Preview

Медицинский Совет

Расширенный поиск

Метформин при предиабете: ключевые механизмы профилактики диабета и кардиометаболических рисков

https://doi.org/10.21518/2079-701X-2022-16-10-96-103

Аннотация

Сегодня мировым медицинским сообществом предиабет рассматривается как ранний сахарный диабет. Накопленные научные данные свидетельствуют о том, что предиабет характеризуется спектром осложнений, аналогичных при сахарном диабете, т. е. ухудшение сердечно-сосудистого прогноза начинается уже на стадии предиабета. В текущий период времени метформин фактически является единственным препаратом, широко назначаемым для лечения предиабета с целью профилактики сахарного диабета 2-го типа и сердечно-сосудистых заболеваний, ассоциированных с инсулинорезистентностью и гиперинсулинемией. Между тем метаболически нездоровое ожирение, характеризующееся гиперинсулинемией и инсулинорезистентностью, ассоциировано со значительно более неблагоприятным течением предиабета и с самым высоким риском развития как сахарного диабета 2-го типа, так и сердечно-сосудистых заболеваний, развития/прогрессии хронической болезни почек. Приоритетность метформина для коррекции наиболее прогностически неблагоприятных фенотипов предиабета – тема настоящего обзора, который также посвящен описанию наиболее значимых механизмов, обеспечивающих те эффекты метформина, которые лежат в основе коррекции ключевых нарушений, детерминирующих неблагоприятный прогноз предиабета. В частности, обозначена роль нездорового питания, его эффектов на развитие дисбаланса в составе микробиоты желудочно-кишечного тракта, который, в свою очередь, влечет за собой каскад метаболических нарушений, лежащих в основе формирования метаболического нездоровья. Обозначена ключевая роль метформина как препарата, защищающего от развития этих нарушений. Представленные в обзоре данные будут полезны для персонификации выбора как объема вмешательств, так и их характера у пациентов с разными фенотипическими характеристиками.

Об авторе

А. Ю. Бабенко
Национальный медицинский исследовательский центр имени В.А. Алмазова
Россия

Бабенко Алина Юрьевна, доктор медицинских наук, руководитель научно-исследовательского отдела генетических рисков и персонифицированной профилактики, заведующий научно-исследовательской лабораторией предиабета и метаболических нарушений Научного центра мирового уровня «Центр персонализированной медицины», заведующий научно-исследовательской лабораторией диабетологии, профессор кафедры внутренних болезней Института медицинского образования

197341, Санкт-Петербург, ул. Аккуратова, д. 2



Список литературы

1. Lakka H.M., Laaksonen D.E., Lakka T.A., Niskanen L.K., Kumpusalo E., Tuomilehto J., Salonen J.T. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288(21):2709–2716. https://doi.org/10.1001/jama.288.21.2709.

2. Thomas M.C., Cooper M.E., Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2016;12(2):73–81. https://doi.org/10.1038/nrneph.2015.173.

3. Einarson T.R., Acs A., Ludwig C., Panton U.H. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol. 2018;17(1):83. https://doi.org/10.1186/s12933-018-0728-6.

4. Nichols G.A., Gullion C.M., Koro C.E., Ephross S.A., Brown J.B. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004;27(8):1879–1784. https://doi.org/10.2337/diacare.27.8.1879.

5. Ndumele C.E., Matsushita K., Lazo M., Bello N., Blumenthal R.S., Gerstenblith G. et al. Obesity and Subtypes of Incident Cardiovascular Disease. J Am Heart Assoc. 2016;5(8):e003921. https://doi.org/10.1161/JAHA.116.003921.

6. Jenkins D.J.A., Dehghan M., Mente A., Bangdiwala S.I., Rangarajan S., Srichaikul K. et al. Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality. N Engl J Med. 2021;384(14):1312–1322. https://doi.org/10.1056/NEJMoa2007123.

7. Leow M.K., Henry C.J. Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality. N Engl J Med. 2021;385(4):378. https://doi.org/10.1056/NEJMc2107926.

8. Kirkpatrick C.F., Maki K.C. Dietary Influences on Atherosclerotic Cardiovascular Disease Risk. Curr Atheroscler Rep. 2021;23(10):62. https://doi.org/10.1007/s11883-021-00954-z.

9. Morigny P., Boucher J., Arner P., Langin D. Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics. Nat Rev Endocrinol. 2021;17(5):276–295. https://doi.org/10.1038/s41574-021-00471-8.

