Evaluation of toxic effects of dapagliflozin on reproductive system in diabetic rats.

Background: Dapagliflozin (DAPA), sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an insulin-independent antidiabetic drug used to control hyperglycaemia by promoting glucose excretion from the kidney. Its adverse effects include orthostatic hypotension, dehydration and urinary tract and genital infections caused by glycosuria. DAPA is subjected to constant additional monitoring, as drugrelated adverse reactions are frequently updated in line with the results of case studies, clinical trials and in vivo studies. Some antidiabetic drugs have shown potential harmful effects on the male reproductive system; however, the effects of DAPA have not been sufficiently studied in this capacity. Aiming to fill this gap in the literature, the present work investigates the toxic effects of DAPA on the male reproductive system.

Methods: Diabetes was induced using streptozotocin (STZ) in adult male Sprague-Dawley (SD) rats. DAPA (10 mg/kg) was administered by gavage to the diabetic rats over 28 days, after which the animals were sacrificed. The biochemical, morphological and histological examinations were performed on testicle, sperm and plasma samples.

Results: As a result of this study, we observed reproductive system damage in the form of induction of apoptosis in the seminiferous tubules, changes in testis and sperm parameters and oxidative damage, alongside the development of diabetes in test animals. With the exception of sperm morphological damage, the changes observed in diabetic animals treated with DAPA were similar to those of the control group. Improvements were observed in histological, hormonal and proliferative parameters in the DAPA group compared to the DC group.

Discussion: Even if DAPA is found to have antioxidant effects, it may raise abnormal sperm counts through a mechanism completely independent of these effects and thus may not have a significant toxic effect on the male reproductive system.