Background: Sitagliptin is a dipeptidyl peptidase-4 inhibitor indicated for the treatment of type 2 diabetes mellitus. Despite its therapeutic benefits, it induces oxidative stress and causes reproductive toxicity. Therefore, this study investigated the po- tential antioxidant effects of myo-inositol on sperm parameters in diabetic mice treated with sitagliptin. Materials and Methods: In this study, twenty-four adult NMRI male mice were randomly divided into five groups: control, dia- betic (streptozotocin [150 mg/kg] + nicotinamide [110 mg/kg]), diabetic + sitagliptin (30 mg/kg/bw), diabetic + myo-inositol (300 mg/kg/bw), and diabetic + sitagliptin + myo-inositol and they were treated for a period of 35 days. After dissecting the mice, the caudal epididymis was isolated in Ham's F10 culture medium, and the extracted sperm were analyzed for various sperm parameters. Data were statistically analyzed by spss soft- ware, One-Way ANOVA and Tukey's test, and the means differ- ence was considered significant at the P<0.05. Results: The diabetic group showed a significant reduction in the mean number, viability, motility, morphology and mem- brane integrity of the sperm cells when compared to the control group (P<0.05). These parameters significantly decreased in the diabetic + sitagliptin group compared to the control group (P<0.05) and didn't show a significant difference compared to the diabetic group (p>0.05). These side effects were compen- sated for in the diabetic + sitagliptin + myo-inositol group com- pared to the diabetic + sitagliptin group. Conclusion: Our results revealed that sitagliptin treatment sig- nificantly impairs sperm quality in diabetic mice. Simultaneous treatment of sitagliptin and myo-inositol effectively mitigates these adverse effects.
