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Review

Metformin: a review of its potential indications

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Pages 2421-2429 | Published online: 22 Aug 2017

References

  • ScarpelloJHHowlettHCMetformin therapy and clinical usesDiab Vasc Dis Res200853 157 16718777488
  • InzucchiSEBergenstalRMBuseJBManagement of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)Diabetologia2012556 1577 159622526604
  • GrzybowskaMBoberJOlszewskaMMetformin – mechanisms of action and use for the treatment of type 2 diabetes mellitusPostepy Hig Med Dosw (Online)201165 277 28521677353
  • MatthaeiSGretenHEvidence that metformin ameliorates cellular insulin-resistance by potentiating insulin-induced translocation of glucose transporters to the plasma membraneDiabete Metab1991171 Pt 2 150 1581718789
  • ZhangBBZhouGLiCAMPK: an emerging drug target for diabetes and the metabolic syndromeCell Metab200995 407 41619416711
  • Diabetes Prevention Program Research GroupLong-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes StudyDiabetes Care2012354 731 73722442396
  • SalpeterSGreyberEPasternakGSalpeterERisk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitusCochrane Database Syst Rev20061 CD002967
  • GandiniSPuntoniMHeckman-StoddardBMMetformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confoundersCancer Prev Res (Phila)201479 867 88524985407
  • BannisterCAHoldenSEJenkins-JonesSCan 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 controlsDiabetes Obes Metab20141611 1165 117325041462
  • HongJZhangYLaiSSPREAD-DIMCAD InvestigatorsEffects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery diseaseDiabetes Care2013365 1304 131123230096
  • ChengCLinCHTsaiYWTsaiCJChouPHLanTHType 2 diabetes and antidiabetic medications in relation to dementia diagnosisJ Gerontol A Biol Sci Med Sci20146910 1299 130524899525
  • PatelRShahGEffect of metformin on clinical, metabolic and endocrine outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trialsCurr Med Res Opin2017 1 13
  • SchneiderMBMatsuzakiHHaorahJPrevention of pancreatic cancer induction in hamsters by metforminGastroenterology20011205 1263 127011266389
  • EvansJMDonnellyLAEmslie-SmithAMAlessiDRMorrisADMetformin and reduced risk of cancer in diabetic patientsBMJ20053307503 1304 130515849206
  • LeeMSHsuCCWahlqvistMLTsaiHNChangYHHuangYCType 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individualsBMC Cancer201111 2021241523
  • LibbyGDonnellyLADonnanPTAlessiDRMorrisADEvansJMNew users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetesDiabetes Care2009329 1620 162519564453
  • MonamiMColombiCBalziDMetformin and cancer occurrence in insulin-treated type 2 diabetic patientsDiabetes Care2011341 129 13120980415
  • LandmanGWKleefstraNvan HaterenKJGroenierKHGansROBiloHJMetformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16Diabetes Care2010332 322 32619918015
  • CoyleCCaffertyFHValeCLangleyREMetformin as an adjuvant treatment for cancer: a systematic review and meta-analysisAnn Oncol20162712 2184 219527681864
  • BodmerMBeckerCMeierCJickSSMeierCRUse of metformin and the risk of ovarian cancer: a case-control analysisGynecol Oncol20111232 200 20421802715
  • TsengCHMetformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitusDiabetes Metab Res Rev2015316 619 62625820555
  • JiralerspongSPallaSLGiordanoSHMetformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancerJ Clin Oncol20092720 3297 330219487376
  • CampagnoliCPasanisiPAbbàCEffect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized studyClin Breast Cancer2012123 175 18222607767
  • TsengCHMetformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitusEur J Cancer20145016 2831 283725201464
  • SehdevAShihYCVekhterBBissonnetteMBOlopadeOIPoliteBNMetformin for primary colorectal cancer prevention in patients with diabetes: a case-control study in a US populationCancer20151217 1071 107825424411
  • MazzonePJRaiHBeukemannMXuMJainASasidharMThe effect of metformin and thiazolidinedione use on lung cancer in diabeticsBMC Cancer201212 41022978440
  • LegaICAustinPCGruneirAGoodwinPJRochonPALipscombeLLAssociation between metformin therapy and mortality after breast cancer: a population-based studyDiabetes Care20133610 3018 302623633525
