Factors Influencing Change in Serum Uric Acid After Administration of the Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin in Patients With Type 2 Diabetes Mellitus

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(1c)) or serum uric acid, lower HbA(1c) 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-UA/C-Cr 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-UA/C-Cr 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(1c) 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(1c) and high serum uric acid.