{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:12:20Z","timestamp":1793329940974,"version":"4.5.0"},"reference-count":87,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","diabetesresearchclinicalpractice.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Research and Clinical Practice"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1016\/j.diabres.2020.108025","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T11:23:01Z","timestamp":1579173781000},"page":"108025","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":84,"special_numbering":"C","title":["Metformin: An old drug against old age and associated morbidities"],"prefix":"10.1016","volume":"160","author":[{"given":"Teresa","family":"Salvatore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia Clara","family":"Pafundi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"Morgillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimondo","family":"Di Liello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Galiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Nevola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Marfella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Rinaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Elio","family":"Adinolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando Carlo","family":"Sasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9131","key":"10.1016\/j.diabres.2020.108025_b0005","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/S0140-6736(98)07037-8","article-title":"Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group","volume":"352","author":"UK Prospective Diabetes Study Group","year":"1998","journal-title":"Lancet"},{"key":"10.1016\/j.diabres.2020.108025_b0010","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"issue":"Suppl 1","key":"10.1016\/j.diabres.2020.108025_b0015","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2165\/00003495-199958001-00007","article-title":"Clinical efficacy of metformin against insulin resistance parameters: sinking the iceberg","volume":"58","author":"Zimmet","year":"1999","journal-title":"Drugs"},{"issue":"3","key":"10.1016\/j.diabres.2020.108025_b0020","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2174\/157016110791112359","article-title":"The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mellitus","volume":"8","author":"Anfossi","year":"2010","journal-title":"Curr Vasc Pharmacol"},{"issue":"10","key":"10.1016\/j.diabres.2020.108025_b0025","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.tips.2018.07.006","article-title":"Metformin as an Anticancer Agent","volume":"39","author":"Vancura","year":"2018","journal-title":"Trends Pharmacol Sci"},{"issue":"12","key":"10.1016\/j.diabres.2020.108025_b0030","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1007\/s11095-017-2199-y","article-title":"Metformin \u2013 a future therapy for neurodegenerative diseases: theme: drug discovery, development and delivery in Alzheimer's disease guest editor: Davide Brambilla","volume":"34","author":"Markowicz-Piasecka","year":"2017","journal-title":"Pharm Res"},{"key":"10.1016\/j.diabres.2020.108025_b0035","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arr.2017.08.003","article-title":"Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis","volume":"40","author":"Campbell","year":"2017","journal-title":"Ageing Res. Rev."},{"issue":"1","key":"10.1016\/j.diabres.2020.108025_b0040","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health effects of overweight and obesity in 195 countries over 25 years","volume":"377","author":"GBD 2015 Obesity Collaborators","year":"2017","journal-title":"N Engl J Med"},{"issue":"4","key":"10.1016\/j.diabres.2020.108025_b0045","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cger.2009.07.005","article-title":"The obesity paradox in the elderly: potential mechanisms and clinical implications","volume":"25","author":"Oreopoulos","year":"2009","journal-title":"Clin Geriatr Med"},{"issue":"5","key":"10.1016\/j.diabres.2020.108025_b0050","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/00325481.2019.1612150","article-title":"An opposing point of view on the obesity paradox","volume":"131","author":"Carbone","year":"2019","journal-title":"Postgrad Med"},{"key":"10.1016\/j.diabres.2020.108025_b0055","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1067\/mlc.2001.113504","article-title":"Sarcopenia","volume":"137","author":"Morley","year":"2001","journal-title":"J Lab Clin Med"},{"issue":"3","key":"10.1016\/j.diabres.2020.108025_b0060","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jjcc.2019.02.010","article-title":"Prognostic value of sarcopenic obesity estimated