  • MargelDUrbachDLipscombeLLAssociation between metformin use and risk of prostate cancer and its gradeJ Natl Cancer Inst201310515 1123 113123853056
  • Mc MenaminÚCMurrayLJHughesCMCardwellCRMetformin use and survival after colorectal cancer: a population-based cohort studyInt J Cancer20161382 369 37926331456
  • WuLZhouBOshiro-RapleyNAn ancient, unified mechanism for metformin growth inhibition in C. elegans and cancerCell20161677 1705 171827984722
  • MoralesDRMorrisADMetformin in cancer treatment and preventionAnnu Rev Med201566 17 2925386929
  • GallagherEJLeRoithDDiabetes, cancer, and metformin: connections of metabolism and cell proliferationAnn N Y Acad Sci20111243 54 6822211893
  • DrazninBMechanism of the mitogenic influence of hyperinsulinemiaDiabetol Metab Syndr201131 1021668983
  • DingXZFehsenfeldDMMurphyLOPermertJAdrianTEPhysiological concentrations of insulin augment pancreatic cancer cell proliferation and glucose utilization by activating MAP kinase, PI3 kinase and enhancing GLUT-1 expressionPancreas2000213 310 32011039477
  • SachdevDYeeDDisrupting insulin-like growth factor signaling as a potential cancer therapyMol Cancer Ther200761 1 1217237261
  • GongJKelekarGShenJShenJKaurSMitaMThe expanding role of metformin in cancer: an update on antitumor mechanisms and clinical developmentTarget Oncol2016114 447 46726864078
  • MaJSawaiHMatsuoYIGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cellsJ Surg Res20101601 90 10119560785
  • AlgireCAmreinLBazileMDavidSZakikhaniMPollakMDiet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivoOncogene20113010 1174 118221102522
  • KourelisTVSiegelRDMetformin and cancer: new applications for an old drugMed Oncol2012292 1314 132721301998
  • DowlingRJNiraulaSStambolicVGoodwinPJMetformin in cancer: translational challengesJ Mol Endocrinol2012483 R31 R4322355097
  • ChiangGGAbrahamRTTargeting the mTOR signaling network in cancerTrends Mol Med20071310 433 44217905659
  • YoshidaSHongSSuzukiTRedox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathwayJ Biol Chem201128637 32651 3266021784859
  • InokiKZhuTGuanKLTSC2 mediates cellular energy response to control cell growth and survivalCell20031155 577 59014651849
  • JalvingMGietemaJALefrandtJDMetformin: taking away the candy for cancer?Eur J Cancer20104613 2369 238020656475
  • KalenderASelvarajAKimSYMetformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent mannerCell Metab2010115 390 40120444419
  • Ben SahraIRegazzettiCRobertGMetformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1Cancer Res20117113 4366 437221540236
  • ZhouGMyersRLiYRole of AMP-activated protein kinase in mechanism of metformin actionJ Clin Invest20011088 1167 117411602624
  • Lettieri BarbatoDVeglianteRDesideriECirioloMRManaging lipid metabolism in proliferating cells: new perspective for metformin usage in cancer therapyBiochim Biophys Acta201418452 317 32424569230
  • ErsoyCKiyiciSBudakFThe effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patientsDiabetes Res Clin Pract2008811 56 6018358555
  • HirschHAIliopoulosDStruhlKMetformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growthProc Natl Acad Sci U S A20131103 972 97723277563
  • EikawaSNishidaMMizukamiSYamazakiCNakayamaEUdonoHImmune-mediated antitumor effect by type 2 diabetes drug, metforminProc Natl Acad Sci U S A20151126 1809 181425624476
  • ChristensenKDoblhammerGRauRVaupelJWAgeing populations: the challenges aheadLancet20093749696 1196 120819801098
  • CabreiroFAuCLeungKYMetformin retards aging in C. elegans by altering microbial folate and methionine metabolismCell20131531 228 23923540700
  • Martin-MontalvoAMerckenEMMitchellSJMetformin improves healthspan and lifespan in miceNat Commun20134 219223900241
  • AnisimovVNBersteinLMPopovichIGIf started early in life, metformin treatment increases life span and postpones tumors in female SHR miceAging (Albany NY)201132 148 15721386129
  • Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) GroupLancet19983529131 854 8659742977
  • WuJWBoudreauDMParkYSimondsNIFreedmanANCommonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literatureExpert Opin Drug Saf2014138 1071 109924999107
  • SlackCFoleyAPartridgeLActivation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in DrosophilaPLoS One2012710 e4769923077661
  • LongoVDAntebiABartkeAInterventions to slow aging in humans: are we ready?Aging Cell2015144 497 51025902704
