Hani M Almukhtar1 
,
Adil M Najm2,
Shamil H Othman3
For correspondence:- Hani Almukhtar Email: hanialmukhtar@uomosul.edu.iq Tel:00964-7743531650
Received: 9 April 2026 Accepted: 15 July 2026 Published: 31 July 2026
Citation: Almukhtar HM, Najm AM, Othman SH. Dapagliflozin and metformin combination therapy modulates lipid metabolism and oxidative stress in a sex dependent manner. Trop J Pharm Res 2026; 25(7):947-953 doi: https://dx.doi.org/10.4314/tjpr.v25i7.6
© 2026 The authors.
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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
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