Skip to content
2000
Volume 20, Issue 3
  • ISSN: 1574-8863
  • E-ISSN: 2212-3911

Abstract

This extensive review delves into the complex relationship between prolonged use of metformin and the possible emergence of vitamin B12 deficiency (VB12D) in diabetic patients. Metformin, a pivotal element in diabetes management, is constantly linked with decreased absorption of vitamin B12, prompting concerns about the enduring consequences of this interaction. The review systematically amalgamates current evidence, elucidating the prevalence, mechanisms, and clinical ramifications of VB12D induced by consistent consumption of metformin. Exploring the different pathways through which metformin might disrupt the absorption of Vitamin B12, the review encompasses interference with the calcium-dependent membrane activity and alterations of the microbiota present in the gut. A meticulous analysis of experimental studies and human trials is undertaken, accentuating the prevalence of variable VB12D among individuals on long-duration treatment of metformin across diverse populations and age groups. Clinical indications of cobalamin deficiency, spanning haematological abnormalities to neurological complications, are systematically examined. Furthermore, the review delves into the potential implications of cobalamin deficiency associated with metformin on diabetes-related complications and overall patient health. This review offers a comprehensive overview of the intricate interplay between the use of metformin and deficiency of vitamin B12 in diabetic patients, emphasizing the importance that lies in routine monitoring, early detection, and personalized interventions to optimize the long-period safety and efficiency of metformin in the treatment of diabetes. It also proposes future research directions to refine clinical guidelines and enhance the understanding regarding the correlation between diabetes, metformin, and vitamin B12.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cds/10.2174/0115748863308106240816044733
2024-08-28
2025-10-03

  • From This Site

    /content/journals/cds/10.2174/0115748863308106240816044733
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. CloeteL. Diabetes mellitus: An overview of the types, symptoms, complications and management.Nurs. Stand.2022371616610.7748/ns.2021.e11709 34708622
     [Google Scholar]
  2. KumariR. KaurJ. HussainS. Management of diabetes with COVID-19: A review.Int. J. Pharm. Pharm. Sci.202012121610.22159/ijpps.2020v12i12.39968
     [Google Scholar]
  3. KaulK TarrJ M AhmadS I KohnerE M ChibberR. Diabetes: an old disease, a new insight2013
     [Google Scholar]
  4. RefardtJ. WinzelerB. Christ-CrainM. Diabetes Insipidus.Endocrinol. Metab. Clin. North Am.202049351753110.1016/j.ecl.2020.05.012 32741486
     [Google Scholar]
  5. BahlG. UpadhyayD.K. VarmaM. SinghR. DasS. HussainM.S. Chronic calcific pancreatitis presented with secondary diabetes and diabetic ketoacidosis: A case report.Clinical Diabetology202312320921110.5603/DK.a2023.0015
     [Google Scholar]
  6. ArnethB. ArnethR. ShamsM. Metabolomics of type 1 and type 2 diabetes.Int. J. Mol. Sci.20192010246710.3390/ijms20102467 31109071
     [Google Scholar]
  7. JinQ. MaR.C.W. Metabolomics in diabetes and diabetic complications: Insights from epidemiological studies.Cells20211011283210.3390/cells10112832 34831057
     [Google Scholar]
  8. PalumboC. NicolaciN. La MannaA.A. BranekN. PissanoM.N. [Association between central diabetes insipidus and type 2 diabetes mellitus]. Medicina (B. Aires)2018782127130 29659364