  • LiuBFanZEdgertonSMYangXLindSEThorADPotent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactionsCell Cycle20111017 2959 296621862872
  • BridgesHRJonesAJPollakMNHirstJEffects of metformin and other biguanides on oxidative phosphorylation in mitochondriaBiochem J20144623 475 48725017630
  • ZhengZChenHLiJSirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metforminDiabetes2012611 217 22822124463
  • LienFBerthierABouchaertEMetformin interferes with bile acid homeostasis through AMPK-FXR crosstalkJ Clin Invest20141243 1037 105124531544
  • LuJShiJLiMActivation of AMPK by metformin inhibits TGF-beta-induced collagen production in mouse renal fibroblastsLife Sci2015127 59 6525744403
  • DucaFACôtéCDRasmussenBAMetformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in ratsNat Med2015215 506 51125849133
  • NairVSreevalsanSBashaRMechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factorsJ Biol Chem201428940 27692 2770125143389
  • Pérez-RevueltaBIHettichMMCiociaroAMetformin lowers Ser-129 phosphorylated alpha-synuclein levels via mTOR-dependent protein phosphatase 2A activationCell Death Dis20145 e120924810045
  • SaishoYMetformin and inflammation: its potential beyond glucose-lowering effectEndocr Metab Immune Disord Drug Targets2015153 196 20525772174
  • SongYMLeeYHKimJWMetformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathwayAutophagy2015111 46 5925484077
  • BenjaminEJBlahaMJChiuveSEAmerican Heart Association Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics-2017 update: a report from the American Heart AssociationCirculation201713510 e146 e60328122885
  • HolmanRRPaulSKBethelMAMatthewsDRNeilHA10-Year follow-up of intensive glucose control in type 2 diabetesN Engl J Med200835915 1577 158918784090
  • RoumieCLHungAMGreevyRAComparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort studyAnn Intern Med20121579 601 61023128859
  • RousselRTravertFPasquetBReduction of Atherothrombosis for Continued Health (REACH) Registry InvestigatorsMetformin use and mortality among patients with diabetes and atherothrombosisArch Intern Med201017021 1892 189921098347
  • XuTBrandmaierSMessiasACEffects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetesDiabetes Care20153810 1858 186726251408
  • SeifarthCSchehlerBSchneiderHJEffectiveness of metformin on weight loss in non-diabetic individuals with obesityExp Clin Endocrinol Diabetes20131211 27 3123147210
  • FontbonneADioufIBaccara-DinetMEschwegeECharlesMAEffects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: a post-hoc analysis of the BIGPRO1 trialDiabetes Metab2009355 385 39119665415
  • MalinSKNightingaleJChoiSEChipkinSRBraunBMetformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adultsObesity (Silver Spring)2013211 93 10023505172
  • AdeyemoMAMcDuffieJRKozloskyMEffects of metformin on energy intake and satiety in obese childrenDiabetes Obes Metab2015174 363 37025483291
  • ZhouLLiuHWenXPengYTianYZhaoLEffects of metformin on blood pressure in nondiabetic patients: a meta-analysis of randomized controlled trialsJ Hypertens2017351 18 2627607453
  • ThomopoulosCKatsimagklisGMakrisTMetformin and blood pressure lowering: a questioned associationJ Hypertens2017351 27 2827902624
  • WanXHuoYJohnsM5′-AMP-activated protein kinase-activating transcription factor 1 cascade modulates human monocyte-derived macrophages to atheroprotective functions in response to heme or metforminArterioscler Thromb Vasc Biol20133311 2470 248024051143
  • IsodaKYoungJLZirlikAMetformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cellsArterioscler Thromb Vasc Biol2006263 611 61716385087
  • NgTPFengLYapKBLeeTSTanCHWinbladBLong-term metformin usage and cognitive function among older adults with diabetesJ Alzheimers Dis2014411 61 6824577463
  • HerathPMCherbuinNEramudugollaRAnsteyKJThe effect of diabetes medication on cognitive function: evidence from the PATH through life studyBiomed Res Int20162016 720842927195294
  • GuoMMiJJiangQMMetformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitusClin Exp Pharmacol Physiol2014419 650 65624862430
  • LuchsingerJAPerezTChangHMetformin in amnestic mild cognitive impairment: results of a pilot randomized placebo controlled clinical trialJ Alzheimers Dis2016512 501 51426890736
