Effects of metformin on oral lesions
Abstract
Metformin is a biguanide antidiabetic drug used to treat type 2 diabetes. It has a beneficial effect on insulin resistance, but
it also reduces the oncogenetic effect of tumor cells at several points of attack, reducing oxidative stress and the body’s
inflammatory reactions. In our study, we sought to answer the question, based on a review of the literature, on whether
and in what way metformin affects oral lesions. From our PubMed and Google Scholar database, 26 studies form the basis
of our publication, primarily reporting on the effects of metformin on periodontitis and head and neck malignancies and
discussing the association between these diseases and diabetes. In clinical trials of several years, non-diabetic patients
with chronic periodontitis showed that topical administration of 1% metformin improved patients’ inflammatory reactions
and reduced bone loss. In diabetic patients, systemic administration of metformin had a beneficial effect on periodontal
status. When metformin is administered systemically, it reduces the oncogenetic effect of tumor cells via various signaling
pathways. Publications have shown that systemically administered metformin also reduces the incidence of malignancies
in head and neck tumor patients, increases the efficacy of radiotherapy and chemotherapy, and improves tumor
survival in both diabetic and non-diabetic patients. Several authors suggest the use of metformin as a complementary
treatment to support traditional cancer therapies.
References
AKRAM Z, VOHRA F, JAVED F: Locally delivered metformin as adjunct to scaling and root planing in the treatment of periodontal defects: A systematic review and meta-analysis. J Periodontal Res 2018; 53:941-949. https://doi.org/10.1111/jre.12573
BOSETTI C, CARIOLI G, SANTUCCI C, BERTUCCIO P, GALLUS S, GARAVELLO W, et al.: Global trends in oral and pharyngeal cancer incidence and mortality. Int J Cancer 2020; 147:1040-1049. https://doi.org/10.1002/ijc.32871
CURRY JM, JOHNSON J, MOLLAEE M, TASSONE P, AMIN D, KNOPS A, et al.: Metformin clinical trial in HPV+ and HPV- head and neck squamous cell carcinoma: Impact on cancer cell apoptosis and immune infiltrate. Front Oncol 2018; 8. https://doi.org/10.3389/fonc.2018.00436
DE ARAÚJO AA, DE SOUSA BARBOSA FREITAS PEREIRA A, DE MEDEIROS CACX, DE CASTRO BRITO GA, DE CARVALHO LEITAO RF, DE SOUZA ARAÚJO L, et al.: Effects of metformin on inammation, oxidative stress, and bone loss in a rat model of periodontitis. PLoS One 2017; 12:e0183506. https://doi.org/10.1371/journal.pone.0183506
DE OLIVEIRA FIGUEIREDO RA, WEIDERPASS E, TAJARA EH, STRÖM P, CARVALHO AL, DE CARVALHO MB, KANDA JL, et al.: Diabetes mellitus, metformin and head and neck cancer. Oral Oncol 2016; 61:47-54. https://doi.org/10.1016/j.oraloncology.2016.08.006
DIZ P, MELETI M, DINIZ-FREITAS M, VESCOVI P, WARNAKULASURIYA S, JOHNSON NW, KERR AR: Oral and pharyngeal cancer in europe. Translational Research in Oral Oncology 2017; 2:2057178X1770151. https://doi.org/10.1177/2057178X17701517
FOX CH: New considerations in the prevalence of periodontal disease. Curr Opin Dent 1992; 2:5-11
FOX CH, JETTE AM, MCGUIRE SM, FELDMAN HA, DOUGLASS CW: Periodontal disease among New England elders. J Periodontol 1994; 65:676-684 https://doi.org/10.1902/jop.1994.65.7.676
JANG WG, KIM EJ, BAE IH, LEE KN, KIM YD, KIM DK, et al.: Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of runx2. Bone 2011; 48:885-893. https://doi.org/10.1016/j.bone.2010.12.003
