{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:47:55Z","timestamp":1757699275036,"version":"3.37.3"},"reference-count":68,"publisher":"Endocrinology Research Centre","issue":"3","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>Imeglimin is the first drug in a new class of tetrahydrotriazine-containing oral hypoglycemic agents called \u00abglimines\u00bb. Its\u00a0mechanism of action is aimed at achieving a double effect, firstly, to improve the function of beta cells of the pancreas, and secondly, to enhance the action of insulin in key tissues, including the liver and skeletal muscles. At the cellular level, imeglimin modulates mitochondrial function, which leads to an improvement in cellular energy metabolism, as well as to the protection of cells from death in conditions of excessive accumulation of reactive oxygen species. It is important to note that the mechanism of action of imeglimin differs from existing drugs used for the treatment of type 2 diabetes mellitus. Like glucagon-like peptide-1 receptor agonists, imeglimin enhances insulin secretion in an exclusively glucose-dependent manner, but their mechanism of action at the cellular level diverges. Sulfonylureas and glinides function by closing ATP-sensitive potassium channels to release insulin, which is also different from imeglimin. Compared with metformin, the effect of imeglimine is also significantly different. Other major classes of oral antihypertensive agents, such as sodium-glucose transporter-2 inhibitors, thiazolidinediones and \u03b1 glucosidase inhibitors mediate their action through mechanisms that do not overlap with imeglimine. Given such differences in the mechanisms of action, imeglimin can be used as part of combination therapy, for example with sitagliptin and metformin. The imeglimine molecule is well absorbed (Tmax-4), and the half-life is\u00a05\u20136 hours, is largely excreted through the kidneys, and also has no clinically significant interactions with either metformin or sitagliptin.<\/jats:p>","DOI":"10.14341\/probl12868","type":"journal-article","created":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T06:38:39Z","timestamp":1657953519000},"page":"57-66","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":2,"title":["Imeglimin: features of the mechanism of action and potential benefits"],"prefix":"10.14341","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2405-1801","authenticated-orcid":true,"given":"K. O.","family":"Kuznetsov","sequence":"first","affiliation":[{"name":"N.I. Pirogov Russian national research medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-7845","authenticated-orcid":true,"given":"A. A.","family":"Saetova","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5022-3470","authenticated-orcid":true,"given":"E. I.","family":"Mahmutova","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2351-949X","authenticated-orcid":true,"given":"A. G.","family":"Bobrik","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-2136","authenticated-orcid":true,"given":"D. V.","family":"Bobrik","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7844-8866","authenticated-orcid":true,"given":"I. R.","family":"Nagaev","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-5302","authenticated-orcid":true,"given":"A. D.","family":"Khamitova","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4079-201X","authenticated-orcid":true,"given":"A. M.","family":"Arapieva","sequence":"additional","affiliation":[{"name":"Bashkir state medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Pirags V, Lebovitz H, Fouqueray P. Imeglimin, a novel glimin oral antidiabetic, exhibits a good efficacy and safety profile in type 2 diabetic patients. Diabetes Obes Metab. 2012;14(9):852-858. doi: https:\/\/doi.org\/10.1111\/j.1463-1326.2012.01611.x","DOI":"10.1111\/j.1463-1326.2012.01611.x"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Fouqueray P, Pirags V, Diamant M, et al. The efficacy and safety of imeglimin as add-on therapy in patients with type 2 diabetes inadequately controlled with sitagliptin monotherapy. Diabetes Care. 2014;37(7):1924-1930. doi: https:\/\/doi.org\/10.2337\/dc13-2349","DOI":"10.2337\/dc13-2349"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Crabtree TS, DeFronzo RA, Ryder REJ, Bailey CJ. Imeglimin, a novel, first in-class, blood glucose-lowering agent: a systematic review and meta-analysis of clinical evidence. Br J Diabetes. 2020;20(1):28-31. doi: https:\/\/doi.org\/10.15277\/bjd.2020.247","DOI":"10.15277\/bjd.2020.247"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Yaribeygi H, Maleki M, Sathyapalan T, et al. Molecular Mechanisms by Which Imeglimin Improves Glucose Homeostasis. J Diabetes Res. 2020;2020:8768954. doi: https:\/\/doi.org\/10.1155\/2020\/8768954","DOI":"10.1155\/2020\/8768954"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Herder C, Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance. Eur J Clin Invest. 