Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes

Abstract

Purpose: To investigate the effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on inflammatory cytokines of urogenital tissue in a rat model of type 2 diabetes (T2DM) to infer pharmaceutical influence of dapagliflozin on genitourinary infection or inflammation.Methods: Study animals were divided into the following 4 groups of 10 animals each: (1) the Otsuka Long-Evans Tokushima Fatty (OLETF)-DA group treated with dapagliflozin at 1.0 mg/kg/day, (2) the OLETF-VO group treated with voglibose at 0.6 mg/kg/day, (3) the control group (OLETF-CO) given water, and (4) the Long-Evans Tokushima Otsuka (LETO) rats were included as nondiabetic control group. Changes in blood glucose, 24-hour urine volume, and urine glucose were measured. The interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels in the bladder and the urethra were quantified, respectively.Results: The urine glucose level and the 24-hour urine volume at 12 weeks of treatment were significantly higher in the OLETF-DA group than that in any other group (P<0.05). The cytokine analysis of the bladder and urethra showed higher IL18 and IL-1β in the OLETF-DA and the OLETF-CO groups than that in the OLETF-VO and LETO groups (P<0.05). The cytokine levels did not differ between the OLETF-DA and the OLETF-CO groups, and the level of IL-18 in the OLETF-DA group was higher in the urethra than in the bladder.Conclusions: This study revealed that dapagliflozin increased the urine glucose concentration, resulting in an inflammatory response remain in the urogenital tract as the untreated diabetic rats. Therefore, when treating patients with T2DM with dapagliflozin, careful attention should be paid to genitourinary infection or inflammation.