  • ImfeldPBodmerMJickSSMeierCRMetformin, other antidiabetic drugs, and risk of Alzheimer’s disease: a population-based case-control studyJ Am Geriatr Soc2012605 916 92122458300
  • MooreEMManderAGAmesDAIBL InvestigatorsIncreased risk of cognitive impairment in patients with diabetes is associated with metforminDiabetes Care20133610 2981 298724009301
  • KicksteinEKraussSThornhillPBiguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signalingProc Natl Acad Sci U S A201010750 21830 2183521098287
  • LiJDengJShengWZuoZMetformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant micePharmacol Biochem Behav20121014 564 57422425595
  • PiconePNuzzoDCaruanaLMetformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-kappaB activation: use of insulin to attenuate metformin’s effectBiochim Biophys Acta201518535 1046 105925667085
  • HettichMMMatthesFRyanDPThe anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complexPLoS One201497 e10242025025689
  • PoelsJSpasićMRCallaertsPNorgaKKExpanding roles for AMP-activated protein kinase in neuronal survival and autophagyBioessays2009319 944 95219644919
  • JinQChengJLiuYImprovement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental strokeBrain Behav Immun201440 131 14224632338
  • JiangTYuJTZhuXCAcute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre-activation of AMPK-dependent autophagyBr J Pharmacol201417113 3146 315724611741
  • VennaVRLiJHammondMDManciniNSMcCulloughLDChronic metformin treatment improves post-stroke angiogenesis and recovery after experimental strokeEur J Neurosci20143912 2129 213824649970
  • PintanaHApaijaiNPratchayasakulWChattipakornNChattipakornSCEffects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant ratsLife Sci20129111–12 409 41422925597
  • ZhaoRRXuXCXuFMetformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in miceBiochem Biophys Res Commun20144484 414 41724802403
  • AlzoubiKHKhabourOFAl-AzzamSITashtoushMHMhaidatNMMetformin eased cognitive impairment induced by chronic l-methionine administration: potential role of oxidative stressCurr Neuropharmacol2014122 186 19224669211
  • ChenFDongRRZhongKLAntidiabetic drugs restore abnormal transport of amyloid-beta across the blood-brain barrier and memory impairment in db/db miceNeuropharmacology2016101 123 13626211973
  • GuzickDPolycystic ovary syndrome: symptomatology, pathophysiology, and epidemiologyAm J Obstet Gynecol19981796 Pt 2 S89 S939855614
  • PasqualiRStener-VictorinEYildizBOPCOS Forum: research in polycystic ovary syndrome today and tomorrowClin Endocrinol (Oxf)2011744 424 43321158892
  • CarminaELoboRAUse of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndromeFertil Steril2004823 661 66515374711
  • DunaifAInsulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesisEndocr Rev1997186 774 8009408743
  • OvalleFAzzizRInsulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitusFertil Steril2002776 1095 110512057712
  • MoranLJMissoMLWildRANormanRJImpaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysisHum Reprod Update2010164 347 36320159883
  • LimSSDaviesMJNormanRJMoranLJOverweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysisHum Reprod Update2012186 618 63722767467
  • de GrootPCDekkersOMRomijnJADiebenSWHelmerhorstFMPCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysisHum Reprod Update2011174 495 50021335359
  • WildSPierpointTMcKeiguePJacobsHCardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort studyClin Endocrinol (Oxf)2000525 595 60010792339
  • VelazquezEMMendozaSHamerTSosaFGlueckCJMetformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancyMetabolism1994435 647 6548177055
  • MoghettiPCastelloRNegriCMetformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluationJ Clin Endocrinol Metab2000851 139 14610634377
  • GlueckCJWangPFontaineRTracyTSieve-SmithLMetformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS)J Adolesc Health2001293 160 16911524214
  • TangTLordJMNormanRJYasminEBalenAHInsulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertilityCochrane Database Syst Rev20125 CD003053
  • ShiQLiuSFonsecaVShiL72-OR / 72 - The effect of metformin exposure on neurodegenerative disease among elder adult veterans with diabetes mellitusAbstract presented at: Proceedings of the American Diabetes Association 76th Scientific SessionsJune 10–14; 2016New Orleans, LA