KÉKES E: A 2-es típusú diabetes előfordulása a világban, Európában és Magyarországon. Hypertonia és Nephrologia 2020; 24:32-34. https://doi.org/10.33668/HN.24.011
KELLY M, STEELE J, NUTTALL N et. al.: The condition of supporting structures. In: Walker A, Cooper I (eds.) Adult dental health survey: oral health in the United Kingdom 1998. The Stationery Office, London, 2000; pp 123-146
NICOLINI, GRISA TA, MUNIZ FWMG, RÖSING CK, CAVAGNI J: Effect of adjuvant use of metformin on periodontal treatment: a systematic review and meta-analysis. Clin Oral Investig 2018; 23:2659-2666. https://doi.org/10.1007/s00784-018-2666-9
PRADEEP A, RAO NS, NAIK SB, KUMARI M: Efficacy of varying concentrations of subgingivally delivered metformin in the treatment of chronic periodontitis: A randomized controlled clinical trial. J Periodontol 2013; 84:212-220. https://doi.org/10.1902/jop.2012.120025
PRESHAW PM, ALBA AL, HERRERA D, JEPSEN S, KONSTANTINIDIS A, MAKRILAKIS K, et al.: Periodontitis and diabetes: a two-way relationship. Diabetologia 2011; 55:21-31. https://doi.org/10.1007/s00125-011-2342-y
RAO NS, PRADEEP A, KUMARI M, NAIK SB: LOCALLY DELIVERED 1% METFORMIN GEL IN THE TREATMENT OF SMOKERS WITH CHRONIC PERIODONTITIS: A randomized controlled clinical trial. J Periodontol 2013; 84:1165-1171. https://doi.org/10.1902/jop.2012.120298
REGO DF, PAVAN LMC, ELIAS ST, CANTO GDL, GUERRA ENS: Effects of metformin on head and neck cancer: A systematic review. Oral Oncol 2015; 51:416-422. https://doi.org/10.1016/j.oraloncology.2015.01.007
SARAEI P, ASADI I, KAKAR MA, MORADI-KOR N: The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag Res 2019; Volume 11:3295-3313. https://doi.org/10.2147/CMAR.S200059
SKINNER HD, SANDULACHE VC, OW TJ, MEYN RE, YORDY JS, BEADLE BM, et al.: TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res 2011; 18:290-300. https://doi.org/10.1158/1078-0432.CCR-11-2260
STOKES WA, EGUCHI M, AMINI A, HARARAH MK, DING D, MCDERMOTT JD, et al.: Survival impact and toxicity of metformin in head and neck cancer: An analysis of the SEER-medicare dataset. Oral Oncol 2018; 84:12-19. https://doi.org/10.1016/j.oraloncology.2018.06.022
SUN X, LI M, XIA L, FANG Z, YU S, GAO J, et al.: Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment. Sci Rep 2020; 10. https://doi.org/10.1038/s41598-020-72035-1
UJPÁL M, MATOS O, BÍBOK G, SZABÓ G: A diabetes mellitus előfordulása malignus szájüregi daganatos betegekben. Orv Hetil 2002; 143:2731-2733. ISSN 0030-6002.
WANG X, WANG H, ZHANG T, CAI L, DAI E, HE J: Diabetes and its potential impact on head and neck oncogenesis. J Cancer 2020; 11:583-591. https://doi.org/10.7150/jca.35607
WERNER EA, BELL J: The preparation of methylguanidine, and of ββ-dimethylguanidine by the interaction of dicyanodiamide, and methylammonium and dimethylammonium chlorides respectively. J Chem Soc Trans 1992; 121:1790-1794 https://doi.org/10.1039/CT9222101790
WINKLER G: Metformin - Újabb adatok egy megbízható és hatékony ,,régi" vércukorcsökkentő készítményről. Orvosi Hetilap 2016; 157:882-891. https://doi.org/10.1556/650.2016.30485
YEN YC, LIN C, LIN SW, LIN YS, WENG SF: Effect of metformin on the incidence of head and neck cancer in diabetics. Head Neck 2014; 37:1268-1273. https://doi.org/10.1002/hed.23743
https://idf.org/our-network/regions-members/europe/members/138-hungary.html (2021.09.21.)
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