10. Stenkula K.G., Erlanson-Albertsson C. Adipose cell size: importance in health and disease. Am J Physiol Regul Integr Comp Physiol. 2018;315(2):R284–R295. https://doi.org/10.1152/ajpregu.00257.2017.

11. Ahlqvist E., Storm P., Käräjämäki A., Martinell M., Dorkhan M., Carlsson A. et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018;6(5):361–369. https://doi.org/10.1016/S2213-8587(18)30051-2.

12. Häring H.U. Novel phenotypes of prediabetes? Diabetologia. 2016;59(9):1806–1818. https://doi.org/10.1007/s00125-016-4015-3.

13. Stefan N., Fritsche A., Schick F., Häring H.U. Phenotypes of prediabetes and stratification of cardiometabolic risk. Lancet Diabetes Endocrinol. 2016;4(9):789–798. https://doi.org/10.1016/S2213-8587(16)00082-6.

14. Stefan N., Staiger H., Wagner R., Machann J., Schick F., Häring H.U., Fritsche A. A high-risk phenotype associates with reduced improvement in glycaemia during a lifestyle intervention in prediabetes. Diabetologia. 2015;58(12):2877–2884. https://doi.org/10.1007/s00125-015-3760-z.

15. Wagner R., Heni M., Tabák A.G., Machann J., Schick F., Randrianarisoa E. et al. Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes. Nat Med. 2021;27(1):49–57. https://doi.org/10.1038/s41591-020-1116-9.

16. Hur K.Y., Lee M.S. New mechanisms of metformin action: Focusing on mitochondria and the gut. J Diabetes Investig. 2015;6(6):600–609. https://doi.org/10.1111/jdi.12328.

17. Van Son J., Koekkoek L.L., La Fleur S.E., Serlie M.J., Nieuwdorp M. The Role of the Gut Microbiota in the Gut-Brain Axis in Obesity: Mechanisms and Future Implications. Int J Mol Sci. 2021;22(6):2993. https://doi.org/10.3390/ijms22062993.

18. Rastelli M., Knauf C., Cani P.D. Gut Microbes and Health: A Focus on the Mechanisms Linking Microbes, Obesity, and Related Disorders. Obesity (Silver Spring). 2018;26(5):792–800. https://doi.org/10.1002/oby.22175.

19. Belkaid Y., Harrison O.J. Homeostatic Immunity and the Microbiota. Immunity. 2017;46(4):562–576. https://doi.org/10.1016/j.immuni.2017.04.008.

20. Hersoug L.G., Møller P., Loft S. Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue: implications for inflammation and obesity. Obes Rev. 2016;17(4):297–312. https://doi.org/10.1111/obr.12370.

21. Postler T.S., Ghosh S. Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System. Cell Metab. 2017;26(1):110–130. https://doi.org/10.1016/j.cmet.2017.05.008.

22. Møller C.L., Vistisen D., Færch K., Johansen N.B., Witte D.R., Jonsson A. et al. Glucose-Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITION-PRO Study. J Clin Endocrinol Metab. 2016;101(2):485–493. https://doi.org/10.1210/jc.2015-3133.

23. Meijles D.N., Zoumpoulidou G., Markou T., Rostron K.A., Patel R., Lay K. et al. The cardiomyocyte “redox rheostat”: Redox signalling via the AMPKmTOR axis and regulation of gene and protein expression balancing vival and death. J Mol Cell Cardiol. 2019;129:118–129. https://doi.org/10.1016/j.yjmcc.2019.02.006.

24. Krzysiak T.C., Thomas L., Choi Y.J., Auclair S., Qian Y., Luan S. et al. An Insulin-Responsive Sensor in the SIRT1 Disordered Region Binds DBC1 and PACS-2 to Control Enzyme Activity. Mol Cell. 2018;72(6):985– 998.e7. https://doi.org/10.1016/j.molcel.2018.10.007.

25. Paula-Gomes S., Gonçalves D.A., Baviera A.M., Zanon N.M., Navegantes L.C., Kettelhut I.C. Insulin suppresses atrophyand autophagy-related genes in heart tissue and cardiomyocytes through AKT/FOXO signaling. Horm Metab Res. 2013;45(12):849–855. https://doi.org/10.1055/s-0033-1347209.

26. Baek J.H., Jin S.M., Bae J.C., Jee J.H., Yu T.Y., Kim S.K. et al. Serum Calcium and the Risk of Incident Metabolic Syndrome: A 4.3-Year Retrospective Longitudinal Study. Diabetes Metab J. 2017;41(1):60–68. https://doi.org/10.4093/dmj.2017.41.1.60.