by computed tomography in patients with cardiovascular disease and undergoing surgery","volume":"74","author":"Yamashita","year":"2019","journal-title":"J Cardiol"},{"issue":"6","key":"10.1016\/j.diabres.2020.108025_b0065","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1001\/archinternmed.2009.20","article-title":"Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus","volume":"169","author":"Kooy","year":"2009","journal-title":"Arch Intern Med"},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0070","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s13679-019-00335-3","article-title":"Metformin: mechanisms in human obesity and weight loss","volume":"8","author":"Yerevanian","year":"2019","journal-title":"Curr Obes Rep."},{"key":"10.1016\/j.diabres.2020.108025_b0075","doi-asserted-by":"crossref","first-page":"e3173","DOI":"10.1002\/dmrr.3173","article-title":"Mechanisms of action of metformin with special reference to cardiovascular protection","volume":"25","author":"Zilov","year":"2019","journal-title":"Diabetes Metab Res Rev."},{"issue":"6","key":"10.1016\/j.diabres.2020.108025_b0080","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"N Engl J Med"},{"issue":"11","key":"10.1016\/j.diabres.2020.108025_b0085","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/S2213-8587(15)00291-0","article-title":"Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study","volume":"3","author":"Diabetes Prevention Program Research Group","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.diabres.2020.108025_b0090","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1007\/s40265-015-0416-8","article-title":"Therapeutic use of metformin in prediabetes and diabetes prevention","volume":"75","author":"Hostalek","year":"2015","journal-title":"Drugs"},{"issue":"6","key":"10.1016\/j.diabres.2020.108025_b0095","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.2337\/diabetes.52.6.1475","article-title":"Baltimore Longitudinal Study of Aging. The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging","volume":"52","author":"Meigs","year":"2003","journal-title":"Diabetes"},{"key":"10.1016\/j.diabres.2020.108025_b0100","doi-asserted-by":"crossref","first-page":"5S27","DOI":"10.1016\/S1262-3636(05)73649-1","article-title":"Diabetes mellitus in the elderly: insulin resistance and\/or impaired insulin secretion?","volume":"31","author":"Scheen","year":"2005","journal-title":"Diabetes Metab"},{"issue":"6","key":"10.1016\/j.diabres.2020.108025_b0105","doi-asserted-by":"crossref","first-page":"e4578","DOI":"10.7717\/peerj.4578","article-title":"Effect of metformin monotherapy on serum lipid profile in statin-na\u00efve individuals with newly diagnosed type 2 diabetes mellitus: a cohort study","volume":"12","author":"Lin","year":"2018","journal-title":"Peer J."},{"key":"10.1016\/j.diabres.2020.108025_b0110","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/HJH.0000000000001119","article-title":"Effects of metformin on blood pressure in nondiabetic patients: a meta-analysis of randomized controlled trials","volume":"35","author":"Zhou","year":"2017","journal-title":"J Hypertens"},{"issue":"15","key":"10.1016\/j.diabres.2020.108025_b0115","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1056\/NEJMoa0806470","article-title":"10-year follow-up of intensive glucose control in type 2 diabetes","volume":"359","author":"Holman","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.diabres.2020.108025_b0120","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.2337\/dc12-0719","article-title":"Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease","volume":"36","author":"Hong","year":"2013","journal-title":"Diabetes Care"},{"issue":"1","key":"10.1016\/j.diabres.2020.108025_b0125","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12933-019-0900-7","article-title":"Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis","volume":"18","author":"Han","year":"2019","journal-title":"Cardiovasc Diabetol."},{"issue":"11","key":"10.1016\/j.diabres.2020.108025_b0130","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/dom.12354","article-title":"Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls","volume":"16","author":"Bannister","year":"2014","journal-title":"Diabetes Obes Metab"},{"issue":"5","key":"10.1016\/j.diabres.2020.108025_b0135","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1161\/01.CIR.0000154542.13412.B1","article-title":"Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study","volume":"111","author":"Masoudi","year":"2005","journal-title":"Circulation"},{"issue":"1","key":"10.1016\/j.diabres.2020.108025_b0140","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1161\/CIRCHEARTFAILURE.110.952556","article-title":"Metformin use and mortality in ambulatory patients with diabetes and heart failure","volume":"4","author":"Aguilar","year":"2011","journal-title":"Circ Heart Fail."