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Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats
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1708775 Vol 8 · Issue 11 Download Paper

Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats

Eboagwu Lynda Ijeoma Monago-Ighorodje Comfort

Subject area: Science,Engineering and Technology  ·  Area of research: Management of Type 2 Diabetes Mellitus

Abstract

Metformin and empagliflozin are well-established antidiabetic agents with proven efficacy in glycemic control. This study evaluated and compared their effects on hematological parameters in high-fat diet-streptozotocin (HFD-STZ)-induced diabetic rats over 9 weeks. Both drugs exhibited immunomodulatory, anti-inflammatory, and hematoprotective properties, as evidenced by significant reductions in white blood cell counts, particularly in the low-dose empagliflozin group, indicating early and sustained suppression of diabetes-associated chronic inflammation. Despite these benefits, hemoglobin levels remained significantly reduced across all treatment groups, suggesting persistent anemia likely linked to oxidative stress and impaired erythropoiesis. Notably, red blood cell counts and hematocrit values increased in the high-dose empagliflozin and metformin-treated groups, indicating partial recovery of erythropoiesis. Mean corpuscular volume remained stable, implying preserved red blood cell maturation and suggesting anemia arose primarily from decreased hemoglobin content rather than changes in cell size. Platelet counts consistently declined under treatment, reflecting potential anti-inflammatory effects while also raising concerns about thrombocytopenia and bleeding risk in diabetic conditions. These findings highlight the multifaceted roles of metformin and empagliflozin beyond glycemic control, underscoring their impact on hematological health and inflammation in diabetes.

Keywords

Metformin, Empagliflozin, Erythropoiesis, Antidiabetic Agents.

References

[1] American Diabetes Association Professional Practice Committee, & American Diabetes Association Professional Practice Committee: (2022). 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2022. Diabetes care, 45(Supplement_1), S17-S38.

[2] Andersen, C., Omar, M., Glenthoej, A., Fassi, D. E., Moeller, H. J., Styrishave, B., ... & Jensen, J. (2022). Direct effects of empagliflozin on erythropoiesis in heart failure: data from the Empire HF trial. European Heart Journal, 43(Supplement_2), ehac544-968.

[3] Arefin, A., & Gage, M. C. (2023). Metformin, empagliflozin, and their combination modulate ex-vivo macrophage inflammatory gene expression. International Journal of Molecular Sciences, 24(5), 4785.

[4] Backe, M. B., Moen, I. W., Ellervik, C., Hansen, J. B., & Mandrup-Poulsen, T. (2016). Iron regulation of pancreatic beta-cell functions and oxidative stress. Annual Review of Nutrition, 36(1), 241-273.

[5] Bissinger, R., Bhuyan, A. A. M., Qadri, S. M., & Lang, F. (2019). Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases. The FEBS journal, 286(5), 826-854.

[6] Bolscher, M., Koster, S. C., Koopmans, M., Haitsma Mulier, J. L., Derde, L. P., & Juffermans, N. P. (2024). Anti-inflammatory therapies are associated with delayed onset of anemia and reduction in transfusion requirements in critically ill patients: results from two studies. Critical Care, 28(1), 114.

[7] Brito, A. K. D. S., Mendes, A. V. D. S., Timah Acha, B., Santos Oliveira, A. S. D. S., Lopes Macedo, J., Suzuki Cruzio, A., ... & Arcanjo, D. D. R. (2025). Experimental Models of Type 2 Diabetes Mellitus Induced by Combining Hyperlipidemic Diet (HFD) and Streptozotocin Administration in Rats: An Integrative Review. Biomedicines, 13(5), 1158.

[8] Budzianowski, J., Rzezniczak, J., Hiczkiewicz, J., Kasprzak, D., Winnicka-ZieliDska, A., Musielak, B., ... & Burchardt, P. (2021). Beneficial effects of empagliflozin on hematocrit levels in a patient with severe anemia. DARU

[9] Cardoso, C. R., Leite, N. C., & Salles, G. F. (2021). Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study. Cardiovascular Diabetology, 20, 1-13.

