Effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on serum urate levels in patients with and without diabetes: a systematic review and meta-regression of 43 randomized controlled trials

钠-葡萄糖协同转运蛋白2 (SGLT2) 抑制剂对糖尿病患者和非糖尿病患者血清尿酸水平的影响:一项包含43项随机对照试验的系统评价和荟萃回归分析

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Abstract

OBJECTIVES: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce serum urate in patients with type 2 diabetes mellitus. To evaluate if this effect applies to both patients with and without diabetes, we conducted a systematic review and meta-analysis of SGLT2 inhibitors on serum urate levels in this population. METHODS: Four electronic databases (PubMed, Embase, Cochrane and SCOPUS) were searched on 25 September 2021 for articles published from 1 January 2000 up to 25 September 2021, for studies that examined the effect of SGLT2 inhibitors on serum urate in study subjects. Random-effects meta-analysis was performed, with subgroup analyses on the type of SGLT2 inhibitor agent administered, presence of type 2 diabetes mellitus, presence of chronic kidney disease and drug dose. RESULTS: A total of 43 randomized controlled trials, with a combined cohort of 31,921 patients, were included. Both patients with [-31.48 μmol/L; 95% confidence interval (CI): -37.35 to -25.60] and without diabetes (-91.38 μmol/L; 95% CI: -126.53 to -56.24) on SGLT2 inhibitors had significantly lower urate levels when compared with placebo. This treatment effect was similarly observed across different types of SGLT2 inhibitors. However, in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease, the reduction in serum urate with SGLT2 inhibitors became insignificant (95% CI: -22.17 to 5.94, p < 0.01). CONCLUSION: This study demonstrated that SGLT2 inhibitors are beneficial in reducing serum urate in patients with and without diabetes. SGLT2 inhibitors could therefore contribute to the general treatment of hyperuricaemia.

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