Antidiabetic pharmacotherapy aiding in fertility restoration: an integrative review of current evidence

Infertility is a growing concern, with metabolic disorders such as type 2 diabetes mellitus (T2DM), obesity and polycystic ovarian syndrome (PCOS) being associated with it. Insulin resistance is seen to be the central feature of these conditions which ends up disrupting hormonal balance and also impairs fertility in both men and women. Hence, understanding the connection between new antidiabetic drugs and fertility can open new possibilities for fertility care. This review studies the role of antidiabetic drugs in improving reproductive outcomes by targeting insulin resistance and related metabolic dysfunctions. Metformin which is the most widely used insulin sensitizer has evidence to improve ovulation in women with PCOS and is seen to be enhancing sperm count, motility and hormone levels in diabetic males by reducing oxidative stress and inflammation. GLP-1 (Glucagon-like peptide-1) receptor agonists include liraglutide and exenatide which support weight loss, improve insulin sensitivity and show positive effects on testosterone levels, ovulation and menstrual regularity. Current growing agents like SGLT2 (Sodium-glucose cotransporter-2) inhibitors and DPP-4 (Dipeptidyl Peptidase-4 inhibitors) inhibitors are also being studied for their potential reproductive too. During pregnancy, glycemic control is critical where metformin and insulin are relatively well-studied, newer agents show variable placental transfer and safety profiles. Further research is required to create new treatment protocols and guidelines to fully understand their long-term reproductive effects in both sexes. Antidiabetic drugs that improve insulin sensitivity offer promising avenues for addressing infertility associated with metabolic disorders. However, gaps remain regarding their long-term preconceptional and postconceptional reproductive effects, underscoring the need for further targeted research.