Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45:2753–86. https://doi.org/10.2337/dci22-0034.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lv ZQ, Guo YJ. Metformin and its benefits for various diseases. Front Endocrinol (Lausanne). 2020;11:191. https://doi.org/10.3389/fendo.2020.00191.

Article  PubMed  Google Scholar 

Morales DR, Morris AD. Metformin in cancer treatment and prevention. Annu Rev Med. 2015;66:17–29. https://doi.org/10.1146/annurev-med-062613-093128.

Article  PubMed  CAS  Google Scholar 

Breining P, Jensen JB, Sundelin EI, Gormsen LC, Jakobsen S, Busk M, et al. Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro. Diabetes Obes Metab. 2018;20:2264–73. https://doi.org/10.1111/dom.13362.

Article  PubMed  CAS  Google Scholar 

Dihoum A, Rena G, Pearson ER, Lang CC, Mordi IR. Metformin: evidence from preclinical and clinical studies for potential novel applications in cardiovascular disease. Expert Opin Investig Drugs. 2023;32:291–9. https://doi.org/10.1080/13543784.2023.2196010.

Article  PubMed  CAS  Google Scholar 

Chen QY, Zhang HY, Yang YM, Zhang SM, Wang J, Zhang DW, et al. Metformin attenuates UVA-Induced skin Photoaging by suppressing mitophagy and the PI3K/AKT/mTOR pathway. Int J Mol Sci. 2022;23:6960. https://doi.org/10.3390/ijms23136960.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chai M, Jiang MS, Vergnes L, Fu XD, de Barros SC, Doan NB, et al. Stimulation of hair growth by small molecules that activate autophagy. Cell Rep. 2019;27:3413–e34213. https://doi.org/10.1016/j.celrep.2019.05.070.

Article  PubMed  CAS  Google Scholar 

Sun C, Hu SH, Dong BQ, Jiang S, Miao F, Lei TC. Metformin promotes the hair-inductive activity of three-dimensional aggregates of epidermal and dermal cells self-assembled in vitro. Skin Pharmacol Physiol. 2022;35:137–47. https://doi.org/10.1159/000521400.

Article  PubMed  CAS  Google Scholar 

Lehraiki A, Abbe P, Cerezo M, Rouaud F, Regazzetti C, Chignon-Sicard B, et al. Inhibition of melanogenesis by the antidiabetic Metformin. J Invest Dermatol. 2014;134:2589–97. https://doi.org/10.1038/jid.2014.202.

Article  PubMed  CAS  Google Scholar 

Moon J, Lee S-Y, Choi JW, Lee AR, Yoo JH, Moon S-J, et al. Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts. J Transl Med. 2021;19:192. https://doi.org/10.1186/s12967-021-02860-z.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chang J-E, Choi MS. A molecular perspective on the potential benefits of Metformin for the treatment of inflammatory skin disorders. Int J Mol Sci. 2020;21:8960. https://doi.org/10.3390/ijms21238960.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shi LL, Jiang ZY, Li JQ, Lin H, Xu B, Liao XC, et al. Metformin improves burn wound healing by modulating microenvironmental fibroblasts and macrophages. Cells. 2022;11:4094. https://doi.org/10.3390/cells11244094.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Tombulturk FK, Soydas T, Kanigur-Sultuybek G. Topical metformin accelerates wound healing by promoting collagen synthesis and inhibiting apoptosis in a diabetic wound model. Int Wound J. 2024;21:e14345. https://doi.org/10.1111/iwj.14345.

Article  PubMed  Google Scholar 

Hedayatyanfard K, Niazi S, Hesami S, S N, Tavakoli-Far B, Bayat G, et al. Metformin ointment may relieve hypertrophic and keloid scars. Australas J Dermatol. 2023;64:565–7. https://doi.org/10.1111/ajd.14165.

Kropp M, Golubnitschaja O, Mazurakova A, Koklesova L, Sargheini N, Vo T-TKS, et al. Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation. EPMA J. 2023;14:21–42. https://doi.org/10.1007/s13167-023-00314-8.

