Background and objective: To investigate whether dapagliflozin (as a selective inhibitor of sodium-glucose cotransporter 2), increases the risk of urinary tract infection (UTI) in the treatment of type 2 diabetes mellitus (T2DM) remains an ongoing issue. 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.
Methods: The PubMed, EMBASE, and the Cochrane Library and ClinicalTrials.gov website were searched up to December 31, 2022. Only RCTs involving adult T2DM patients with a trial duration of at least 12 weeks were included. The data were summarized using random- or fixed-effects models based on overall heterogeneity. A subgroup analysis was also performed. The review protocol was previously registered in the PROSPERO database (CRD42022299899).
Results: In total, 42 RCTs involving 35,938 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% (odds ratio [OR] 1.17, 95% CI 1.04-1.31, p = 0.006). In the subgroup analysis, dapagliflozin 10 mg/day with a treatment period of > 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.
Conclusions: High-dose, long-term treatment, and add-on therapy of dapagliflozin call for careful consideration of the risk of UTI in T2DM patients.
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.