Risk of urinary tract infection in patients with type 2 diabetes treated with dapagliflozin: A systematic review and meta-analysis of randomized controlled studies

Abstract

Abstract As a selective inhibitor of sodium-glucose cotransporter 2, dapagliflozin is widely used in the treatment of type 2 diabetes mellitus (T2DM). However, whether it increases the risk of urinary tract infection (UTI) remains an ongoing issue. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to estimate the short-term and long-term risks of UTI in patients with T2DM who received dapagliflozin at different doses. As a selective inhibitor of sodium-glucose cotransporter 2, dapagliflozin is widely used in the treatment of type 2 diabetes mellitus (T2DM). However, whether it increases the risk of urinary tract infection (UTI) remains an ongoing issue. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to estimate the short-term and long-term risks of UTI in patients with T2DM who received dapagliflozin at different doses. We searched the PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov website from each database's inception to December 2021. The review protocol was previously registered in the PROSPERO database (CRD42022299899). A total of 40 RCTs involving 35573 patients were assessed for eligibility. The results showed that dapagliflozin imposed a higher risk of UTI compared to placebo and other active treatments, with a heterogeneity of 11% (OR 1.17, 95% CI 1.04-1.31, P=0.006). In the subgroup analysis, dapagliflozin 10 mg/d with a treatment period >24 weeks was associated with a significantly higher UTI risk than placebo or other active treatments (OR 1.27, 95% CI 1.13-1.43, P＜0.0001). The ORs for dapagliflozin as monotherapy and combination therapy in the control group were 1.05 (95% CI 0.88-1.25, P=0.571) and 1.27 (95% CI 1.09-1.48, P=0.008), respectively. Overall, dapagliflozin 10 mg daily with a treatment duration of more than 24 weeks may significantly increase the risk of UTI in patients with T2DM. The combination of dapagliflozin and other glucose-lowering drugs might be associated with a higher risk of UTI. Therefore, high-dose, long-term treatment and add-on therapy of dapagliflozin call for careful consideration of the risk of UTI in T2DM patients.