The kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes may be due in part to increased urinary uric acid excretion, a new study suggests.
SGLT2 inhibitors decrease serum uric acid by accentuating urinary uric acid excretion, which is linked to urinary excretion of both glucose and sodium, Danii L.S. Suijk, MD, of Amsterdam University Medical Centers in The Netherlands, and colleagues explained in the Clinical Journal of the American Society of Nephrology. The investigators believe that 2 tubular transporters may play a role in uric acid reabsorption in the nephron: urate transporter 1 (URAT1) and the glucose transporter 9 (GLUT9).
Dr Suijk’s team studied the effects of SGLT2 inhibition using data from 2 randomized clinical trials. In the Renoprotective Effects of Dapagliflozin in Type 2 Diabetes study, serum uric acid significantly decreased by 0.2 mg/dL and 0.4 mg/dL when acute hyperinsulinemia and hyperglycemia states were induced, respectively, compared with a fasted state (5.3 mg/dL). Fractional uric acid excretion significantly increased by 3.2% and 8.9%, respectively. Dapagliflozin treatment likewise significantly reduced plasma uric acid by 0.8 mg/dL during fasting, 1.0 mg/dL during hyperinsulinemia, and 0.8 mg/dL during hyperglycemia. Fractional uric acid excretion significantly increased by 3.0% and 2.6%, respectively, with treatment. “Fractional uric acid excretion strongly correlated to fractional glucose excretion,” the investigators explained.
In the Uric Acid Excretion study, the SGLT2 inhibitor empagliflozin and the URAT blocker benzbromarone both significantly reduced plasma uric acid and increased fractional uric acid excretion. Combining the 2 therapies, however, did not increase uric acid excretion beyond that of benzbromarone monotherapy.
The investigators concluded that in patients with type 2 diabetes and preserved kidney function, SGLT2 inhibition has a uricosuric effect linked to urinary glucose excretion but the effect is blunted by concomitant use of a URAT1 regulator such as benzbromarone.
Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.
Suijk DLS, van Baar MJB, van Bommel EJM, et al. SGLT2 inhibition and uric acid excretion in patients with type 2 diabetes and normal kidney function. Clin J Am Soc Nephrol. Published online March 23, 2022. 17(5):663-671. doi:10.2215/CJN.11480821