PRKAA1 and Other metabolic disease: To add, it is well documented that the inhibition of testicular AMPK is an important contributor to the impairment of spermatogenesis and steroidogenesis, so there is reason to believe that in the patients with T2DM or other metabolic disorders, metformin’s restorative role in male reproductive dysfunction is mainly through normalizing of AMPK in testes [86–89].