Effects of empagliflozin on serum uric acid level of patients with type 2 diabetes mellitus: a systematic review and meta‐analysis

Background Serum uric acid levels are higher in patients with type 2 diabetes and prediabetes compared to healthy individuals, and hyperuricemia causes a significant rate of complications and mortality through heart and kidney diseases. Accordingly, the present systematic review and meta-analysis aimed to investigate the effect of empagliflozin on serum uric acid levels. Materials and methods Electronic databases, including PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were used to search papers until May 22, 2023. Data analysis was conducted by STATA Version 14, and P-value < 0.05 were considered statistically significant. Results The results obtained from the combination of 12 studies with 7801 samples of diabetic patients indicated that in the empagliflozin group, the serum uric acid levels of the patients decreased ([standardized mean difference (SMD): - 1.97 (95%CI - 3.39, - 0.55)], Systolic blood pressure (SBP) [SMD: - 2.62 (95%CI - 3.87, - 1.37)] and diastolic blood pressure (DBP) [SMD: - 0.49 (95%CI - 0.68, - 0.29)]). On the other side, empagliflozin treatment did not affect the patients' HbA1c levels ([SMD: - 2.85 (95%CI - 6.14, 0.45)], eGFR [SMD: 0.78 (95%CI - 0.63, 2.18)], creatinine [SMD:0.11 (95%CI - 0.10, 0.31)], LDL [SMD: 0.14 (95%CI - 0.43, 0.71)], and HDL [SMD:1.38 (95%CI - 0.22, 2.99)]). Compared with the placebo, empagliflozin was more effective in reducing the uric acid levels ([SMD: - 1.34 (95%CI - 2.05, - 0.63)], SBP [SMD: - 2.11 (95%CI - 3.89, - 0.33)], and HbA1c [SMD: - 1.04 (95%CI - 1.95, - 0.13)]). Moreover, compared with sitagliptin also, empagliflozin was more effective in reducing uric acid levels ([SMD: - 1 (95%CI - 1.78, - 0.22)], and creatinine [SMD: - 1.60 (95%CI - 2.28, - 0.92)]) and increasing eGFR levels [SMD: 0.99 (95%CI: 0.37, 1.62)] of the patients. Compared with dapagliflozin also, empagliflozin caused a reduction in eGFR level [SMD: - 0.45 (95%CI - 0.82, - 0.08)]. Conclusion Empagliflozin treatment was effective in controlling diabetic patients' hyperuricemia and hypertension. Keywords: Uric acid, Urate, Monosodium urate, Empagliflozin, Sodium-glucose transporter 2 inhibitors, SGLT-2 inhibitors, Gliflozins