},{"issue":"3","key":"10.1016\/j.diabres.2020.108025_b0145","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1161\/CIRCHEARTFAILURE.112.000162","article-title":"Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients","volume":"6","author":"Eurich","year":"2013","journal-title":"Circ Heart Fail."},{"key":"10.1016\/j.diabres.2020.108025_b0150","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1001\/archinternmed.2010.409","article-title":"Reduction of atherothrombosis for continued health (REACH) registry investigators. Metformin use and mortality among patients with diabetes and atherothrombosis","volume":"170","author":"Roussel","year":"2010","journal-title":"Arch Intern Med"},{"issue":"3","key":"10.1016\/j.diabres.2020.108025_b0155","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.diabet.2013.02.006","article-title":"Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes","volume":"39","author":"Scheen","year":"2013","journal-title":"Diabetes Metab"},{"key":"10.1016\/j.diabres.2020.108025_b0160","doi-asserted-by":"crossref","first-page":"107879)","DOI":"10.1016\/j.diabres.2019.107879","article-title":"Metformin lactic acidosis: should we still be afraid?","volume":"157","author":"Salvatore","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"10.1016\/j.diabres.2020.108025_b0165","first-page":"ehz486","article-title":"ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD","author":"Cosentino","year":"2019","journal-title":"Eur Heart J"},{"key":"10.1016\/j.diabres.2020.108025_b0170","article-title":"Challenging 2019 ESC guidelines for the management of type 2 diabetes","author":"Scheen","year":"2019","journal-title":"Diabetes Metab"},{"issue":"10","key":"10.1016\/j.diabres.2020.108025_b0175","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.2337\/dc18-2356","article-title":"Effects of metformin therapy on coronary endothelial dysfunction in patients with prediabetes with stable angina and non-obstructive coronary artery stenosis: the CODYCE multicenter prospective study","volume":"42","author":"Sardu","year":"2019","journal-title":"Diabetes Care"},{"issue":"18","key":"10.1016\/j.diabres.2020.108025_b0180","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta22180","article-title":"Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT","volume":"22","author":"Griffin","year":"2018","journal-title":"Health Technol Assess"},{"issue":"9","key":"10.1016\/j.diabres.2020.108025_b0185","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s00125-017-4372-6","article-title":"Repurposing metformin for the prevention of cancer and cancer recurrence","volume":"60","author":"Heckman-Stoddard","year":"2017","journal-title":"Diabetologia"},{"issue":"11","key":"10.1016\/j.diabres.2020.108025_b0190","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1517\/13543784.2013.828691","article-title":"Metformin in lung cancer: rationale for a combination therapy","volume":"22","author":"Morgillo","year":"2013","journal-title":"Expert Opin Invest Drugs"},{"key":"10.1016\/j.diabres.2020.108025_b0195","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.3389\/fphys.2018.01039","article-title":"Molecular mechanisms of metformin for diabetes and cancer treatment","volume":"9","author":"Li","year":"2018","journal-title":"Front Physiol"},{"issue":"13","key":"10.1016\/j.diabres.2020.108025_b0200","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1158\/1078-0432.CCR-12-2777","article-title":"Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines","volume":"19","author":"Morgillo","year":"2013","journal-title":"Clin Cancer Res"},{"issue":"1","key":"10.1016\/j.diabres.2020.108025_b0205","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cllc.2014.06.010","article-title":"A multicenter, open-label phase II study of metformin with erlotinib in second-line therapy of stage IV non-small-cell lung cancer patients: treatment rationale and protocol dynamics of the METAL trial","volume":"16","author":"Fasano","year":"2015","journal-title":"Clin Lung Cancer"},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0210","doi-asserted-by":"crossref","first-page":"e000132","DOI":"10.1136\/esmoopen-2016-000132","article-title":"Results of the safety run-in part of the METAL (METformin in Advanced Lung cancer) study: a multicentre, open-label phase I-II study of metformin with erlotinib in second-line therapy of patients with stage IV non-small-cell lung cancer","volume":"2","author":"Morgillo","year":"2017","journal-title":"ESMO Open."