     [Google Scholar]
  9. VyasG. KarpeS. GuptaK. Threads of hope: Harnessing nanofibres-based treatment strategies for diabetic foot ulcers.J. Drug Deliv. Sci. Technol.2023912105225
     [Google Scholar]
  10. WildS. RoglicG. GreenA. SicreeR. KingH. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030.Diabetes Care20042751047105310.2337/diacare.27.5.1047 15111519
     [Google Scholar]
  11. ChoN.H. ShawJ.E. KarurangaS. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045.Diabetes Res. Clin. Pract.201813827128110.1016/j.diabres.2018.02.023 29496507
     [Google Scholar]
  12. SeoH.J. OhH.S. Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: A nationwide sample cohort study in Korea using extended landmark time analysis.Epidemiol. Health202143202110310.4178/epih.e2021103 34922421
     [Google Scholar]
  13. MahabaleshwarkarR. LiuT.L. MulderH. Comparative effectiveness of metformin dosage uptitration versus adding another antihyperglycemic medication on glycemic control in type 2 diabetes patients failing initial metformin monotherapy: A retrospective cohort study.Popul. Health Manag.201922545746310.1089/pop.2018.0158 30628868
     [Google Scholar]
  14. OhT.K. SongI.A. Metformin use and the risk of cancer in patients with diabetes: A nationwide sample cohort study.Cancer Prev. Res. (Phila.)202013219520210.1158/1940‑6207.CAPR‑19‑0427 31699707
     [Google Scholar]
  15. PernicovaI. KorbonitsM. Metformin—mode of action and clinical implications for diabetes and cancer.Nat. Rev. Endocrinol.201410314315610.1038/nrendo.2013.256 24393785
     [Google Scholar]
  16. DamanhouriZ.A. AlkreathyH.M. AlharbiF.A. AbualhamailH. AhmadM.S. A Review of the impact of pharmacogenetics and metabolomics on the efficacy of metformin in type 2 diabetes.Int. J. Med. Sci.202320114215010.7150/ijms.77206 36619226
     [Google Scholar]
  17. BahlG. HussainM.S. SaraswatN. AgrawalM. Beyond diabetes management: Unraveling metformin’s long-term effects on vitamin B12.Clinical Diabetology202312527928210.5603/cd.97473
     [Google Scholar]
  18. SchweighoferN. StrasserM. ObermayerA. Identification of novel intronic snps in transporter genes associated with metformin side effects.Genes (Basel)2023148160910.3390/genes14081609 37628660
     [Google Scholar]
  19. YazidiM. KamounE. Hadj TaiebS. Vitamin B12 deficiency in long-term metformin treated type 2 diabetic patients: Prevalence and risk factors in a Tunisian population.Chronic Illn.202320231742395323118422010.1177/17423953231184220 37337655
     [Google Scholar]
  20. ArodaV.R. EdelsteinS.L. GoldbergR.B. Long-term metformin use and vitamin b12 deficiency in the diabetes prevention program outcomes study.J. Clin. Endocrinol. Metab.201610141754176110.1210/jc.2015‑3754 26900641
     [Google Scholar]
  21. SanjayC.J. PatilK. NagabhushanaD. PandaR. MahimaV.G. Long-term use of metformin and its effect on serum vitamin B12 with its oral manifestations: A review.J. Clin. Diagn. Res.20221631610.7860/JCDR/2022/53256.16055
     [Google Scholar]
  22. AgiusL. FordB.E. ChachraS.S. The metformin mechanism on gluconeogenesis and ampk activation: the metabolite perspective.Int. J. Mol. Sci.2020219324010.3390/ijms21093240 32375255
     [Google Scholar]
  23. WasnerH.K. Metformin’s mechanism of action is stimulation of the biosynthesis of the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP).Int. J. Mol. Sci.2022234220010.3390/ijms23042200 35216316
     [Google Scholar]