[10] Ebrahim, H., Fiseha, T., Ebrahim, Y., & Bisetegn, H. (2022). Comparison of hematological parameters between type 2 diabetes mellitus patients and healthy controls at Dessie comprehensive specialized hospital, Northeast Ethiopia: Comparative cross-sectional study. PLoS One, 17(7), e0272145.

[11] Hadjadj, S., Rosenstock, J., Meinicke, T., Woerle, H. J., & Broedl, U. C. (2016). Initial combination of empagliflozin and metformin in patients with type 2 diabetes. Diabetes Care, 39(10), 1718-1728.

[12] Han, X., Tao, Y. L., Deng, Y. P., Yu, J. W., Cai, J., Ren, G. F., ... & Jiang, G. J. (2017). Metformin ameliorates insulitis in STZ-induced diabetic mice. PeerJ, 5, e3155.

[13] Harrison, A. V., Lorenzo, F. R., & McClain, D. A. (2023). Iron and the pathophysiology of diabetes. Annual review of physiology, 85(1), 339-362.

[14] Iannantuoni, F., M. de Marañon, A., Diaz-Morales, N., Falcon, R., Bañuls, C., Abad-Jimenez, Z., ... & Rovira-Llopis, S. (2019). The SGLT2 inhibitor empagliflozin ameliorates the inflammatory profile in type 2 diabetic patients and promotes an antioxidant response in leukocytes. Journal of clinical medicine, 8(11), 1814.

[15] International Diabetes Federation 2025. https://diabetesatlas.org. Assessed on 23rd May,2025.

[16] Jani, M., Cankar, M., `mid, J., France `tiglic, A., Jerin, A., `abovi

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How to cite this paper

Eboagwu Lynda Ijeoma, Monago-Ighorodje Comfort "Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats" Iconic Research And Engineering Journals Volume 8 Issue 11 2025 Page 2130-2137
Eboagwu Lynda Ijeoma, Monago-Ighorodje Comfort "Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats" Iconic Research And Engineering Journals, vol. 8, no. 11, May. 2025
Eboagwu Lynda Ijeoma, Monago-Ighorodje Comfort (2025). Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats. Iconic Research And Engineering Journals, 8(11).
Eboagwu Lynda Ijeoma, Monago-Ighorodje Comfort "Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats" Iconic Research And Engineering Journals, vol. 8, no. 11, May. 2025.
@article{1708775,
      author = {Eboagwu Lynda Ijeoma, Monago-Ighorodje Comfort},
      title = {Comparative Effects of Metformin and Empagliflozin on Hematological Parameters in STZ-Induced Diabetic Rats},
      journal = {Iconic Research And Engineering Journals},
      year = {2025},
      volume = {8},
      number = {11},
      pages = {2130-2137},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1708775.pdf},
      abstract = {Metformin and empagliflozin are well-established antidiabetic agents with proven efficacy in glycemic control. This study evaluated and compared their effects on hematological parameters in high-fat diet-streptozotocin (HFD-STZ)-induced diabetic rats over 9 weeks. Both drugs exhibited immunomodulatory, anti-inflammatory, and hematoprotective properties, as evidenced by significant reductions in white blood cell counts, particularly in the low-dose empagliflozin group, indicating early and sustained suppression of diabetes-associated chronic inflammation. Despite these benefits, hemoglobin levels remained significantly reduced across all treatment groups, suggesting persistent anemia likely linked to oxidative stress and impaired erythropoiesis. Notably, red blood cell counts and hematocrit values increased in the high-dose empagliflozin and metformin-treated groups, indicating partial recovery of erythropoiesis. Mean corpuscular volume remained stable, implying preserved red blood cell maturation and suggesting anemia arose primarily from decreased hemoglobin content rather than changes in cell size. Platelet counts consistently declined under treatment, reflecting potential anti-inflammatory effects while also raising concerns about thrombocytopenia and bleeding risk in diabetic conditions. These findings highlight the multifaceted roles of metformin and empagliflozin beyond glycemic control, underscoring their impact on hematological health and inflammation in diabetes.},
      keywords = {Metformin, Empagliflozin, Erythropoiesis, Antidiabetic Agents.},
      month = {May},
  }