Metformin - An Antidiabetic Drug With Anti-aging, Cardioprotective And Potential Anti-cancer Properties
DOI:
https://doi.org/10.12775/JEHS.2025.85.66564Keywords
metformin, anti-aging, cardioprotective, anti-cancer, AMPK, diabetes, anti-inflammatory, cancer, mTORAbstract
Introduction: This review aims to examine the role of metformin, a widely used oral antihyperglycemic agent, and its emerging potential cardioprotective, anticancer, and anti-aging effects.
Materials and Methods: A comprehensive review of the literature was conducted using the PubMed and Google Scholar databases using the following keywords: “metformin”, “anti-aging”, “cardioprotective”, ”anti-cancer”, “AMPK”, “diabetes”, “anti-inflammatory”, “cancer”, “mTOR”
Summary: Metformin, originally developed to treat type 2 diabetes, has been widely used due to its effectiveness in lowering blood glucose without causing hypoglycemia, and it exhibits a strong safety profile with additional benefits like weight loss and improved cardiovascular health. Beyond diabetes management, metformin shows promising anti-aging effects by improving mitochondrial function, regulating protein homeostasis, reducing inflammation, and modulating the microbiome. Furthermore, metformin has potential protective roles against dementia, skin aging, cardiovascular diseases, and various cancers through mechanisms involving AMPK activation and immune modulation.
Conclusions: Metformin demonstrates a wide range of beneficial effects beyond glucose control, including anti-aging, anti-inflammatory, cardiovascular protective, and potential anticancer properties. Through its cellular and metabolic mechanisms, metformin shows promise not only as a treatment for type 2 diabetes but also in the prevention and management of various age-related diseases. However, more high-quality clinical studies are needed to confirm these findings.
References
1. Corcoran C, Jacobs TF. Metformin. 2023 Aug 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30085525.
2. Flory J, Lipska K. Metformin in 2019. JAMA. 2019 May 21;321(19):1926-1927. doi: 10.1001/jama.2019.3805. PMID: 31009043; PMCID: PMC7552083.
3. Dutta S, Shah RB, Singhal S, Dutta SB, Bansal S, Sinha S, Haque M. Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes. Drug Des Devel Ther. 2023 Jun 26;17:1907-1932. doi: 10.2147/DDDT.S409373. PMID: 37397787; PMCID: PMC10312383.
4. Gonzalez-Lopez C, Wojeck BS. Role of metformin in the management of type 2 diabetes: recent advances. Pol Arch Intern Med. 2023 Jun 23;133(6):16511. doi: 10.20452/pamw.16511. Epub 2023 Jun 14. PMID: 37317976.
5. Sanchez-Rangel E, Inzucchi SE. Metformin: clinical use in type 2 diabetes. Diabetologia. 2017 Sep;60(9):1586-1593. doi: 10.1007/s00125-017-4336-x. Epub 2017 Aug 2. PMID: 28770321.
6. Drzewoski J, Hanefeld M. The Current and Potential Therapeutic Use of Metformin-The Good Old Drug. Pharmaceuticals (Basel). 2021 Feb 5;14(2):122. doi: 10.3390/ph14020122. PMID: 33562458; PMCID: PMC7915435.
7. Zhang T, Zhou L, Makarczyk MJ, Feng P, Zhang J. The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications. Molecules. 2025 Feb 10;30(4):816. doi: 10.3390/molecules30040816. PMID: 40005128; PMCID: PMC11858480.
8. Mohammed I, Hollenberg MD, Ding H, Triggle CR. A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan. Front Endocrinol (Lausanne). 2021 Aug 5;12:718942. doi: 10.3389/fendo.2021.718942. PMID: 34421827; PMCID: PMC8374068.
9. Hu D, Xie F, Xiao Y, Lu C, Zhong J, Huang D, Chen J, Wei J, Jiang Y, Zhong T. Metformin: A Potential Candidate for Targeting Aging Mechanisms. Aging Dis. 2021 Apr 1;12(2):480-493. doi: 10.14336/AD.2020.0702. PMID: 33815878; PMCID: PMC7990352.
10. Soukas AA, Hao H, Wu L. Metformin as Anti-Aging Therapy: Is It for Everyone? Trends Endocrinol Metab. 2019 Oct;30(10):745-755. doi: 10.1016/j.tem.2019.07.015. Epub 2019 Aug 9. PMID: 31405774; PMCID: PMC6779524.
11. Kulkarni AS, Gubbi S, Barzilai N. Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab. 2020 Jul 7;32(1):15-30. doi: 10.1016/j.cmet.2020.04.001. Epub 2020 Apr 24. PMID: 32333835; PMCID: PMC7347426.
12. Chin-Hsiao T. Metformin and the Risk of Dementia in Type 2 Diabetes Patients. Aging Dis. 2019 Feb 1;10(1):37-48. doi: 10.14336/AD.2017.1202. PMID: 30705766; PMCID: PMC6345339.
13. Gouveri E, Papanas N. Τhe Endless Beauty of Metformin: Does It Also Protect from Skin Aging? A Narrative Review. Adv Ther. 2023 Apr;40(4):1347-1356. doi: 10.1007/s12325-023-02434-z. Epub 2023 Jan 30. PMID: 36715895.
14. Chen Q, Zhang H, Yang Y, Zhang S, Wang J, Zhang D, Yu H. Metformin Attenuates UVA-Induced Skin Photoaging by Suppressing Mitophagy and the PI3K/AKT/mTOR Pathway. Int J Mol Sci. 2022 Jun 23;23(13):6960. doi: 10.3390/ijms23136960. PMID: 35805987; PMCID: PMC9266365.
15. Chen S, Gan D, Lin S, Zhong Y, Chen M, Zou X, Shao Z, Xiao G. Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms. Theranostics. 2022 Mar 6;12(6):2722-2740. doi: 10.7150/thno.71360. PMID: 35401820; PMCID: PMC8965502.
16. Driver C, Bamitale KDS, Kazi A, Olla M, Nyane NA, Owira PMO. Cardioprotective Effects of Metformin. J Cardiovasc Pharmacol. 2018 Aug;72(2):121-127. doi: 10.1097/FJC.0000000000000599. PMID: 29738369.
17. Lv Z, Guo Y. Metformin and Its Benefits for Various Diseases. Front Endocrinol (Lausanne). 2020 Apr 16;11:191. doi: 10.3389/fendo.2020.00191. PMID: 32425881; PMCID: PMC7212476.
18. Li JZ, Li YR. Cardiovascular Protection by Metformin: Latest Advances in Basic and Clinical Research. Cardiology. 2023;148(4):374-384. doi: 10.1159/000531432. Epub 2023 Jun 12. PMID: 37307806.
19. Foretz M, Guigas B, Viollet B. Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023 Aug;19(8):460-476. doi: 10.1038/s41574-023-00833-4. Epub 2023 May 2. PMID: 37130947; PMCID: PMC10153049.
20. Zhu L, Yang K, Ren Z, Yin D, Zhou Y. Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect. Transl Oncol. 2024 Jun;44:101945. doi: 10.1016/j.tranon.2024.101945. Epub 2024 Mar 30. PMID: 38555742; PMCID: PMC10998183.
21. Amengual-Cladera E, Morla-Barcelo PM, Morán-Costoya A, Sastre-Serra J, Pons DG, Valle A, Roca P, Nadal-Serrano M. Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies. Biology (Basel). 2024 Apr 27;13(5):302. doi: 10.3390/biology13050302. PMID: 38785784; PMCID: PMC11117706.
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