  24. ZhangL.Y. YinY.H. WangX.J. Advances in the mechanism of action of metformin in pituitary tumors.World J. Metaanal.202311514415010.13105/wjma.v11.i5.144
     [Google Scholar]
  25. HussainM.S. GuptaG. GoyalA. From nature to therapy: Luteolin’s potential as an immune system modulator in inflammatory disorders.J. Biochem. Mol. Toxicol.202337112348210.1002/jbt.23482 37530602
     [Google Scholar]
  26. KumarH. ChakrabartiA. SarmaP. Novel therapeutic mechanism of action of metformin and its nanoformulation in Alzheimer’s disease and role of AKT/ERK/GSK pathway.Eur. J. Pharm. Sci.202318110634810.1016/j.ejps.2022.106348 36496166
     [Google Scholar]
  27. BuseJ.B. DeFronzoR.A. RosenstockJ. The primary glucose-lowering effect of metformin resides in the gut, not the circulation: results from short-term pharmacokinetic and 12-week dose-ranging studies.Diabetes Care201639219820510.2337/dc15‑0488 26285584
     [Google Scholar]
  28. TanJ. WangY. LiuS. Long-acting metformin vs. metformin immediate release in patients with type 2 diabetes: A systematic review.Front. Pharmacol.20211266981410.3389/fphar.2021.669814 34079464
     [Google Scholar]
  29. Tarry-AdkinsJ.L. GrantI.D. OzanneS.E. ReynoldsR.M. AikenC.E. Efficacy and side effect profile of different formulations of metformin: A systematic review and meta-analysis.Diabetes Ther.20211271901191410.1007/s13300‑021‑01058‑2 34075573
     [Google Scholar]
  30. PanagouliasG.S. DoupisJ. Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination.Patient Prefer. Adherence20148227236 24627627
     [Google Scholar]
  31. DerosaG. MaffioliP. Patient considerations and clinical utility of a fixed dose combination of saxagliptin/metformin in the treatment of type 2 diabetes.Diabetes Metab. Syndr. Obes.2011426327110.2147/DMSO.S16361 21792325
     [Google Scholar]
  32. WatanabeF. BitoT. Vitamin B12 sources and microbial interaction.Exp. Biol. Med. (Maywood)2018243214815810.1177/1535370217746612 29216732
     [Google Scholar]
  33. BanjariI. HjartåkerA. Dietary sources of iron and vitamin B12: Is this the missing link in colorectal carcinogenesis?Med. Hypotheses201811610511010.1016/j.mehy.2018.05.003 29857891
     [Google Scholar]
  34. GilleD. SchmidA. Vitamin B12 in meat and dairy products.Nutr. Rev.201573210611510.1093/nutrit/nuu011 26024497
     [Google Scholar]
  35. RizzoG. LaganàA. RapisardaA. Vitamin B12 among vegetarians: status, assessment and supplementation.Nutrients201681276710.3390/nu8120767 27916823
     [Google Scholar]
  36. Salcedo-BellidoI. Martínez-GalianoJ. Olmedo-RequenaR. Association between vitamin intake during pregnancy and risk of small for gestational age.Nutrients2017912127710.3390/nu9121277 29168736
     [Google Scholar]
  37. TsiroukidouK. PaschalidouE.G. GrammatikopoulouM.G. Serum concentrations and dietary intake of vitamin B12 in children and adolescents on metformin: A case–control study.Int. J. Mol. Sci.2023244420510.3390/ijms24044205 36835611
     [Google Scholar]
  38. WiedemanA.M. DhillonA.K. WuB.T. InnisS.M. ElangoR. DevlinA.M. Children aged 5–6 years in vancouver, canada meet dietary recommendations for folate and vitamin b12 but not choline.J. Nutr.2023153119720710.1016/j.tjnut.2022.11.012 36913454
     [Google Scholar]
  39. GharibzahediS.M.T. MoghadamM. AmftJ. TolunA. HasabnisG. AltintasZ. Recent advances in dietary sources, health benefits, emerging encapsulation methods, food fortification, and new sensor-based monitoring of vitamin B12: A critical review.Molecules20232822746910.3390/molecules28227469 38005191