2011;41(6):679-692. doi: https:\/\/doi.org\/10.1111\/j.1365-2362.2010.02454.x","DOI":"10.1111\/j.1365-2362.2010.02454.x"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"DeFronzo RA, Simonson D, Ferrannini E. Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1982;23(4):313-319. doi: https:\/\/doi.org\/10.1007\/BF00253736","DOI":"10.1007\/BF00253736"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Ma ZA, Zhao Z, Turk J. Mitochondrial dysfunction and \u03b2-cell failure in type 2 diabetes mellitus. Exp Diabetes Res. 2012;2012:703538. doi: https:\/\/doi.org\/10.1155\/2012\/703538","DOI":"10.1155\/2012\/703538"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Haythorne E, Rohm M, van de Bunt M, et al. Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic \u03b2-cells. Nat Commun. 2019;10(1):2474. doi: https:\/\/doi.org\/10.1038\/s41467-019-10189-x","DOI":"10.1038\/s41467-019-10189-x"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Gonzalez-Franquesa A, Patti ME. Insulin Resistance and Mitochondrial Dysfunction. Adv Exp Med Biol. 2017;982:465-520. doi: https:\/\/doi.org\/10.1007\/978-3-319-55330-6_25","DOI":"10.1007\/978-3-319-55330-6_25"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133-2223. doi: https:\/\/doi.org\/10.1152\/physrev.00063.2017","DOI":"10.1152\/physrev.00063.2017"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Pinti MV, Fink GK, Hathaway QA, et al. Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis. Am J Physiol Endocrinol Metab. 2019;316(2):E268-E285. doi: https:\/\/doi.org\/10.1152\/ajpendo.00314.2018","DOI":"10.1152\/ajpendo.00314.2018"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133-2223. doi: https:\/\/doi.org\/10.1152\/physrev.00063.2017","DOI":"10.1152\/physrev.00063.2017"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Muoio DM. Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock. Cell. 2014;159(6):1253-1262. doi: https:\/\/doi.org\/10.1016\/j.cell.2014.11.034","DOI":"10.1016\/j.cell.2014.11.034"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Anderson EJ, Lustig ME, Boyle KE, et al. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest. 2009;119(3):573-581. doi: https:\/\/doi.org\/10.1172\/JCI37048","DOI":"10.1172\/JCI37048"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Katsyuba E, Romani M, Hofer D, Auwerx J. NAD+ homeostasis in health and disease. Nat Metab. 2020;2(1):9-31. doi: https:\/\/doi.org\/10.1038\/s42255-019-0161-5","DOI":"10.1038\/s42255-019-0161-5"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci. 2019;26(1):34. doi: https:\/\/doi.org\/10.1186\/s12929-019-0527-8","DOI":"10.1186\/s12929-019-0527-8"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Otonkoski T, Beattie GM, Mally MI, et al. Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells. J Clin Invest. 1993;92(3):1459-1466. doi: https:\/\/doi.org\/10.1172\/JCI116723","DOI":"10.1172\/JCI116723"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Clapham JC. Sixty Years of Drug Discovery for Type 2 Diabetes: Where Are We Now? Methods Mol Biol. 2020;2076:1-30. doi: https:\/\/doi.org\/10.1007\/978-1-4939-9882-1_1","DOI":"10.1007\/978-1-4939-9882-1_1"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Araki E, Haneda M, Kasuga M, et al. New glycemic targets for patients with diabetes from the Japan Diabetes Society. J Diabetes Investig. 2017;8(1):123-125. doi: https:\/\/doi.org\/10.1111\/jdi.12600","DOI":"10.1111\/jdi.12600"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Pacini G, Mari A, Fouqueray P, et al. Imeglimin increases glucosedependent insulin secretion and improves \u03b2-cell function in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17(6):541-545. doi: https:\/\/doi.org\/10.1111\/dom.12452","DOI":"10.1111\/dom.12452"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Fouqueray P, Leverve X, Fontaine E, et al. Imeglimin \u2010 a new oral anti\u2010diabetic that targets the three key defects of type 2 diabetes. J Diabetes Metab. 2011;2(4). doi: https:\/\/doi.org\/10.4172\/2155-6156.1000126","DOI":"10.4172\/2155-6156.1000126"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Hallakou\u2010Bozec S, Kergoat M, Moller DE, Bolze S. Imeglimin preserves islet \u03b2\u2010cell mass in Type 2 diabetic ZDF rats. Endocrinol Diabetes Metab. 2021;4(2). doi: https:\/\/doi.org\/10.1002\/edm2.193","DOI":"10.1002\/edm2.193"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Perry RJ, Cardone RL, Petersen MC, et al. Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in highfat-fed rodents. Am J Physiol Endocrinol Metab. 