Effects of metformin and glutathione alone and in coformulation with other compounds on reproductive health and fertility in diabetic male rodents: A systematic review

Objective: To systematically review the effects of administering metformin and glutathione alone and in coformulation with other compounds on the fertility and reproductive health of diabetic male rodents. Methods: The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed to conduct this systematic review. Studies published until August 2024 in PubMed, Web of Science, and Scopus databases were searched, identified, screened, and selected for a detailed review. The keywords included metformin, diabetes, reproduction, glutathione, and rodent models. Results: A total of 166 studies were identified, of which 11 met the inclusion criteria and were included in the qualitative synthesis. One additional study was identified through snowballing and citation tracking, bringing the total to 12 studies. The findings indicate that metformin and glutathione, administered alone or in combination with other compounds, improved sperm count, motility, and morphology; restored reproductive hormone levels; reduced oxidative stress markers; and improved testicular histopathology in diabetic male rodents. Conclusions: Coformulation of metformin and glutathione with other compounds was found to be more effective in improving fertility and reproductive parameters in diabetic male rodents compared to mono-administration. However, further studies on the coformulation of metformin and glutathione are needed to confirm their efficacy and elucidate the underlying mechanisms. Study registration: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42024561820.