     [Google Scholar]
  40. SolimanM. Tawfik. Study on the production of vitamin B12 by newly isolated and identified pseudomonas aeruginosa and effect of gamma irradiation on fermentation substrate.Arab J Nuc Sci App202356410711610.21608/ajnsa.2023.184230.1705
     [Google Scholar]
  41. HussainM.S. SharmaG. The Burden of cardiovascular diseases due to COVID-19 pandemic.Thorac. Cardiovasc. Surg.20247214050 35987194
     [Google Scholar]
  42. BhaiyyaM. PattnaikP.K. GoelS. Electrochemiluminescence sensing of vitamin B12 using laser-induced graphene based bipolar and single electrodes in a 3D-printed portable system.Microfluid. Nanofluidics20212554110.1007/s10404‑021‑02442‑x
     [Google Scholar]
  43. KumarR. SinghU. TiwariA. TiwariP. SahuJ.K. SharmaS. Vitamin B12: Strategies for enhanced production, fortified functional food products and health benefits.Process Biochem.2023127445510.1016/j.procbio.2023.02.002
     [Google Scholar]
  44. BellD.S.H. Metformin‐induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes.Diabetes Obes. Metab.20222481423142810.1111/dom.14734 35491956
     [Google Scholar]
  45. KakarlapudiY. KondaboluS.K. TehseenZ. Effect of metformin on vitamin b12 deficiency in patients with type 2 diabetes mellitus and factors associated with it: A meta-analysis.Cureus202214123227710.7759/cureus.32277 36628003
     [Google Scholar]
  46. KhattabR. AlbannawiM. AlhajjmohammedD. Metformin-induced vitamin B12 deficiency among type 2 diabetes mellitus’ patients: A systematic review.Curr. Diabetes Rev.202319411010.2174/1573399818666220418080959 35440313
     [Google Scholar]
  47. AlhajiJ.H. Vitamin B12 deficiency in patients with diabetes on metformin: Arab countries.Nutrients20221410204610.3390/nu14102046 35631186
     [Google Scholar]
  48. TaşÖ. KontbayT. DoganO. Does metformin treatment in pediatric population cause vitamin b12 deficiency?Klin. Padiatr.2022234422122710.1055/a‑1702‑2614 35114702
     [Google Scholar]
  49. TomkinG.H. Comparison of the effect of parenteral with oral biguanide therapy on vitamin B12 and bile acid absorption.Ir. J. Med. Sci.1976145134034710.1007/BF02938968
     [Google Scholar]
  50. AlachkarA. NattoufA-H. The effect of metformin on absorption of vitamin B12, folic acid, iron, albumin and calcium in syrian patients.Age (Omaha)2014252142144
     [Google Scholar]
  51. InfanteM. LeoniM. CaprioM. FabbriA. Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind.World J. Diabetes202112791693110.4239/wjd.v12.i7.916 34326945
     [Google Scholar]
  52. AhmedM.A. Metformin and vitamin B12 deficiency: Where do we stand?J. Pharm. Pharm. Sci.201619338239810.18433/J3PK7P 27806244
     [Google Scholar]
  53. Di MagnoL. Di PastenaF. BordoneR. ConiS. CanettieriG. The mechanism of action of biguanides: New answers to a complex question.Cancers (Basel)20221413322010.3390/cancers14133220 35804992
     [Google Scholar]
  54. AlmatrafiS.B. BakrE.S.H. AlmatrafiA.A. AltayebM.M. Prevalence of vitamin B12 deficiency and its association with metformin-treated type 2 diabetic patients: A cross sectional study.Human Nut Meta20222720013810.1016/j.hnm.2022.200138
     [Google Scholar]
  55. Al QuranT. KhaderA. AllanH. Prevalence of vitamin B12 deficiency in type 2 diabetic patients taking metformin, a cross-sectional study in primary healthcare.Front. Endocrinol. (Lausanne)202314122679810.3389/fendo.2023.1226798 37732117
     [Google Scholar]
