Effects of sodium-glucose cotransporter-2 inhibitors on serum urate levels and gout in patients with and without type 2 diabetes: a systematic review and network meta-analysis.

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors can decrease serum uric acid (sUA) levels and have potential in the management of glucose levels and cardiorenal protection in patients.

Aim: This systematic review and network meta-analysis aimed to investigate the effects of SGLT-2 inhibitors on sUA levels and incidence of gout in patients with or without type 2 diabetes.

Method: A systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and Clinical Trials databases was performed to retrieve relevant articles published from inception to April 27, 2025, focusing on the impact of SGLT-2 inhibitors on sUA levels or the incidence of gout in the study participants. We performed a Bayesian random-effects network meta-analysis of the included studies using the Markov Chain Monte Carlo simulation techniques. The grading of recommendations, assessment, development, and evaluation approach was used to assess the certainty of the evidence.

Results: A total of 57 trials were included. All SGLT-2 inhibitors reduced sUA levels. These inhibitors demonstrated a spectrum of sUA-lowering effects, with empagliflozin and dapagliflozin exhibiting particularly robust efficacy. Specifically, empagliflozin (10 mg: - 43 [95% CI - 52.45 to - 33.66]; 25 mg: - 41.99 [95% CI - 51.93 to - 31.9]; 50 mg: - 35.77 [95% CI - 68.04 to - 3.53]) and dapagliflozin (5 mg: - 36.91 [95% CI - 49.5 to - 24.46]; 10 mg: - 34.98 [95% CI - 43.75 to - 26.44]) displayed superior reductions in sUA levels compared to other agents within the class. Although there was a potential reduction in the incidence of gout associated with SGLT-2 inhibitors, the difference was not statistically significant.

Conclusion: Future long-term studies should consider SGLT-2 inhibitors for individuals requiring sUA reduction and gout management. These results could serve as a reference for future guidelines addressing the treatment of individuals with diabetes, necessitating sUA lowering and gout management. Trial Registration PROSPERO registration number CRD42024521695.