1379-P: The Positive Effects of Dapagliflozin on the Functioning and Histological Changes in the Type 2 Diabetic Bladder

Introduction and Objective: Dapagliflozin (DAPA) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that promotes renal glucose excretion and serves as a therapeutic intervention for controlling blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Diabetic bladder dysfunction (DBD) caused by autonomic neuropathy and structural remodeling is common in patients with DM. This study aimed to assess the effects of DAPA on bladder function in a rat model of DM. Methods: Male Wistar rats (n=32) were divided into 4 groups: control, control + DAPA, streptozotocin-induced DM, and DM + DAPA. A high-fat diet was given to the DM groups. Therapy groups were given DAPA therapy (1 mg/kg, oral) for 4 weeks following DM induction. The bladder strips were used to measure the contractile responses in vitro. Using Western blotting and immunohistochemistry, SGLT1, SGLT2, NF-κB, TNF-a and IL-10 protein expression was examined. The ratio of smooth muscle to collagen was determined by Masson’s trichrome staining. Results: In diabetic rats, blood glucose levels increased and contractile responses to electrical field stimulation, carbachol, KCl and adenosine triphosphate in the detrusor smooth muscle decreased; these responses partially returned to normal following therapy. The increase in the expression of SGLT1, SGLT2, NF-κB, TNF-a, IL-10 and the ratio of collagen to smooth muscle in diabetic rats were restored by DAPA therapy. Conclusion: DAPA's benefits in DBD extend beyond glycemic control, offering a novel therapeutic avenue for this debilitating complication. Inflammatory and fibrotic markers modulation, alongside improved contractility, highlights its potential to address multiple facets of DBD pathology. This positions SGLT2 inhibitors as a promising strategy for improving bladder function in T2DM patients, potentially mitigating the need for more invasive treatments. Furthermore, it can be crucial to explore the efficacy of DAPA in combination with other therapeutic agents for DBD and to conduct clinical trials in patients with DBD. Disclosure F. Korkmaz: None. D. Yilmaz Oral: None. U. Mendes: None. S. Gur: None.