  56. OwhinS.O. AdajaT.M. FasipeO.J. AkhidenoP.E. KalejaiyeO.O. KehindeM.O. Prevalence of vitamin B 12 deficiency among metformin-treated type 2 diabetic patients in a tertiary institution, South-South Nigeria.SAGE Open Med.2019710.1177/2050312119853433 31205703
     [Google Scholar]
  57. KhanA. Shafiq’I. Hassan ShahM. Prevalence of vitamin B12 deficiency in patients with type II diabetes mellitus on metformin: a study from Khyber Pakhtunkhwa.Cureus201798157710.7759/cureus.1577 29057189
     [Google Scholar]
  58. KimJ. AhnC.W. FangS. LeeH.S. ParkJ.S. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes.Medicine (Baltimore)201998461791810.1097/MD.0000000000017918 31725641
     [Google Scholar]
  59. BaigF.A. KhanS. RizwanA. Frequency of vitamin B12 deficiency in type 2 diabetic patients taking metformin.Cureus20221432292410.7759/cureus.22924 35399475
     [Google Scholar]
  60. WuH.H.L. McDonnellT. ChinnaduraiR. Physiological associations between vitamin B deficiency and diabetic kidney disease.Biomedicines2023114115310.3390/biomedicines11041153 37189771
     [Google Scholar]
  61. BelloC.T. CapitãoR.M. DuarteJ.S. AzinheiraJ. VasconcelosC. Défice de vitamina B12 na diabetes mellitus tipo 2.Acta Med. Port.2017301071972610.20344/amp.8860 29268066
     [Google Scholar]
  62. KhalafK.M. KhudhairM.S. AshorA.W. Vitamin B12 status and peripheral neuropathy in patients with type 2 diabetes mellitus.J. Pak. Med. Assoc.20196984044
     [Google Scholar]
  63. Raheel IftikharR.I. KamranS. Adnan QadirA.Q. Zohaib IqbalZ.I. Hassan UsmanH.U. Prevalence of vitamin B12 deficinecy in patients of type 2 diabetes mellitus on metformin: a case control study from Pakistan.Pan Afr. Med. J.20131667
     [Google Scholar]
  64. PratamaS. LaurenB.C. WisnuW. The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review.Diabetes Metab. Syndr.2022161010263410.1016/j.dsx.2022.102634 36240684
     [Google Scholar]
  65. MercantepeF. Relationship of vitamin B12 levels with different degrees of obesity and diabetes mellitus.Cureus202315104735210.7759/cureus.47352 38021783
     [Google Scholar]
  66. LanganR.C. GoodbredA.J. Vitamin B12 deficiency: Recognition and management.Am. Fam. Physician2017966384389 28925645
     [Google Scholar]
  67. ShiptonM.J. ThachilJ. Vitamin B12 deficiency – A 21st century perspective.Clin. Med. (Lond.)201515214515010.7861/clinmedicine.15‑2‑145 25824066
     [Google Scholar]
  68. HasbaouiB.E. MebroukN. SaghirS. YajouriA.E. AbilkassemR. AgadrA. Vitamin B12 deficiency: Case report and review of literature.Pan Afr. Med. J.2021381237 34046142
     [Google Scholar]
  69. AlrumaikhaniF. RabbaniU. Knowledge and practice of physicians about vitamin B12 deficiency among type 2 diabetes mellitus patients in buraidah, saudi arabia.J Cont Med Sci20228410.22317/jcms.v8i4.1209
     [Google Scholar]
  70. MallaD. BajracharyaM.R. KarkiB.B. RajouriaA.D. ShresthaP.S. Prevalence of vitamin B12 deficiency in patients with type II diabetes mellitus on metformin.J Diab Endo Asso Nepal202151394310.3126/jdean.v5i1.38916
     [Google Scholar]
  71. KrishnamoorthyA. Study of vitamin b12 deficiency in patients with type 2 diabetes mellitus.Int. J. Sci. Stud.202193176178
     [Google Scholar]
  72. VargheseN. Clinical and haematological manifestations of vitamin b12 deficiency in type 2 diabetic patients treated with metformin-a comparative study2017
     [Google Scholar]
  73. TingR.Z.W. SzetoC.C. ChanM.H-M. MaK.K. ChowK.M. Risk factors of vitamin B(12) deficiency in patients receiving metformin.Arch. Intern. Med.2006166181975197910.1001/archinte.166.18.1975 17030830
     [Google Scholar]