27. Stepensky D., Friedman M., Raz I., Hoffman A. Pharmacokineticpharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab Dispos. 2002;30(8):861–868. https://doi.org/10.1124/dmd.30.8.861.

28. Bailey C.J., Mynett K.J., Page T. Importance of the intestine as a site of metformin-stimulated glucose utilization. Br J Pharmacol. 1994;112(2):671–675. https://doi.org/10.1111/j.1476-5381.1994.tb13128.x.

29. Bailey C.J., Wilcock C., Scarpello J.H. Metformin and the intestine. Diabetologia. 2008;51(8):1552–1553. https://doi.org/10.1007/s00125-008-1053-5.

30. Tucker G.T., Casey C., Phillips P.J., Connor H., Ward J.D., Woods H.F. Metformin kinetics in healthy subjects and in patients with diabetes mellitus. Br J Clin Pharmacol. 1981;12(2):235–246. https://doi.org/10.1111/j.1365-2125.1981.tb01206.x.

31. Gorboulev V., Schürmann A., Vallon V., Kipp H., Jaschke A., Klessen D. et al. Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes. 2012;61(1):187–196. https://doi.org/10.2337/db11-1029.

32. Kuhre R.E., Frost C.R., Svendsen B., Holst J.J. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine. Diabetes. 2015;64(2):370–382. https://doi.org/10.2337/db14-0807.

33. Parker H.E., Adriaenssens A., Rogers G., Richards P., Koepsell H., Reimann F., Gribble F.M. Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia. 2012;55(9): 2445–2455. https://doi.org/10.1007/s00125-012-2585-2.

34. Bauer P.V., Duca F.A., Waise T.M.Z., Rasmussen B.A., Abraham M.A., Dranse H.J. et al. Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway. Cell Metab. 2018;27(1):101–117.e5. https://doi.org/10.1016/j.cmet.2017.09.019.

35. Sun L., Xie C., Wang G., Wu Y., Wu Q., Wang X. et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018;24(12):1919–1929. https://doi.org/10.1038/s41591-018-0222-4.

36. Lee C.B., Chae S.U., Jo S.J., Jerng U.M., Bae S.K. The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus. Int J Mol Sci. 2021;22(7):3566. https://doi.org/10.3390/ijms22073566.

37. Den Besten G., van Eunen K., Groen A.K., Venema K., Reijngoud D.J., Bakker B.M. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325–2340. https://doi.org/10.1194/jlr.R036012.

38. Lee H., Lee Y., Kim J., An J., Lee S., Kong H. et al. Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes. 2018;9(2):155–165. https://doi.org/10.1080/19490976.2017.1405209.

39. Rios-Covian D., Arboleya S., Hernandez-Barranco A.M., Alvarez-Buylla J.R., Ruas-Madiedo P., Gueimonde M., de los Reyes-Gavilan C.G. Interactions between Bifidobacterium and Bacteroides species in cofermentations are affected by carbon sources, including exopolysaccharides produced by bifidobacteria. Appl Environ Microbiol. 2013;79(23):7518–7524. https://doi.org/10.1128/AEM.02545-13.

40. Ryan P.M., Patterson E., Carafa I., Mandal R., Wishart D.S., Dinan T.G. et al. Metformin and Dipeptidyl Peptidase-4 Inhibitor Differentially Modulate the Intestinal Microbiota and Plasma Metabolome of Metabolically Dysfunctional Mice. Can J Diabetes. 2020;44(2):146–155.e2. https://doi.org/10.1016/j.jcjd.2019.05.008.

41. Zhang W., Xu J.H., Yu T., Chen Q.K. Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice. Biomed Pharmacother. 2019;118:109131. https://doi.org/10.1016/j.biopha.2019.109131.

42. Li X., Wang E., Yin B., Fang D., Chen P., Wang G. et al. Effects of Lactobacillus casei CCFM419 on insulin resistance and gut microbiota in type 2 diabetic mice. Benef Microbes. 2017;8(3):421–432. https://doi.org/10.3920/BM2016.0167.

43. Zheng J., Li H., Zhang X., Jiang M., Luo C., Lu Z. et al. Prebiotic Mannan-Oligosaccharides Augment the Hypoglycemic Effects of Metformin in Correlation with Modulating Gut Microbiota. J Agric Food Chem. 2018;66(23):5821–5831. https://doi.org/10.1021/acs.jafc.8b00829.

44. Shin N.R., Lee J.C., Lee H.Y., Kim M.S., Whon T.W., Lee M.S., Bae J.W. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727–735. https://doi.org/10.1136/gutjnl-2012-303839.

