Dapagliflozin and metformin combination therapy modulates lipid metabolism and oxidative stress in a sex-dependent manner
Purpose: To investigate the effect of dapagliflozin combined with metformin on metabolic, oxidative and endothelial factors, with a particular focus on sex-specific variation.Methods: A total of 32 patients (18 males, 14 females) were recruited from Al-Salam Teaching Hospital in Mosul city, Iraq. The patients received metformin monotherapy (1000 mg/day) from October 2024 to April 2025. Thereafter, dapagliflozin (10 mg/day) was administered as an adjuvant therapy for 8 weeks. Serum samples were collected before and 8 weeks after dapagliflozin therapy, and HbA1c, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), malondialdehyde (MDA), total antioxidant status (TAS), vascular and intercellular cell adhesion molecule 1 (VCAM-1 and ICAM-1) were measured using enzyme-linked immunosorbent assay (ELISA).Results: Dapagliflozin therapy significantly reduced glycated haemoglobin (HbA1c), cholesterol, LDL, and atherogenic index, with a significant reduction of TG in males compared to females (p < 0.05). Serum MDA was significantly reduced in both sexes (p < 0.01), while TAS was significantly higher in females compared to males (p < 0.001). Furthermore, VCAM-1 and ICAM-1 did not significantly change in either sex.Conclusion: Treatment with dapagliflozin following metformin therapy induced favourable hypolipidemic and oxidative benefits with sex-related differences, which highlighted the importance of considering biological sex when evaluating antidiabetic agents.