  74. AhmedM.A. MuntinghG. RheederP. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.BMC Pharmacol. Toxicol.20161714410.1186/s40360‑016‑0088‑3 27716423
     [Google Scholar]
  75. PetriM. SinghI. BakerC. UnderkoflerC. RasouliN. Diabetic gastroparesis: An overview of pathogenesis, clinical presentation and novel therapies, with a focus on ghrelin receptor agonists.J. Diabetes Complications202135210773310.1016/j.jdiacomp.2020.107733 32948398
     [Google Scholar]
  76. Ibba ManneschiL. PaciniS. CorsaniL. BechiP. Faussone-PellegriniM.S. Interstitital cells of cajal in the human stomach: Distribution and relationship with enteric innervation.Histol. Histopathol.200419411531164 15375758
     [Google Scholar]
  77. GoyalR.K. GuoY. MashimoH. Advances in the physiology of gastric emptying.Neurogastroenterol. Motil.20193141354610.1111/nmo.13546 30740834
     [Google Scholar]
  78. CamilleriM. BharuchaA.E. FarrugiaG. Epidemiology, mechanisms, and management of diabetic gastroparesis.Clin. Gastroenterol. Hepatol.20119151210.1016/j.cgh.2010.09.022 20951838
     [Google Scholar]
  79. DockrayG.J. Gastrointestinal hormones and the dialogue between gut and brain.J. Physiol.2014592142927294110.1113/jphysiol.2014.270850 24566540
     [Google Scholar]
  80. CaturanoA. CavalloM. NiloD. Diabetic gastroparesis: navigating pathophysiology and nutritional interventions.Gastrointestinal Disorders20246121422910.3390/gidisord6010016
     [Google Scholar]
  81. BennettM. Megaloblastic Anaemia.J. R. Coll. Phys. Edinb.202050446110.4997/JRCPE.2020.430 33469636
     [Google Scholar]
  82. TorrezM. Chabot-RichardsD. BabuD. LockhartE. FoucarK. How I investigate acquired megaloblastic anemia.Int. J. Lab. Hematol.202244223624710.1111/ijlh.13789 34981651
     [Google Scholar]
  83. YangW. CaiX. WuH. JiL. Associations between metformin use and vitamin B 12 levels, anemia, and neuropathy in patients with diabetes: a meta‐analysis.J. Diabetes201911972974310.1111/1753‑0407.12900 30615306
     [Google Scholar]
  84. AngelousiA. LargerE. Anaemia, a common but often unrecognized risk in diabetic patients: A review.Diabetes Metab.2015411182710.1016/j.diabet.2014.06.001 25043174
     [Google Scholar]
  85. DonnellyL.A. DennisJ.M. ColemanR.L. Risk of anemia with metformin use in type 2 diabetes: A MASTERMIND study.Diabetes Care202043102493249910.2337/dc20‑1104 32801130
     [Google Scholar]
  86. AlbaiO. TimarB. PaunD.L. SimaA. RomanD. TimarR. Metformin treatment: A potential cause of megaloblastic anemia in patients with type 2 diabetes mellitus.Diabetes Metab. Syndr. Obes.2020133873387810.2147/DMSO.S270393 33116733
     [Google Scholar]
  87. CallaghanT.S. HaddenD.R. TomkinG.H. Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment.BMJ198028062251214121510.1136/bmj.280.6225.1214 7388472
     [Google Scholar]
  88. GuptaK. JainA. RohatgiA. An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.Diabetes Metab. Syndr.2018121515810.1016/j.dsx.2017.08.014 28882470
     [Google Scholar]
  89. NiafarM. HaiF. PorhomayonJ. NaderN.D. The role of metformin on vitamin B12 deficiency: A meta-analysis review.Intern. Emerg. Med.20151019310210.1007/s11739‑014‑1157‑5 25502588
     [Google Scholar]
  90. AlvarezM. SierraO.R. SaavedraG. MorenoS. Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: A cross-sectional study.Endocr. Connect.20198101324132910.1530/EC‑19‑0382 31518991
     [Google Scholar]
  91. HansenC.S. Lundby-ChristiansenL. TarnowL. Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: Substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial.Cardiovasc. Diabetol.202019115010.1186/s12933‑020‑01131‑3 32979921