45. Wu H., Esteve E., Tremaroli V., Khan M.T., Caesar R., Mannerås-Holm L. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017;23(7):850–858. https://doi.org/10.1038/nm.4345.

46. Lee H., Ko G. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol. 2014;80(19):5935–5943. https://doi.org/10.1128/AEM.01357-14.

47. Gao Z., Yin J., Zhang J., Ward R.E., Martin R.J., Lefevre M. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58(7):1509–1517. https://doi.org/10.2337/db08-1637.

48. Lin H.V., Frassetto A., Kowalik E.J. Jr, Nawrocki A.R., Lu M.M., Kosinski J.R. et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE. 2012;7(4):e35240. https://doi.org/10.1371/journal.pone.0035240.

49. Lynn F.C., Thompson S.A., Pospisilik J.A., Ehses J.A., Hinke S.A., Pamir N. et al. A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. FASEB J. 2003;17(1):91–93. https://doi.org/10.1096/fj.02-0243fje.

50. Ahmadi S., Razazan A., Nagpal R., Jain S., Wang B., Mishra S.P. et al. Metformin Reduces Aging-Related Leaky Gut and Improves Cognitive Function by Beneficially Modulating Gut Microbiome/Goblet Cell/Mucin Axis. J Gerontol A Biol Sci Med Sci. 2020;75(7):e9–e21. https://doi.org/10.1093/gerona/glaa056.

51. Liu Y., Wang C., Li J., Li T., Zhang Y., Liang Y., Mei Y. Phellinus linteus polysaccharide extract improves insulin resistance by regulating gut microbiota composition. FASEB J. 2020;34(1):1065–1078. https://doi.org/10.1096/fj.201901943RR.

52. Pryor R., Norvaisas P., Marinos G., Best L., Thingholm L.B., Quintaneiro L.M. et al. Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. Cell. 2019;178(6):1299–1312.e29. https://doi.org/10.1016/j.cell.2019.08.003.

53. Cui H.X., Zhang L.S., Luo Y., Yuan K., Huang Z.Y., Guo Y. A Purified Anthraquinone-Glycoside Preparation From Rhubarb Ameliorates Type 2 Diabetes Mellitus by Modulating the Gut Microbiota and Reducing Inflammation. Front Microbiol. 2019;10:1423. https://doi.org/10.3389/fmicb.2019.01423.

54. Vrieze A., Van Nood E., Holleman F., Salojärvi J., Kootte R.S., Bartelsman J.F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–916.e7. https://doi.org/10.1053/j.gastro.2012.06.031.

55. Delzenne N.M., Cani P.D., Everard A., Neyrinck A.M., Bindels L.B. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia. 2015;58(10):2206–2217. https://doi.org/10.1007/s00125-015-3712-7.

56. Balakumar M., Prabhu D., Sathishkumar C., Prabu P., Rokana N., Kumar R. et al. Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice. Eur J Nutr. 2018;57(1):279–295. https://doi.org/10.1007/s00394-016-1317-7.

57. Carvalho B.M., Guadagnini D., Tsukumo D.M.L., Schenka A.A., Latuf-Filho P., Vassallo J. et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia. 2012;55(10):2823–2834. https://doi.org/10.1007/s00125-012-2648-4.

58. Turnbaugh P.J., Hamady M., Yatsunenko T., Cantarel B.L., Duncan A., Ley R.E. et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–484. https://doi.org/10.1038/nature07540.

59. Ma W., Chen J., Meng Y., Yang J., Cui Q., Zhou Y. Metformin Alters Gut Microbiota of Healthy Mice: Implication for Its Potential Role in Gut Microbiota Homeostasis. Front Microbiol. 2018;9:1336. https://doi.org/10.3389/fmicb.2018.01336.

60. Rosario D., Benfeitas R., Bidkhori G., Zhang C., Uhlen M., Shoaie S., Mardinoglu A. Understanding the Representative Gut Microbiota Dysbiosis in Metformin-Treated Type 2 Diabetes Patients Using Genome-Scale Metabolic Modeling. Front Physiol. 2018;9:775. https://doi.org/10.3389/fphys.2018.00775.

61. Depommier C., Everard A., Druart C., Plovier H., Van Hul M., Vieira-Silva S. et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25(7):1096–1103. https://doi.org/10.1038/s41591-019-0495-2.

62. Napolitano A., Miller S., Nicholls A.W., Baker D., Van Horn S., Thomas E. et al. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS ONE. 2014;9(7):e100778. https://doi.org/10.1371/journal.pone.0100778.