},{"key":"10.1016\/j.diabres.2020.108025_b0215","doi-asserted-by":"crossref","first-page":"5911","DOI":"10.1038\/sj.onc.1210418","article-title":"Prevalence and specificity of LKB1 genetic alterations in lung cancers","volume":"26","author":"Matsumoto","year":"2007","journal-title":"Oncogene"},{"key":"10.1016\/j.diabres.2020.108025_b0220","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1002\/cncr.26151","article-title":"Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes","volume":"117","author":"Tan","year":"2011","journal-title":"Cancer"},{"issue":"1","key":"10.1016\/j.diabres.2020.108025_b0225","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/bcpt.12052","article-title":"Metformin induces cytotoxicity by down-regulating thymidine phosphorylase and excision repair cross-complementation 1 expression in non-small cell lung cancer cells","volume":"113","author":"Ko","year":"2013","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0230","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1165\/rcmb.2012-0244OC","article-title":"Metformin enhances cisplatin cytotoxicity by suppressing Stat3 activity independently of the LKB1-AMPK pathway","volume":"49","author":"Lin","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.diabres.2020.108025_b0235","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.bcp.2012.12.001","article-title":"Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel","volume":"85","author":"Tseng","year":"2013","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.diabres.2020.108025_b0240","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1158\/0008-5472.CAN-10-3471","article-title":"Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types","volume":"71","author":"Iliopoulos","year":"2011","journal-title":"Cancer Res"},{"issue":"4","key":"10.1016\/j.diabres.2020.108025_b0245","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.18632\/oncotarget.6559","article-title":"Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells","volume":"7","author":"Della Corte","year":"2016","journal-title":"Oncotarget."},{"key":"10.1016\/j.diabres.2020.108025_b0250","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1158\/2159-8290.CD-11-0280","article-title":"Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A","volume":"2","author":"Martin","year":"2012","journal-title":"Cancer Discov."},{"issue":"6","key":"10.1016\/j.diabres.2020.108025_b0255","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1056\/NEJMoa1215740","article-title":"Glucose levels and risk of dementia","volume":"369","author":"Crane","year":"2013","journal-title":"N Engl J Med"},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0260","doi-asserted-by":"crossref","first-page":"474","DOI":"10.2337\/diabetes.53.2.474","article-title":"Increased risk of type 2 diabetes in Alzheimer disease","volume":"53","author":"Janson","year":"2004","journal-title":"Diabetes"},{"key":"10.1016\/j.diabres.2020.108025_b0265","doi-asserted-by":"crossref","first-page":"100936S","DOI":"10.1016\/j.arr.2019.100936","article-title":"Diabetes drugs in the fight against Alzheimer's disease","volume":"54","author":"Boccardi","year":"2019","journal-title":"Ageing Res Rev"},{"issue":"9","key":"10.1016\/j.diabres.2020.108025_b0270","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fendo.2018.00400","article-title":"The therapeutic potential of metformin in neurodegenerative diseases","volume":"19","author":"Rotermund","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"10.1016\/j.diabres.2020.108025_b0275","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/gerona\/glu073","article-title":"Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis","volume":"69","author":"Cheng","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"18","key":"10.1016\/j.diabres.2020.108025_b0280","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1212\/WNL.0000000000004586","article-title":"Metformin vs sulfonylurea use and risk of dementia in US veterans aged \u226565 years with diabetes","volume":"89","author":"Orkaby","year":"2017","journal-title":"Neurology"},{"key":"10.1016\/j.diabres.2020.108025_b0285","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3233\/JAD-131901","article-title":"Long-term metformin usage and cognitive function among older adults with diabetes","volume":"41","author":"Ng","year":"2014","journal-title":"J Alzheimers Dis"},{"issue":"7","key":"10.1016\/j.diabres.2020.108025_b0290","doi-asserted-by":"crossref","first-page":"e024954","DOI":"10.1136\/bmjopen-2018-024954","article-title":"Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus","volume":"9","author":"Shi","year":"2019","journal-title":"BMJ Open."