     [Google Scholar]
  92. ChowdhuryM. NevittS. EleftheriadouA. Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: A meta-analysis.BMJ Open Diabetes Res. Care202192248010.1136/bmjdrc‑2021‑002480 34969689
     [Google Scholar]
  93. PorterK.M. WardM. HughesC.F. Hyperglycemia and metformin use are associated with B vitamin deficiency and cognitive dysfunction in older adults.J. Clin. Endocrinol. Metab.2019104104837484710.1210/jc.2018‑01791 30920623
     [Google Scholar]
  94. BiemansE. HartH.E. RuttenG.E.H.M. Cuellar RenteriaV.G. Kooijman-BuitingA.M.J. BeulensJ.W.J. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin.Acta Diabetol.201552238339310.1007/s00592‑014‑0661‑4 25315630
     [Google Scholar]
  95. MooreE.M. ManderA.G. AmesD. Increased risk of cognitive impairment in patients with diabetes is associated with metformin.Diabetes Care201336102981298710.2337/dc13‑0229 24009301
     [Google Scholar]
  96. DidangelosT. KarlaftiE. KotzakioulafiE. Vitamin B12 supplementation in diabetic neuropathy: A 1-year, randomized, double-blind, placebo-controlled trial.Nutrients202113239510.3390/nu13020395 33513879
     [Google Scholar]
  97. ChappellL. BrownS.A. WenselT.M. Evaluation of vitamin B12 monitoring in patients on concomitant metformin and proton pump inhibitors.Innov. Pharm.2020114510.24926/iip.v11i4.3355 34007643
     [Google Scholar]
  98. MazokopakisE.E. StarakisI.K. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency.Diabetes Res. Clin. Pract.201297335936710.1016/j.diabres.2012.06.001 22770998
     [Google Scholar]
  99. ChaudharyA.T. Shiraz AliA. Vitamin B-12 deficiency in type 2 diabetes patients on metformin therapy–A narrative review Middle East J.Fam. Med.20232184454
     [Google Scholar]
  100. CelaC. LangusM. Prevalence of low and borderline levels of vitamin b12 in type 2 diabetic patients treated with metformin: A cross-sectional study in Argentina.Diabetes2020691
     [Google Scholar]
  101. RambliR. AznidaF.A.A. Azimatun NoorA. Benefits and challenges of teleconsultation service for non-communicable disease follow-up in public healthcare clinics in Malaysia: a qualitative study.Med. J. Malaysia2023784449457 37518911
     [Google Scholar]
  102. SabbaghR. ShahN. JenkinsS. The COVID-19 pandemic and follow-up for shoulder surgery: The impact of a shift toward telemedicine on validated patient-reported outcomes.J. Telemed. Telecare202329648449110.1177/1357633X21990997 33525951
     [Google Scholar]
  103. ParrettiH.M. HughesC.A. JonesL.L. ‘The rollercoaster of follow‐up care’ after bariatric surgery: A rapid review and qualitative synthesis.Obes. Rev.20192018810710.1111/obr.12764 30345630
     [Google Scholar]
  104. MelnykB.M. Fineout-OverholtE. GigglemanM. ChoyK. A test of the ARCC© model improves implementation of evidence‐based practice, healthcare culture, and patient outcomes.Worldviews Evid. Based Nurs.20171415910.1111/wvn.12188 28002651
     [Google Scholar]
  105. SheikhY. AliA. KhasatiA. Benefits and challenges of video consulting for mental health diagnosis and follow-up: A qualitative study in community care.Int. J. Environ. Res. Public Health2023203259510.3390/ijerph20032595 36767957
     [Google Scholar]
  106. RiisC.L. BechmannT. JensenP.T. CoulterA. SteffensenK.D. Are patient-reported outcomes useful in post-treatment follow-up care for women with early breast cancer? A scoping review.Patient Relat. Outcome Meas.20191011712710.2147/PROM.S195296 30988648
