Advantages of the use of metformin in patients with impaired uric acid metabolism
- Authors: Eliseev M.S.1, Panevin T.S.1, Zhelyabina O.V.1, Nasonov E.L.1,2
-
Affiliations:
- Nasonova Research Institute of Rheumatology
- Sechenov First Moscow State Medical University (Sechenov University)
- Issue: Vol 93, No 5 (2021)
- Pages: 628–634
- Section: Reviews
- URL: https://journals.rcsi.science/0040-3660/article/view/71520
- DOI: https://doi.org/10.26442/00403660.2021.05.200795
- ID: 71520
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Abstract
Metformin is one of the oldest and at the same time relevant and effective drugs for the treatment of type 2 diabetes. At the same time, the mechanism of the hypoglycemic effect was not completely clear until recently. Current data suggest that the mechanism of action of metformin contributes to the development of an anti-inflammatory effect, as well as a decrease in the level of uric acid, and its use can be potentially useful in patients with hyperuricemia and gout.
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##article.viewOnOriginalSite##About the authors
Maksim S. Eliseev
Nasonova Research Institute of Rheumatology
Email: elicmax@rambler.ru
ORCID iD: 0000-0003-1191-5831
SPIN-code: 2524-7320
канд. мед. наук, ст. науч. сотр
Russian Federation, MoscowTaras S. Panevin
Nasonova Research Institute of Rheumatology
Author for correspondence.
Email: tarasel@list.ru
ORCID iD: 0000-0002-5290-156X
SPIN-code: 7839-3145
канд. мед. наук, врач-эндокринолог
Russian Federation, MoscowOlga V. Zhelyabina
Nasonova Research Institute of Rheumatology
Email: olga-sheliabina@mail.ru
ORCID iD: 0000-0002-5394-7869
SPIN-code: 8038-6195
мл. науч. сотр.
Russian Federation, MoscowEvgeny L. Nasonov
Nasonova Research Institute of Rheumatology; Sechenov First Moscow State Medical University (Sechenov University)
Email: nasonov@irramn.ru
ORCID iD: 0000-0002-1598-8360
акад. РАН, д-р мед. наук, проф., науч. рук. ФГБНУ, проф. ФГАОУ ВО
Russian Federation, Moscow; MoscowReferences
- Zhang Y, Yamamoto T, Hisatome I, et al. Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic β cells. Mol Cell Endocrinol. 2013;375(1-2):89-96. doi: 10.1016/j.mce.2013.04.027
- Lanaspa MA, Cicerchi C, Garcia G, et al. Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver. PLoS One. 2012;7(11):e48801. doi: 10.1371/journal.pone.0048801
- Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67(5):1739-42.doi: 10.1111/j.1523-1755.2005.00273.x
- Johnson RJ, Perez-Pozo SE, Sautin YY, et al. Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Endocr Rev. 2009;30(1):96-116. doi: 10.1210/er.2008-0033
- Matsuoka T, Kajimoto Y, Watada H, et al. Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells. J Clin Invest. 1997;99(1):144-50. doi: 10.1172/JCI119126
- Facchini F, Chen YD, Hollenbeck CB, Reaven GM. Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA. 1991;266(21):3008-11. doi: 10.1001/jama.1991.03470210076036
- Muscelli E, Natali A, Bianchi S, et al. Effect of insulin on renal sodium and uric acid handling in essential hypertension. Am J Hypertens. 1996;9(8):746-52. doi: 10.1016/0895-7061(96)00098-2
- Dehghan A, van Hoek M, Sijbrands EJ, et al. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care. 2008;31(2):361-2. doi: 10.2337/dc07-1276
- Kodama S, Saito K, Yachi Y, et al. Association between serum uric acid and development of type 2 diabetes. Diabetes Care. 2009;32(9):1737-42. doi: 10.2337/dc09-0288
- Lai HM, Chen CJ, Su BY, et al. Gout and type 2 diabetes have a mutual inter-dependent effect on genetic risk factors and higher incidences. Rheumatology (Oxford). 2012;51(4):715-20. doi: 10.1093/rheumatology/ker373
- Nakagawa T, Hu H, Zharikov S, et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2006;290(3):F625-31. doi: 10.1152/ajprenal.00140.2005
- Sánchez-Lozada LG, Tapia E, Bautista-García P, et al. Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2008;294(4):F710-8. doi: 10.1152/ajprenal.00454.2007