},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0295","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3233\/JAD-150493","article-title":"Metformin in amnestic mild cognitive impairment: results of a pilot randomized placebo controlled clinical trial","volume":"51","author":"Luchsinger","year":"2016","journal-title":"J Alzheimers Dis"},{"issue":"8","key":"10.1016\/j.diabres.2020.108025_b0300","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.mayocp.2019.01.004","article-title":"Metformin and sulfonylurea use and risk of incident dementia","volume":"94","author":"Scherrer","year":"2019","journal-title":"Mayo Clin Proc"},{"key":"10.1016\/j.diabres.2020.108025_b0305","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.pnpbp.2017.06.002","article-title":"Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus","volume":"79","author":"Kuan","year":"2017","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"key":"10.1016\/j.diabres.2020.108025_b0310","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.bbadis.2008.12.003","article-title":"brain aging, and cognition","volume":"1792","author":"Roriz-Filho","year":"2009","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"10.1016\/j.diabres.2020.108025_b0315","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0306-4522(00)00200-1","article-title":"Insulin-like growth factor-1 and insulin mediate transient site selective increases in tau phosphorylation in primary cortical neurons","volume":"99","author":"Lesort","year":"2000","journal-title":"Neuroscience"},{"key":"10.1016\/j.diabres.2020.108025_b0320","doi-asserted-by":"crossref","first-page":"5086","DOI":"10.1210\/en.2005-0063","article-title":"Tau is hyperphosphorylated in the insulin-like growth factor-I null brain","volume":"146","author":"Cheng","year":"2005","journal-title":"Endocrinology"},{"key":"10.1016\/j.diabres.2020.108025_b0325","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fmolb.2014.00009","article-title":"Differential effects of glycation on protein aggregation and amyloid formation","volume":"1","author":"Iannuzzi","year":"2014","journal-title":"Front Mol Biosci"},{"key":"10.1016\/j.diabres.2020.108025_b0330","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.3233\/JAD-170732","article-title":"A long journey into aging, brain aging, and Alzheimer\u2019s disease following the oxidative stress tracks","volume":"62","author":"Mecocci","year":"2018","journal-title":"J Alzheimer\u2019s Dis"},{"key":"10.1016\/j.diabres.2020.108025_b0335","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.bbadis.2016.08.018","article-title":"Is Alzheimer\u2019s disease a Type 3 diabetes? A critical appraisal","volume":"1863","author":"Kandimalla","year":"2018","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"10.1016\/j.diabres.2020.108025_b0340","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2174\/1871530315666150316124019","article-title":"Metformin and inflammation: its potential beyond glucose-lowering effect","volume":"15","author":"Saisho","year":"2015","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"10.1016\/j.diabres.2020.108025_b0345","doi-asserted-by":"crossref","first-page":"e102420","DOI":"10.1371\/journal.pone.0102420","article-title":"The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex","volume":"9","author":"Hettich","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.diabres.2020.108025_b0350","doi-asserted-by":"crossref","first-page":"21830","DOI":"10.1073\/pnas.0912793107","article-title":"Biguanide metformin acts on tau phosphorylation via mTOR\/protein phosphatase 2A (PP2A) signaling","volume":"107","author":"Kickstein","year":"2010","journal-title":"Proc Natl Acad Sci"},{"key":"10.1016\/j.diabres.2020.108025_b0355","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s11357-018-0042-y","article-title":"(2018) A framework for selection of blood based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup","volume":"40","author":"Justice","year":"2018","journal-title":"Geroscience"},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0360","doi-asserted-by":"crossref","first-page":"e12723","DOI":"10.1111\/acel.12723","article-title":"Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults","volume":"17","author":"Kulkarni","year":"2018","journal-title":"Aging Cell"},{"key":"10.1016\/j.diabres.2020.108025_b0365","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Lopez-Otin","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.diabres.2020.108025_b0370","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.mad.2013.11.002","article-title":"Metformin limits ceramide-induced senescence in C2C12 myoblasts","volume":"134","author":"Jadhav","year":"2013","journal-title":"Mech