     [Google Scholar]
  107. GrassoM.A. HamunimeN. MaherA.D. Improving the benefits of HIV testing and referrals in large household surveys through active linkages to care: Lessons and recommendations from the Namibia population-based HIV impact assessment (NAMPHIA), 2017.AIDS Care202133101308131110.1080/09540121.2021.1874266 33486974
     [Google Scholar]
  108. PerforsI.A.A. HelsperC.W. NoteboomE.A. van der WallE. de WitN.J. MayA.M. Randomised controlled trial protocol (GRIP study): examining the effect of involvement of a general practitioner and home care oncology nurse after a cancer diagnosis on patient reported outcomes and healthcare utilization.BMC Cancer201818113210.1186/s12885‑018‑4005‑6 29402234
     [Google Scholar]
  109. TherawiwatM. ImameeN. JaiuaD. Effects of a 4D pro-gram on blood sugar control among patients with type 2 diabetes in Pathumthani Province.J. Public Health Dent.2022201110
     [Google Scholar]
  110. MangahasT. HuangG. NeherJ.O. SafranekS. Does metformin prevent diabetes in at-risk adults?J. Fam. Pract.2013628436437
     [Google Scholar]
  111. Preventing type 2 diabetes: lifestyle changes work better than drugs.Health News2002846 11989457
     [Google Scholar]
  112. ApolzanJ.W. VendittiE.M. EdelsteinS.L. Long-term weight loss with metformin or lifestyle intervention in the diabetes prevention program outcomes study.Ann. Intern. Med.20191701068269010.7326/M18‑1605 31009939
     [Google Scholar]
  113. Top ways to reduce your risk of developing diabetes.Mayo Clin. Health Lett.20102894 20925157
     [Google Scholar]
  114. MaysE.P.Jr Increasing vitamin B12 screening among patients with type 2 diabetes on long-term metformin therapy.Clin. Diabetes202139442442610.2337/cd20‑0108 34866784
     [Google Scholar]
  115. KumarS. Comparison of safety and efficacy of glimepiride-metformin and vildagliptin- metformin treatment in newly diagnosed type 2 diabetic patients.Indian J. Endocrinol. Metab.202125432633110.4103/ijem.ijem_276_21 35136740
     [Google Scholar]
  116. SedeeqS.T. MohamedZ A K. Al FehaidiA A S. Review for the management of vitamin B12 deficiency in diabetic patients on metformin.Int J Res Med Sci2020810.18203/2320‑6012.ijrms20203091
     [Google Scholar]
  117. JeonH.J. OhT.K. Comparison of vildagliptin-metformin and glimepiride-metformin treatments in type 2 diabetic patients.Diabetes Metab. J.201135552953510.4093/dmj.2011.35.5.529 22111045
     [Google Scholar]
  118. WalkerE.A. GonzalezJ.S. TripputiM.T. Long-term metformin adherence in the diabetes prevention program outcomes study.BMJ Open Diabetes Res. Care202081153710.1136/bmjdrc‑2020‑001537 33023898
     [Google Scholar]
  119. Bazo-AlvarezJ.C. PalK. PhamT.M. NazarethI. PetersenI. SharmaM. Cardiovascular outcomes of type 2 diabetic patients treated with DPP 4 inhibitors versus sulphonylureas as add-on to metformin in clinical practice.Sci. Rep.20211112382610.1038/s41598‑021‑02670‑9 34903733
     [Google Scholar]
/content/journals/cds/10.2174/0115748863308106240816044733
Loading
Long-Term Use of Metformin and Vitamin B12 Deficiency in Diabetes
Curr Drug Saf 20, 258 (2025); https://doi.org/10.2174/0115748863308106240816044733
/content/journals/cds/10.2174/0115748863308106240816044733
/content/journals/cds/10.2174/0115748863308106240816044733
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): anaemia; cubilin receptors; diabetes; metformin; neuropathy; Vitamin B12

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test