Effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on serum uric acid levels in patients with chronic kidney disease: a systematic review and network meta-analysis

Elevated serum uric acid levels are an independent predictor of occurrence and development of chronic kidney disease (CKD) and are strongly associated with prognosis. Several clinical trials have demonstrated the benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. To evaluate and rank the effects and safety of various SGLT-2 for serum uric acid levels in patients with CKD. We performed a systematic PubMed, Embase, Scopus, and Web of Science search, including studies published before July 1, 2023. Two researchers independently extracted data on study characteristics and outcomes and assessed study quality using the Cochrane Collaboration's risk of bias tool 2. The gemtc package of R software was used to perform network meta-analysis within a Bayesian framework. The primary outcome was serum uric acid levels, and the secondary outcome was adverse events. Effect sizes are reported as standardized mean differences (SMDs), risk ratio (RR), and 95% CI, respectively. The certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Eight RCTs (9367 participants) were included in this meta-analysis. The results of the paired meta-analysis showed that SGLT-2 inhibitors significantly reduced serum uric acid levels in patients with CKD compared with the placebo group (SMD -0.22; 95% CI -0.42 to -0.03; GRADE: low). Pooled analysis of any adverse events reported in the included studies showed similar incidence rates in the SGLT-2 inhibitor and placebo groups (RR: 0.99; 95% CI 0.97 to 1.00; p=0.147; GRADE: high). Subgroup analysis showed a statistically significant difference only for tofogliflozin. Further network meta-analysis showed that dapagliflozin 10 mg and ipragliflozin 50 mg may be the most effective in reducing uric acid levels. SGLT-2 inhibitors significantly reduced serum uric acid levels in patients with CKD, and dapagliflozin 10 mg and ipragliflozin 50 mg may be the optimal dosages. SGLT-2 inhibitors hold great promise as an antidiabetic therapeutic option for patients with CKD who have elevated serum uric acid levels. PROSPERO registration number: CRD42023456581.