2016;311(2):461-470. doi: https:\/\/doi.org\/10.1152\/ajpendo.00009.2016","DOI":"10.1152\/ajpendo.00009.2016"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Vial G, Chauvin MA, Bendridi N, et al. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model. Diabetes. 2015;64(6):2254-2264. doi: https:\/\/doi.org\/10.2337\/db14-1220","DOI":"10.2337\/db14-1220"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Hallakou-Bozec S, Kergoat M, Fouqueray P, et al. Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action. PLoS One. 2021;16(2):e0241651. doi: https:\/\/doi.org\/10.1371\/journal.pone.0241651","DOI":"10.1371\/journal.pone.0241651"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Pick A, Clark J, Kubstrup C, et al. Role of apoptosis in failure of betacell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat. Diabetes. 1998;47(3):358-364. doi: https:\/\/doi.org\/10.2337\/diabetes.47.3.358","DOI":"10.2337\/diabetes.47.3.358"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402-2410. doi: https:\/\/doi.org\/10.1210\/jcem.85.7.6661","DOI":"10.1210\/jcem.85.7.6661"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Hallakou-Bozec S, Vial G, Kergoat M, et al. Mechanism of action of Imeglimin: A novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab. 2021;23(3):664-673. doi: https:\/\/doi.org\/10.1111\/dom.14277","DOI":"10.1111\/dom.14277"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Stumvoll M, Van Haeften T, Fritsche A, Gerich J. Oral glucose tolerance test indexes for insulin sensitivity and secretion based on various availabilities of sampling times. Diabetes Care. 2001;24(4):796-797. doi: https:\/\/doi.org\/10.2337\/diacare.24.4.796","DOI":"10.2337\/diacare.24.4.796"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Vial G, Dubouchaud H, Leverve XM. Liver mitochondria and insulin resistance. Acta Biochim Pol. 2010;57(4):389-492. doi: https:\/\/doi.org\/10.18388\/abp.2010_2422","DOI":"10.18388\/abp.2010_2422"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Cant\u00f3 C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. doi: https:\/\/doi.org\/10.1016\/j.cmet.2015.05.023","DOI":"10.1016\/j.cmet.2015.05.023"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Detaille D, Vial G, Borel AL, et al. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Cell Death Discov. 2016;2:15072. doi: https:\/\/doi.org\/10.1038\/cddiscovery.2015.72","DOI":"10.1038\/cddiscovery.2015.72"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305(5684):626-629. doi: https:\/\/doi.org\/10.1126\/science.1099320","DOI":"10.1126\/science.1099320"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Javadov S, Karmazyn M. Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell Physiol Biochem. 2007;20(1-4):1-22. doi: https:\/\/doi.org\/10.1159\/000103747","DOI":"10.1159\/000103747"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Sliwinska A, Drzewoski J. Molecular action of metformin in hepatocytes: an updated insight. Curr Diabetes Rev. 2015;11(3):175-181. doi: https:\/\/doi.org\/10.2174\/1573399811666150325233108","DOI":"10.2174\/1573399811666150325233108"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Vial G, Lamarche F, Cottet-Rousselle C, et al. The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells. Endocrinol Diabetes Metab. 2021;4(2):e00211. doi: https:\/\/doi.org\/10.1002\/edm2.211","DOI":"10.1002\/edm2.211"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Dell\u2019Aglio DM, Perino LJ, Kazzi Z, et al. Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Ann Emerg Med. 2009;54(6):818-823. doi: https:\/\/doi.org\/10.1016\/j.annemergmed.2009.04.023","DOI":"10.1016\/j.annemergmed.2009.04.023"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. doi: https:\/\/doi.org\/10.1016\/j.metabol.2015.10.014","DOI":"10.1016\/j.metabol.2015.10.014"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Madiraju AK, Erion DM, Rahimi Y, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014;510(7506):542-546. doi: https:\/\/doi.org\/10.1038\/nature13270","DOI":"10.1038\/nature13270"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Katsyuba E, Mottis A, Zietak M, et al. De novo NAD+ synthesis enhances mitochondrial function and improves health. Nature. 2018;563(7731):354-359. doi: https:\/\/doi.org\/10.1038\/s41586-018-0645-6","DOI":"10.1038\/s41586-018-0645-6"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Kato I, Takasawa S, Akabane A, et al. Regulatory role of CD38 (ADPribosyl cyclase\/cyclic ADP-ribose hydrolase) in insulin secretion by glucose in pancreatic beta cells. Enhanced insulin secretion in CD38- expressing transgenic mice. J Biol Chem. 1995;270(50):30045-30050. doi: https:\/\/doi.org\/10.1074\/jbc.270.50.30045","DOI":"10.1074\/jbc.270.50.30045"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Takasawa S, Nata K, Yonekura H, Okamoto H. Cyclic ADP-ribose in insulin secretion from pancreatic beta cells. Science. 