Effect of Metformin, Glibenclamide, Sitagliptin and their Combinations on Male Rats Fertility

Background: Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia due to impaired insulin secretion or insulin resistance. It has been increasing at a high rate in the last decades, affecting males and females at reproductive age. Therefore, the current study aimed to assess the safety of some oral hypoglycemic drugs and their combinations on normal male rats’ fertility. Methods: Ninety-six male rats were included in this experiment, and it consisted of two phases. The subchronic phase for 30 days and the chronic phase for 90 days. Each phase contained 48 rats, which were divided into 8 groups (n=6) including the control group and the test groups (metformin 500 mg/kg, glibenclamide 5 mg/kg, sitagliptin 50 mg/kg, metformin 500 mg/kg plus glibenclamide 5 mg/kg, metformin 500 mg/kg plus sitagliptin 50 mg/kg, glibenclamide 5 mg/kg plus sitagliptin 50 mg/kg and the last group was a combination of the three mentioned drugs). The drugs were administered orally. After the completion of the experiment period for both phases, hormonal analysis and sperm parameters were measured. Results: The results of the subchronic and chronic phases revealed that metformin and sitagliptin and their combination affected hormonal and sperm parameters negatively as they reduced testosterone level, sperm count and sperm motility. In comparison, glibenclamide didn’t show any significant effect. Conclusion: This study concludes that metformin exhibits testicular dysfunction. The results of the combination of metformin and glibenclamide in chronic use are encouraging because glibenclamide reduced the testicular dysfunction effect of metformin. Key words: Diabetes mellitus, Glibenclamide, Male fertility, Metformin, Sitagliptin, Oral hypoglycemic agents.