63. De la Cuesta-Zuluaga J., Mueller N.T., Corrales-Agudelo V., VelásquezMejía E.P., Carmona J.A., Abad J.M., Escobar J.S. Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut. Diabetes Care. 2017;40(1):54–62. https://doi.org/10.2337/dc16-1324.

64. Elbere I., Kalnina I., Silamikelis I., Konrade I., Zaharenko L., Sekace K. et al. Association of metformin administration with gut microbiome dysbiosis in healthy volunteers. PLoS ONE. 2018;13(9):e0204317. https://doi.org/10.1371/journal.pone.0204317.

65. Li T., Chiang J.Y. Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev. 2014;66(4):948–983. https://doi.org/10.1124/pr.113.008201.

66. Sansome D.J., Xie C., Veedfald S., Horowitz M., Rayner C.K., Wu T. Mechanism of glucose-lowering by metformin in type 2 diabetes: Role of bile acids. Diabetes Obes Metab. 2020;22(2):141–148. https://doi.org/10.1111/dom.13869.

67. Scarpello J.H., Hodgson E., Howlett H.C. Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabet Med. 1998;15(8):651–656. https://doi.org/10.1002/(SICI)1096-9136(199808)15:8<651::AID-DIA628>3.0.CO;2-A.

68. Meng X.M., Ma X.X., Tian Y.L., Jiang Q., Wang L.L., Shi R. et al. Metformin improves the glucose and lipid metabolism via influencing the level of serum total bile acids in rats with streptozotocin-induced type 2 diabetes mellitus. Eur Rev Med Pharmacol Sci. 2017;21(9):2232–2237. Available at: https://www.europeanreview.org/article/12704.

69. Brønden A., Albér A., Rohde U., Rehfeld J.F., Holst J.J., Vilsbøll T., Knop F.K. Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2017;102(11):4153–4162. https://doi.org/10.1210/jc.2017-01091.

70. Forslund K., Hildebrand F., Nielsen T., Falony G., Le Chatelier E., Sunagawa S. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262–266. https://doi.org/10.1038/nature15766.

71. Breit S.N., Brown D.A., Tsai V.W. The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe? Annu Rev Physiol. 2021;83:127–151. https://doi.org/10.1146/annurev-physiol-022020-045449.

72. Gerstein H.C., Pare G., Hess S., Ford R.J., Sjaarda J., Raman K. et al. Growth Differentiation Factor 15 as a Novel Biomarker for Metformin. Diabetes Care. 2017;40(2):280–283. https://doi.org/10.2337/dc16-1682.

73. Natali A., Nesti L., Venturi E., Shore A.C., Khan F., Gooding K. et al. Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes: A nested, case-control study. Diabetes Obes Metab. 2019;21(2):412–416. https://doi.org/10.1111/dom.13519.

74. Preiss D., Lloyd S.M., Ford I., McMurray J.J., Holman R.R., Welsh P. et al. Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. Lancet Diabetes Endocrinol. 2014;2(2):116–124. https://doi.org/10.1016/S2213-8587(13)70152-9.

75. Coll A.P., Chen M., Taskar P., Rimmington D., Patel S., Tadross J.A. et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature. 2020;578(7795):444–448. https://doi.org/10.1038/s41586-019-1911-y.

76. Blonde L., Dailey G.E., Jabbour S.A., Reasner C.A., Mills D.J. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Curr Med Res Opin. 2004;20(4):565–572. https://doi.org/10.1185/030079904125003278.

77. Аметов А.С., Барыкина И.Н., Бондарь И.А., Вайсберг А.Р., Вербовая Н.И., Жукова Л.А. и др. Приверженность пациентов терапии метформином пролонгированного действия (Глюкофаж® Лонг) в условиях реальной клинической практики в Российской Федерации. Эндокринология: новости, мнения, обучение. 2017;(4):52–63. https://doi.org/10.24411/2304-9529-2017-00054.


Рецензия

Для цитирования:


Бабенко А.Ю. Метформин при предиабете: ключевые механизмы профилактики диабета и кардиометаболических рисков. Медицинский Совет. 2022;(10):96-103. https://doi.org/10.21518/2079-701X-2022-16-10-96-103

For citation:


Babenko A.Yu. Metformin in prediabetes: key mechanisms for the prevention of diabetes and cardiometabolic risks. Meditsinskiy sovet = Medical Council. 2022;(10):96-103. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-10-96-103

Просмотров: 338


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)