Ageing Dev"},{"key":"10.1016\/j.diabres.2020.108025_b0375","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/acel.12075","article-title":"Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK\/NF-kB activation","volume":"12","author":"Moiseeva","year":"2013","journal-title":"Aging Cell"},{"key":"10.1016\/j.diabres.2020.108025_b0380","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cell.2013.02.035","article-title":"Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism","volume":"153","author":"Cabreiro","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.diabres.2020.108025_b0385","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.tem.2016.08.003","article-title":"Linking the microbiota, chronic disease, and the immune system","volume":"27","author":"Hand","year":"2016","journal-title":"Trends Endocrinol Metab"},{"key":"10.1016\/j.diabres.2020.108025_b0390","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.2337\/db10-0351","article-title":"Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice","volume":"60","author":"Xie","year":"2011","journal-title":"Diabetes"},{"key":"10.1016\/j.diabres.2020.108025_b0395","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10863-006-9003-8","article-title":"The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin","volume":"38","author":"Batandier","year":"2006","journal-title":"J Bioenerg Biomembr"},{"issue":"9","key":"10.1016\/j.diabres.2020.108025_b0400","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3389\/fendo.2018.00657","article-title":"Metformin is a direct SIRT1-activating compound: computational modeling and experimental validation","volume":"6","author":"Cuy\u00e0s","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"10.1016\/j.diabres.2020.108025_b0405","doi-asserted-by":"crossref","first-page":"e8758","DOI":"10.1371\/journal.pone.0008758","article-title":"Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans health-span via AMPK, LKB1, and SKN-1","volume":"5","author":"Onken","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.diabres.2020.108025_b0410","doi-asserted-by":"crossref","DOI":"10.1016\/j.tem.2019.07.015","article-title":"Metformin as anti-aging therapy: is it for everyone?","author":"Soukas","year":"2019","journal-title":"Trends Endocrinol Metab"},{"key":"10.1016\/j.diabres.2020.108025_b0415","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.cmet.2010.03.014","article-title":"Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner","volume":"11","author":"Kalender","year":"2010","journal-title":"Cell Metab"},{"key":"10.1016\/j.diabres.2020.108025_b0420","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.cmet.2016.12.009","article-title":"Metformin inhibits hepatic mtorc1 signaling via dose-dependent mechanisms involving ampk and the tsc complex","volume":"25","author":"Howell","year":"2017","journal-title":"Cell Metab"},{"issue":"7","key":"10.1016\/j.diabres.2020.108025_b0425","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2016.11.055","article-title":"An ancient, unified mechanism for metformin growth inhibition in C elegans and cancer","volume":"167","author":"Wu","year":"2016","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.diabres.2020.108025_b0430","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.cell.2008.11.037","article-title":"Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells","volume":"136","author":"D'Angelo","year":"2009","journal-title":"Cell"},{"issue":"e3126825","key":"10.1016\/j.diabres.2020.108025_b0435","first-page":"71","article-title":"Metformin extends C. elegans lifespan through lysosomal pathway","volume":"6","author":"Chen","year":"2017","journal-title":"Elife"}],"container-title":["Diabetes Research and Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168822719317930?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168822719317930?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:11:03Z","timestamp":1759173063000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168822719317930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":87,"alternative-id":["S0168822719317930"],"URL":"https:\/\/doi.org\/10.1016\/j.diabres.2020.108025","relation":{},"ISSN":["0168-8227"],"issn-type":[{"value":"0168-8227","type":"print"}],"subject":[],"published":{"date-parts":[[2020,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metformin: An old drug against old age and associated morbidities","name":"articletitle","label":"Article Title"},{"value":"Diabetes Research and Clinical Practice","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.diabres.2020.108025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108025"}}