum uric acid, lower HbA or higher serum uric acid level was associated with a greater reduction in serum uric acid after treatment. At week 12 of treatment, significant increases in urinary glucose/creatinine (Cr) ratio and urinary uric acid clearance/Cr clearance ratio (C /C ratio) and a significant reduction in serum uric acid were observed. Comparison of the subgroups of patients with a reduction or an increase in serum uric acid showed that the increase subgroup had a higher estimated glomerular filtration rate (eGFR) at baseline, and the eGFR was significantly reduced, associated with a significant reduction in the C /C ratio. Multiple regression analysis showed that the reduction in serum uric acid in the luseogliflozin group was strongly associated with baseline high serum uric acid, low HbA levels, and an increase in eGFR. Luseogliflozin was shown to reduce serum uric acid by enhancing urinary uric acid excretion in association with increased urinary glucose. Treatment with luseogliflozin resulted in increased serum uric acid in some patients, which may be due to reduced glomerular filtration of uric acid via the tubuloglomerular feedback. SGLT2 inhibitors reduced serum uric acid desirably in patients with type 2 diabetes mellitus with low HbA and high serum uric acid.
尽管钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可降低血尿酸水平，但它们对尿酸代谢的长期影响尚不清楚。我们分析了接受 SGLT2 抑制剂芦格列净治疗的 2 型糖尿病患者的研究汇总数据。根据基线糖化血红蛋白（HbA ）或血清尿酸水平对患者进行分层后，发现较低的 HbA 或较高的血清尿酸水平与治疗后血清尿酸降低幅度更大相关。在治疗 12 周时，观察到尿葡萄糖/肌酐（Cr）比值和尿尿酸清除率/Cr 清除率比值（C/C 比值）显著升高，血清尿酸显著降低。比较血清尿酸降低或升高的患者亚组发现，尿酸升高亚组的基线估算肾小球滤过率（eGFR）较高，并且 eGFR 显著降低，与 C/C 比值显著降低相关。多元回归分析显示，芦格列净组血清尿酸降低与基线时高血清尿酸、低 HbA 水平和 eGFR 增加密切相关。芦格列净通过增强与尿糖增加相关的尿尿酸排泄来降低血清尿酸。在一些患者中，芦格列净治疗导致血清尿酸升高，这可能是由于肾小管-肾小球反馈导致尿酸肾小球滤过减少。SGLT2 抑制剂可降低 HbA 水平低和血清尿酸水平高的 2 型糖尿病患者的血清尿酸水平，这是理想的。
