SGLT‐2 inhibitors enhance the effect of metformin to ameliorate hormonal changes and inflammatory markers in a rat PCOS model

Polycystic ovary syndrome (PCOS) is a common endocrine, reproductive, and metabolic disorder affecting females. The management of PCOS is challenging and current interventions are not enough to deal with all consequences of this syndrome. We explored the beneficial effect of combined sodium glucose co transporter‐2 inhibitor (SGLT‐2i); (empagliflozin) and metformin on hormonal and metabolic parameters in an animal model of PCOS and insulin resistance (IR). Forty adult female Wistar rats divided into five groups: control, PCOS‐IR, PCOS‐IR treated with metformin, PCOS‐IR treated with empagliflozin, and PCOS‐IR treated with combined metformin and empagliflozin. Single modality treatment with metformin or empagliflozin yielded significant improvement in body mass index, insulin resistance, lipid profile, sex hormones, inflammatory markers, and ovarian cystic follicles. Combined metformin with empagliflozin expressed further significant improvement in sex hormones, inflammatory markers with disappearance of ovarian cystic follicles. The superior significant improvement with combined treatment over the single modality was in line with significant improvement in the ovarian AMPKα‐SIRT1 expression.