Abstract:

Objective To evaluate the risk of urinary tract infection in patients with type 2 diabetes mellitus (T2DM) treated with five sodium-glucose cotransporter 2 (SGLT2) inhibitors using a network meta-analysis. Methods Chinese and English databases were searched for randomized controlled trials (RCTs) reporting urinary tract infection in patients with T2DM treated with empagliflozin, dapagliflozin, canagliflozin, henagliflozin, and ertugliflozin. The search period extended from database inception to February 28, 2026. After literature screening and data extraction, study quality was assessed using the Cochrane Handbook. Network meta-analysis was performed using RevMan 5.3 and Stata 15.1. Results A total of 20 RCTs involving 19 intervention regimens were included. The network meta-analysis showed that 15 mg ertugliflozin was associated with a lower risk of urinary tract infection than placebo; the risk of urinary tract infection with 15 mg ertugliflozin was also lower than that with 100 mg canagliflozin, 5 mg dapagliflozin, 10 mg empagliflozin, 10 mg dapagliflozin, and 300 mg canagliflozin. The risk of urinary tract infection with 5 mg ertugliflozin was lower than that with 300 mg canagliflozin. No significant differences were found among the other interventions. The ranking results indicated that the risk of urinary tract infection, from low to high, was as follows: 25 mg ertugliflozin <15 mg ertugliflozin <5 mg henagliflozin <10 mg henagliflozin <5 mg ertugliflozin <1 mg ertugliflozin <1 mg empagliflozin <1 mg dapagliflozin < placebo <2.5 mg dapagliflozin <25 mg empagliflozin <50 mg empagliflozin <5 mg empagliflozin <100 mg canagliflozin <5 mg dapagliflozin <10 mg empagliflozin <10 mg ertugliflozin <10 mg dapagliflozin <300 mg canagliflozin. Publication bias analysis suggested a low likelihood of publication bias in this study. Conclusion In terms of reducing the clinical incidence of urinary tract infection, 25 mg ertugliflozin, 15 mg ertugliflozin, and 5 mg henagliflozin demonstrated relatively higher safety.

Key words: diabetes mellitus, type 2, sodium-glucose cotransporter 2 inhibitor, network meta-analysis, urinary tract infection