A new systematic review and network meta-analysis published in BMJ Open Diabetes Research & Care evaluated the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on serum uric acid levels in patients with chronic kidney disease (CKD). Elevated uric acid is a common complication in CKD, linked to cardiovascular disease and higher mortality risk.

The study included 8 randomized controlled trials (22 arms, 9,367 participants) testing six SGLT-2 inhibitors: dapagliflozin, empagliflozin, sotagliflozin, ipragliflozin, tofogliflozin, and canagliflozin. Trial durations ranged from 12 to 206 weeks.

Pairwise meta-analysis showed that SGLT-2 inhibitors significantly reduced serum uric acid compared with placebo (standardized mean difference [SMD] –0.22; 95% CI –0.42 to –0.03). Subgroup analysis indicated dapagliflozin, empagliflozin, and tofogliflozin had significant effects, with dapagliflozin 10 mg ranked as the most effective uric acid–lowering agent (29.3% probability).

The benefits of SGLT-2 inhibitors were more pronounced in early CKD (stages 1–2) but diminished in advanced CKD (stages 3–4). This indicates reduced renal excretion capacity. No significant increase in adverse events were observed compared to placebo, supporting the overall safety of SGLT-2 inhibitors in this population. SGLT-2 inhibitors are thought to enhance uric acid excretion by inhibiting renal urate transporters such as GLUT9 and URAT1.

It was concluded that SGLT-2 inhibitors, particularly dapagliflozin 10 mg, represent a promising therapeutic option for CKD patients with elevated uric acid. However, there is a need for larger trials to confirm optimal dosing, duration, and patient subgroups that benefit most.