Sodium-Glucose Cotransporter-2 Inhibitor Immediately Decreases Serum Uric Acid Levels in Type 2 Diabetic Patients

Abstract

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new antihyperglycemic drugs for type 2 diabetes. SGLT2 inhibitors ameliorate cardiovascular morbidity and mortality as well as kidney disease progression by reducing body weight (BW), blood pressure (BP), visceral adiposity, albuminuria, and serum uric acid and blood glucose levels. However, it is not clear which effects are pronounced, and what mechanisms are associated with these effects. Material/Methods This study recruited patients with type 2 diabetes who were prescribed an SGLT2 inhibitor for the first time in our outpatient department. Clinical parameters were measured before and 6 months after the administration of the SGLT2 inhibitor, without the addition of new drugs and dose changes for all prescribed drugs. Results This study recruited 24 patients with type 2 diabetes. No significant differences in BP, glycated hemoglobin (HbA1c) levels, and low-density lipoprotein cholesterol levels were observed after SGLT2 inhibitor administration. In contrast, BW and serum uric acid levels decreased significantly, and the fractional excretion of uric acid (FEUA) increased significantly after administration. While no significant relationships were observed between serum uric acid and FEUA with respect to the percentage changes from baseline values, the percentage changes in serum uric acid levels from baseline were significantly and positively associated with those in serum creatinine levels. Conclusions Serum uric acid levels were immediately decreased owing to the administration of SGLT2 inhibitor, but BP, blood glucose, and serum lipid levels were unchanged. These changes in serum uric acid levels may be associated with changes in renal function.

The effect of dapagliflozin on uric acid excretion and serum uric acid level in advanced CKD

“…Similar to our result, previous studies have shown that SGLT2i increase FEUA and decrease serum UA levels in patients with type 2 DM 14 – 17 . Ohashi et al reported that SGLT2i increased FEUA (before administration; 5.98 ± 2.59% vs. after administration; 7.71 ± 3.22%) and reduce serum UA levels (before administration; 6.13 ± 1.36 mg/dL vs. after administration; 5.20 ± 1.11 mg/dL) in patients with type 2 DM whose eGFR was 63.25 ± 24.66 mL/min/1.73 m 2 17 .…”

“…On the other hand, allopurinol did not improve renal outcomes 12 , 13 . One of the pleiotropic effects of SGLT2i is reduction of serum UA in patients with type 2 diabetes mellitus (DM) whose estimated glomerular filtration rate (eGFR) was maintained at > 60 ml/min/1.73 m 2 14 – 17 ; however, the effect of lowering serum UA levels by SGLT2i in patients with CKD whose renal function reduced to ˂60 ml/min/1.73 m 2 is unclear.…”

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

“…By increasing glucose concentration in the proximal tubule, where it competes with uric acid for the transporter GLUT9b, SGLT2is reduce reabsorption and promote uric acid urine excretion [ 26 , 41 , 42 ], probably contributing to reduce renal, cardiovascular and mortality risk [ 43 , 44 , 45 ]…”

“…By increasing glucose concentration in the proximal tubule, where it competes with uric acid for the transporter GLUT9b, SGLT2is reduce reabsorption and promote uric acid urine excretion [26,41,42], probably contributing to reduce renal, cardiovascular and mortality risk [43][44][45] In addition, it was suggested that SGLT2is may indirectly inhibit URAT1 through several mechanisms [46,47], including reduction in insulin secretion due to improvement in glucose metabolism [48]. However, serum UA changes induced by SGLT2is may be masked in CKD patients as glycosuria becomes smaller along with GFR reduction.…”

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

“…Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce glucosuria. Ohashi et al [14] reported that their administration enhanced the fractional excretion of glucose from 1.46 to 27.81% in 24 type-2 diabetic patients. Accordingly, the glucosuria observed in this study is comparable to that induced by the administration of SGLT2 inhibitors.…”