- Паневин Т.С., Желябина О.В., Елисеев М.С., Шестакова М.В. Уратснижающие эффекты ингибиторов дипептидилпептидазы-4. Сахарный диабет. 2020;23(4):349-56 [Panevin TS, Zhelyabina OV, Eliseev MS, Shestakova MV. Urate-lowering effects of dipeptidyl peptidase-4 inhibitors. Diabetes Mellitus. 2020;23(4):349-56 (in Russian)]. doi: 10.14341/DM12412
- Паневин Т.С., Елисеев М.С., Шестакова М.В., Насонов Е.Л. Преимущества терапии ингибиторами натрий-глюкозного котранспортера 2-го типа у пациентов с сахарным диабетом 2-го типа в сочетании с гиперурикемией и подагрой. Терапевтический архив. 2020;92(5):110-8 [Panevin TS, Eliseev MS, Shestakova MV, Nasonov EL. Advantages of therapy with sodium glucose cotransporter type 2 inhibitors in patients with type 2 diabetes mellitus in combination with hyperuricemia and gout. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(5):110-8 (in Russian)]. doi: 10.26442/00403660.2020.05.000633
- Bailey CJ. Metformin: historical overview. Diabetologia. 2017;60(9):1566-76. doi: 10.1007/s00125-017-4318-z
- Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 9-й вып. Сахарный диабет. 2019;22(1S1):1-144 [Dedov II, Shestakova MV, Mayorov AY, et al. Standards of specialized diabetes care. 9th ed. Diabetes Mellitus. 2019;22(1S1):1-144 (in Russian)]. doi: 10.14341/dm221s1
- Aroda VR, Knowler WC, Crandall JP, et al. Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetologia. 2017;60(9):1601-11. doi: 10.1007/s00125-017-4361-9
- Дедов И.И., Шестакова М.В., Викулова О.К., и др. Атлас регистра сахарного диабета Российской Федерации. Статус 2018 г. Сахарный диабет. 2019;22(2S):4-61 [Dedov II, Shestakova MV, Vikulova OK, et al. Atlas of Diabetes Register in Russian Federation, status 2018. Diabetes Mellitus. 2019;22(2S):4-61 (in Russian)]. doi: 10.14341/dm12208
- Sharma M, Nazareth I, Petersen I. Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study. BMJ Open. 2016;6(1):e010210. doi: 10.1136/bmjopen-2015-010210
- DeFronzo RA, Stonehouse AH, Han J, Wintle ME. Relationship of baseline HbA1c and efficacy of current glucose-lowering therapies: a meta-analysis of randomized clinical trials. Diabet Med. 2010;27(3):309-17. doi: 10.1111/j.1464-5491.2010.02941
- Zhou K, Yee SW, Seiser EL, et al. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet. 2016;48(9):1055-9. doi: 10.1038/ng.3632
- Domecq JP, Prutsky G, Leppin A, et al. Drugs Commonly Associated With Weight Change: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2015;100(2):363-70. doi: 10.1210/jc.2014-3421
- UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854-65. doi: 10.1016/s0140-6736(98)07037-8
- Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017;60(9):1620-9. doi: 10.1007/s00125-017-4337-9
- U.K. Prospective Diabetes Study Group. U.K. Prospective Diabetes Study 16: overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995;44:1249-58. doi: 10.2337/diabetes.44.11.1249
- Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin. Diabetes Care. 2006;29(2):254-8. doi: 10.2337/diacare.29.02.06.dc05-1558
- Salpeter S, Greyber E, Pasternak G, Salpeter E. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2003. doi: 10.1002/14651858.cd002967
- Connelly PJ, Lonergan M, Soto-Pedre E, et al. Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: A GoDarts study. Diabetes Obes Metab. 2017;19(11):1579-86. doi: 10.1111/dom.12978
- Coperchini F, Leporati P, Rotondi M, Chiovato L. Expanding the therapeutic spectrum of metformin: from diabetes to cancer. J Endocrinol Invest. 2015;38(10):1047-55. doi: 10.1007/s40618-015-0370-z
- Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577-85. doi: 10.1007/s00125-017-4342-z
- Anabtawi A, Miles JM. Metformin: nonglycemic effects and potential novel indications. Endocr Pract. 2016;22(8):999-1007. doi: 10.4158/ep151145.ra
- Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016;23(6):1060-5. doi: 10.1016/j.cmet.2016.05.011
- Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348(3):607-14. doi: 10.1042/bj3480607
- Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2010;12(1):21-35. doi: 10.1038/nrm3025
- Lin HH, Chang KT, Hung CC, et al. Effects of the mTOR inhibitor Rapamycin on Monocyte-Secreted Chemokines. BMC Immunol. 2014;15(1). doi: 10.1186/s12865-014-0037-0
- Vazirpanah N, Ottria A, van der Linden M, et al. mTOR inhibition by metformin impacts monosodium urate crystal-induced inflammation and cell death in gout: a prelude to a new add-on therapy? Ann Rheum Dis. 2019;78(5):663-71. doi: 10.1136/annrheumdis-2018-214656
- Saleiro D, Platanias LC. Intersection of mTOR and STAT signaling in immunity. Trends Immunol. 2015;36(1):21-9. doi: 10.1016/j.it.2014.10.006
- Ursini F, Russo E, Pellino G, et al. Metformin and Autoimmunity: A “New Deal” of an Old Drug. Front Immunol. 2018;9. doi: 10.3389/fimmu.2018.01236
- O’Neill LAJ, Hardie DG. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature. 2013;493(7432):346-55. doi: 10.1038/nature11862
- Kelly B, Tannahill GM, Murphy MP, O’Neill LAJ. Metformin Inhibits the Production of Reactive Oxygen Species from NADH: Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1β (IL-1β) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages. J Biol Chem. 2015;290(33):20348-59. doi: 10.1074/jbc.m115.662114
- Bułdak Ł, Machnik G, Bułdak RJ, et al. Exenatide and metformin express their anti-inflammatory effects on human monocytes/macrophages by the attenuation of MAPKs and NFκB signaling. Naunyn Schmiedeberg Arch Pharmacol. 2016;389(10):1103-15. doi: 10.1007/s00210-016-1277-8
- Krysiak R, Gdula-Dymek A, Okopień B. Monocyte-suppressing effect of high-dose metformin in fenofibrate-treated patients with impaired glucose tolerance. Pharmacol Rep. 2013;65(5):1311-6. doi: 10.1016/s1734-1140(13)71489-0
- Krysiak R, Okopien B. The effect of metformin on monocyte secretory function in simvastatin-treated patients with impaired fasting glucose. Metabolism. 2013;62(1):39-43. doi: 10.1016/j.metabol.2012.06.009
- Cameron AR, Morrison VL, Levin D, et al. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016;119(5):652-65. doi: 10.1161/circresaha.116.308445
- Yang H, Biermann MH, Brauner JM, et al. New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation. Front Immunol. 2016;7. doi: 10.3389/fimmu.2016.00302
- Wang H, Li T, Chen S, et al. Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin. Arthritis Rheumatol. 2015;67(12):3190-200. doi: 10.1002/art.39296
- Чикина М.Н. Профилактика приступов артрита при назначении уратснижающей терапии у больных подагрой. Научно-практическая ревматология. 2018;56(6):760-6 [Chikina MN. Prevention of arthritis attacks in the use of urate-lowering therapy in patients with gout. Rheumatology Science and Practice. 2018;56(6):760-6 (in Russian)]. doi: 10.14412/1995-4484-2018-760-766
- Menegazzo L, Ciciliot S, Poncina N, et al. NETosis is induced by high glucose and associated with type 2 diabetes. Acta Diabetol. 2014;52(3):497-503. doi: 10.1007/s00592-014-0676-x
- Menegazzo L, Scattolini V, Cappellari R, et al. The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo. Acta Diabetol. 2018;55(6):593-601. doi: 10.1007/s00592-018-1129-8
- Bruderer SG, Bodmer M, Jick SS, Meier CR. Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study. Ann Rheum Dis. 2014;74(9):1651-8. doi: 10.1136/annrheumdis-2014-205337
- Шестаков А.В., Саприна Т.В., Ануфрак И.А., и др. Метформин: новые перспективы в химиопрофилактике и терапии рака. Российский биотерапевтический журнал. 2018;17(3):12-9 [Shestakov AV, Saprina TV, Anufrak IA, et al. Metformin: new perspectives in chemoprevention and therapy of cancer. Russian Journal of Biotherapy. 2018;17(3):12-9 (in Russian)]. doi: 10.17650/1726-9784-2018-17-3-12-19
- Барскова В.Г., Елисеев М.С., Кудаева Ф.М., и др. Влияние метформина на течение подагры и инсулинорезистентность. Клиническая медицина. 2009;87(7):41-6 [Barskova VG, Eliseev MS, Kudaeva FM, et al. Effect of metformine on the clinical course of gout and insulin resistance. Clinical Medicine. 2009;87(7):41-6 (in Russian)].