Article  PubMed  PubMed Central  Google Scholar 

Singer AJ. Healing mechanisms in cutaneous wounds: tipping the balance. Tissue Engineering Part B: Reviews. 2022;28:1151–67. https://doi.org/10.1089/ten.TEB.2021.0114.

Article  PubMed  CAS  Google Scholar 

Falanga V, Isseroff RR, Soulika AM, Romanelli M, Margolis D, Kapp S, et al. Chronic wounds. Nat Rev Dis Primers. 2022;8:50. https://doi.org/10.1038/s41572-022-00377-3.

Article  PubMed  PubMed Central  Google Scholar 

Chen S-H, Kuo H-J, Chou P-Y, Tsai C-H, Chen S-H, Yao Y-C, et al. Engineered, radially Aligned, Gradient-Metformin-Eluting nanofiber dressings accelerate Burn-Wound healing. Int J Nanomed. 2024;19:11463–77. https://doi.org/10.2147/IJN.S492244.

Article  CAS  Google Scholar 

Zeng ZY, Jiang GH, Sun YF, Aharodnikau UE, Yunusov KE, Gao XF. Rational design of flexible microneedles coupled with CaO2@PDA-loaded nanofiber films for skin wound healing on diabetic rats. Biomater Sci. 2022;10:5326–39. https://doi.org/10.1039/d2bm00861k.

Article  PubMed  CAS  Google Scholar 

Chen S, Gan DH, Lin SX, Zhong YM, Chen MJ, Zou XN, et al. Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms. Theranostics. 2022;12:2722–40. https://doi.org/10.7150/thno.71360.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Vancura A, Bu P, Bhagwat M, Zeng J, Vancurova I. Metformin as an anticancer agent. Trends Pharmacol Sci. 2018;39:867–78. https://doi.org/10.1016/j.tips.2018.07.006.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Casarella A, Nicotera R, Zicarelli MT, Urso A, Presta P, Deodato F, et al. Autosomic dominant polycystic kidney disease and metformin: old knowledge and new insights on retarding progression of chronic kidney disease. Med Res Rev. 2022;42:629–40. https://doi.org/10.1002/med.21850.

Article  PubMed  CAS  Google Scholar 

Li KY, Tam CHT, Liu H, Day S, Lim CKP, So WY, et al. DNA methylation markers for kidney function and progression of diabetic kidney disease. Nat Commun. 2023;14:2543. https://doi.org/10.1038/s41467-023-37837-7.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Nadiger N, Veed JK, Chinya Nataraj P, Mukhopadhyay A. DNA methylation and type 2 diabetes: a systematic review. Clin Epigenetics. 2024;16:67. https://doi.org/10.1186/s13148-024-01670-6.

Article  PubMed  PubMed Central  Google Scholar 

Morze J, Wittenbecher C, Schwingshackl L, Danielewicz A, Rynkiewicz A, Hu FB, et al. Metabolomics and type 2 diabetes risk: an updated systematic review and meta-analysis of prospective cohort studies. Diabetes Care. 2022;45:1013–24. https://doi.org/10.2337/dc21-1705.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bonnefond A, Unnikrishnan R, Doria A, Vaxillaire M, Kulkarni RN, Mohan V, et al. Monogenic diabetes. Nat Rev Dis Primers. 2023;9:12. https://doi.org/10.1038/s41572-023-00421-w.

Article  PubMed  Google Scholar 

Long JL, Fang QS, Shi Z, Miao ZH, Yan D. Integrated biomarker profiling for predicting the response of type 2 diabetes to Metformin. Diabetes Obes Metabolism. 2024;26(8):3439–47. https://doi.org/10.1111/dom.15689.

Article  CAS  Google Scholar 

Chen Z-Z, Gerszten RE. Metabolomics and proteomics in type 2 diabetes. Circ Res. 2020;126:1613–27. https://doi.org/10.1161/CIRCRESAHA.120.315898.

Article  PubMed  PubMed Central  CAS