METFORMIN AND ITS EFFECT ON CARDIOVASCULAR OUTCOMES AND MORTALITY IN DIABETES

Main Article Content

Anurag Rawat
Mahwish Tariq
Najibullah Niazman
Romasa Muzaffar Ali Joyo
Payal
Qamar Zaman
Akashnath Kivalur Ganeshanath

Keywords

Metformin, Type 2 Diabetes Mellitus, Mortality, Systematic Review, Meta-Analysis

Abstract

Background: Metformin is a widely prescribed medication for managing type 2 diabetes mellitus (T2DM) and has been a cornerstone in diabetes care for decades. Beyond its glucose-lowering effects, there is increasing interest in its impact on cardiovascular outcomes and mortality.


Objective: This systematic review and meta-analysis aimed to evaluate the effects of metformin on cardiovascular events and all-cause mortality in patients with T2DM.


Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Cochrane Library, Scopus, and Web of Science, to identify studies assessing metformin’s impact on cardiovascular outcomes and mortality. Studies included randomized controlled trials (RCTs) and observational studies with relevant outcome measures. Data were synthesized to estimate pooled relative risks (RR) and hazard ratios (HR) for cardiovascular events and mortality associated with metformin use.


Results: A total of 15 studies with 12,345 participants were included in the analysis. Metformin use was associated with a significant reduction in major cardiovascular events, including myocardial infarction and stroke, with a pooled RR of 0.76 (95% CI: 0.67–0.87). Additionally, metformin was linked to a significant decrease in all-cause mortality, with a pooled HR of 0.81 (95% CI: 0.71–0.93). Subgroup analyses indicated that RCTs showed a stronger association between metformin use and reduced cardiovascular events compared to observational studies. Higher dosages of metformin were also associated with greater reductions in cardiovascular outcomes and mortality. Sensitivity analyses confirmed the robustness of these findings, with exclusion of high-risk studies not significantly altering the results.


Conclusions: Metformin is associated with significant reductions in cardiovascular events and mortality in patients with T2DM. These findings support the continued use of metformin not only for glycemic control but also for its cardiovascular benefits. Further research is needed to confirm these effects and explore underlying mechanisms, as well as to compare metformin with other antidiabetic treatments to optimize patient outcomes.


 


 

Abstract 97 | pdf Downloads 15

References

1. Ahmad, E., Sargeant, J. A., Zaccardi, F., Khunti, K., Webb, D. R., & Davies, M. J. (2020). Where does metformin stand in modern day management of type 2 diabetes? Pharmaceuticals, 13(12), 427.
2. Aktas, G., Atak Tel, B. M., Tel, R., & Balci, B. (2023). Treatment of type 2 diabetes patients with heart conditions. Expert Review of Endocrinology & Metabolism, 18(3), 255-265.
3. Arte, P. A., Tungare, K., Bhori, M., Jobby, R., & Aich, J. (2024). Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach. Human Cell, 37(1), 54-84.
4. Bailey, C. J. (2024). Metformin: Therapeutic profile in the treatment of type 2 diabetes. Diabetes, Obesity and Metabolism, 26, 3-19.
5. Bolde, D. S., Bhanap, S. S., & Chavan, V. V. (2024). Metformin: An overview. World Journal of Biology Pharmacy and Health Sciences, 18(3), 186-198.
6. Cai, X., Zhang, Y., Li, M., Wu, J. H., Mai, L., Li, J., Yang, Y., Hu, Y., & Huang, Y. (2020). Association between prediabetes and risk of all cause mortality and cardiovascular disease: updated meta-analysis. Bmj, 370.
7. Chen, X., Shu, Y., & Lin, X. (2024). Impact of canagliflozin combined with metformin therapy on reducing cardiovascular risk in type 2 diabetes patients. Diabetology & Metabolic Syndrome, 16(1), 199.
8. Dihoum, A., Rena, G., Pearson, E. R., Lang, C. C., & Mordi, I. R. (2023). Metformin: evidence from preclinical and clinical studies for potential novel applications in cardiovascular disease. Expert Opinion on Investigational Drugs, 32(4), 291-299.
9. Geng, Y., Wang, Z., Xu, X., Sun, X., Dong, X., Luo, Y., & Sun, X. (2024). Extensive therapeutic effects, underlying molecular mechanisms and disease treatment prediction of Metformin: a systematic review. Translational Research, 263, 73-92.
10. Ghavimi, H., Sheidaei, S., Vaez, H., Zolali, E., Asgharian, P., & Hamishehkar, H. (2018). Metformin-attenuated sepsis-induced oxidative damages: a novel role for metformin. Iranian journal of basic medical sciences, 21(5), 469.
11. Henning, R. J. (2018). Type-2 diabetes mellitus and cardiovascular disease. Future cardiology, 14(6), 491-509.
12. LaMoia, T. E., & Shulman, G. I. (2021). Cellular and molecular mechanisms of metformin action. Endocrine reviews, 42(1), 77-96.
13. Lv, Z., & Guo, Y. (2020). Metformin and its benefits for various diseases. Frontiers in endocrinology, 11, 191.
14. Ma, C.-X., Ma, X.-N., Guan, C.-H., Li, Y.-D., Mauricio, D., & Fu, S.-B. (2022). Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Cardiovascular diabetology, 21(1), 74.
15. Malaekeh-Nikouei, A., Shokri-Naei, S., Karbasforoushan, S., Bahari, H., Rahimi, V. B., Heidari, R., & Askari, V. R. (2023). Metformin beyond an anti-diabetic agent: A comprehensive and mechanistic review on its effects against natural and chemical toxins. Biomedicine & Pharmacotherapy, 165, 115263.
16. Nasri, H., & Rafieian-Kopaei, M. (2014). Metformin: current knowledge. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences, 19(7), 658.
17. Petrie, J. R. (2024). Metformin beyond type 2 diabetes: Emerging and potential new indications. Diabetes, Obesity and Metabolism, 26, 31-41.
18. Poznyak, A. V., Litvinova, L., Poggio, P., Moschetta, D., Sukhorukov, V. N., & Orekhov, A. N. (2022). From diabetes to atherosclerosis: potential of metformin for management of cardiovascular disease. International journal of molecular sciences, 23(17), 9738.
19. Zareini, B., Blanche, P., D’Souza, M., Elmegaard Malik, M., Nørgaard, C. H., Selmer, C., Gislason, G., Kristensen, S. L., Køber, L., & Torp-Pedersen, C. (2020). Type 2 diabetes mellitus and impact of heart failure on prognosis compared to other cardiovascular diseases: a nationwide study. Circulation: Cardiovascular Quality and Outcomes, 13(7), e006260.

Most read articles by the same author(s)