- Matsuura F, Yamashita S, Nakamura T, et al. Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: Visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity. Metabolism. 1998;47(8):929-33. doi: 10.1016/s0026-0495(98)90346-8
- Morales DR, Morris AD. Metformin in Cancer Treatment and Prevention. Ann Rev Med. 2015;66(1):17-29. doi: 10.1146/annurev-med-062613-093128
- Lawrence T. The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651. doi: 10.1101/cshperspect.a001651
- Hattori Y, Suzuki K, Hattori S, Kasai K. Metformin Inhibits Cytokine-Induced Nuclear Factor κB Activation Via AMP-Activated Protein Kinase Activation in Vascular Endothelial Cells. Hypertension. 2006;47(6):1183-8. doi: 10.1161/01.hyp.0000221429.94591.72
- Bijland S, Mancini SJ, Salt IP. Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin Sci. 2013;124(8):491-507. doi: 10.1042/cs20120536
- Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Nat Acad Sci U S A. 2012;110(3):972-7. doi: 10.1073/pnas.1221055110
- The Diabetes Prevention Program Research Group. Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance. Diabetes. 2005;54(5):1566-72. doi: 10.2337/diabetes.54.5.1566
- Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-41. doi: 10.1038/nature04516
- Jacques C, Gosset M, Berenbaum F, Gabay C. The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation. Vitam Horm. 2006;74:371-403. doi: 10.1016/S0083-6729(06)74016-X
- Joosten LA, Netea MG, Mylona E, et al. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum. 2010;62(11):3237-48.doi: 10.1002/art.27667
- Nishimura A, Akahoshi T, Takahashi M, et al. Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. J Leukoc Biol. 1997;62(4):444-9. doi: 10.1002/jlb.62.4.444
- Huang Z, Kraus VB. Does lipopolysaccharide-mediated inflammation have a role in OA? Nat Rev Rheumatol. 2016;12(2):123-9. doi: 10.1038/nrrheum.2015.158
- Collins KH, Paul HA, Reimer RA, et al. Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model. Osteoarthritis Cartilage. 2015;23(11):1989-98. doi: 10.1016/j.joca.2015.03.014
- Bramante C, Ingraham N, Murray T, et al. Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19. MedRxiv. 2020;2020.06.19.20135095. doi: 10.1101/2020.06.19.20135095
- Matsiukevich D, Piraino G, Lahni P, et al. Metformin ameliorates gender-and age-dependent hemodynamic instability and myocardial injury in murine hemorrhagic shock. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt. B):2680-91. doi: 10.1016/j.bbadis.2017.05.027
- Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-38. doi: 10.1038/nri.2016.90
- Son HJ, Lee J, Lee SY, et al. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediators Inflamm. 2014;2014:973986. doi: 10.1155/2014/973986
- Dai XJ, Tao JH, Fang X, et al. Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals. Inflammation. 2018;41(5):1955-64. doi: 10.1007/s10753-018-0839-y
- Shin N-R, Lee J-C, Lee H-Y, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2013;63(5):727-35. doi: 10.1136/gutjnl-2012-303839
- Lee H, Ko G. Effect of Metformin on Metabolic Improvement and Gut Microbiota. Appl Environ Microbiol. 2014;80(19):5935-43. doi: 10.1128/aem.01357-14
- Lee H, Lee Y, Kim J, et al. Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes. 2018;9(2):155-65. doi: 10.1080/19490976.2017.1405209
- Bauer PV, Duca FA, Waise TMZ, et al. Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway. Cell Metab. 2018;27(1):101-17.e5. doi: 10.1016/j.cmet.2017.09.019
- Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262-6. doi: 10.1038/nature15766
- De la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, et al. Metformin Is Associated With Higher Relative Abundance of Mucin-DegradingAkkermansia muciniphilaand Several Short-Chain Fatty Acid-Producing Microbiota in the Gut. Diabetes Care. 2016;40(1):54-62. doi: 10.2337/dc16-1324.