1993;259(5093):370-373. doi: https:\/\/doi.org\/10.1126\/science.8420005","DOI":"10.1126\/science.8420005"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Campbell JE, Newgard CB. Mechanisms controlling pancreatic islet cell function in insulin secretion. Nat Rev Mol Cell Biol. 2021;22(2):142-158. doi: https:\/\/doi.org\/10.1038\/s41580-020-00317-7","DOI":"10.1038\/s41580-020-00317-7"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Proks P, Reimann F, Green N, Gribble F, Ashcroft F. Sulfonylurea stimulation of insulin secretion. Diabetes. 2002;51(3):368-376. doi: https:\/\/doi.org\/10.2337\/diabetes.51.2007.s368","DOI":"10.2337\/diabetes.51.2007.S368"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Kuefner MS. Secretory Phospholipase A2s in Insulin Resistance and Metabolism. Front Endocrinol (Lausanne). 2021;12:732726. doi: https:\/\/doi.org\/10.3389\/fendo.2021.732726","DOI":"10.3389\/fendo.2021.732726"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Jensen MV, Joseph JW, Ronnebaum SM, et al. Metabolic cycling in control of glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab. 2008;295(6):1287-1297. doi: https:\/\/doi.org\/10.1152\/ajpendo.90604.2008","DOI":"10.1152\/ajpendo.90604.2008"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Takeuchi M, Yamamoto T. Apoptosis induced by NAD depletion is inhibited by KN-93 in a CaMKII-independent manner. Exp Cell Res. 2015;335(1):62-67. doi: https:\/\/doi.org\/10.1016\/j.yexcr.2015.05.019","DOI":"10.1016\/j.yexcr.2015.05.019"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Pittelli M, Felici R, Pitozzi V, et al. Pharmacological effects of exogenous NAD on mitochondrial bioenergetics, DNA repair, and apoptosis. Mol Pharmacol. 2011;80(6):1136-1146. doi: https:\/\/doi.org\/10.1124\/mol.111.073916","DOI":"10.1124\/mol.111.073916"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Lachaux M, Souli\u00e9 M, Hamzaoui M, et al. Short-and long-term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome. Endocrinol Diabetes Metab. 2020;3(3):e00128. doi: https:\/\/doi.org\/10.1002\/edm2.128","DOI":"10.1002\/edm2.128"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Dubourg J, Perrimond-Dauchy S, Felices M, et al. Absence of QTc prolongation in a thorough QT study with imeglimin, a first in class oral agent for type 2 diabetes mellitus. Eur J Clin Pharmacol. 2020;76(10):1393-1400. doi: https:\/\/doi.org\/10.1007\/s00228-020-02929-6","DOI":"10.1007\/s00228-020-02929-6"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Cl\u00e9mence C, Fouqueray P, S\u00e9bastien B. In Vitro Investigation, Pharmacokinetics, and Disposition of Imeglimin, a Novel Oral Antidiabetic Drug, in Preclinical Species and Humans. Drug Metab Dispos. 2020;48(12):1330-1346. doi: https:\/\/doi.org\/10.1124\/dmd.120.000154","DOI":"10.1124\/dmd.120.000154"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577-1585. doi: https:\/\/doi.org\/10.1007\/s00125-017-4342-z","DOI":"10.1007\/s00125-017-4342-z"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Marchetti P, Del Guerra S, Marselli L, et al. Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab. 2004;89(11):5535-5541. doi: https:\/\/doi.org\/10.1210\/jc.2004-0150","DOI":"10.1210\/jc.2004-0150"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Lablanche S, Cottet-Rousselle C, Lamarche F, et al. Protection of pancreatic INS-1 \u03b2-cells from glucose- and fructoseinduced cell death by inhibiting mitochondrial permeability transition with cyclosporin A or metformin. Cell Death Dis. 2011;2(3):e134. doi: https:\/\/doi.org\/10.1038\/cddis.2011.15","DOI":"10.1038\/cddis.2011.15"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Vial G, Detaille D, Guigas B. Role of Mitochondria in the Mechanism(s) of Action of Metformin. Front Endocrinol (Lausanne). 2019;10:294. doi: https:\/\/doi.org\/10.3389\/fendo.2019.00294","DOI":"10.3389\/fendo.2019.00294"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"McKiney JM, Irwin N, Flatt PR, et al. Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal \u03b2-cells. Biol Chem. 2010;391(12):1451-1459. doi: https:\/\/doi.org\/10.1515\/BC.2010.139","DOI":"10.1515\/bc.2010.139"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"Fouqueray P, Pirags V, Inzucchi SE, et al. The efficacy and safety of imeglimin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Diabetes Care. 2013;36(3):565-568. doi: https:\/\/doi.org\/10.2337\/dc12-0453","DOI":"10.2337\/dc12-0453"},{"key":"ref58","unstructured":"Prophylaxis of diabetes mellitus type 2: the role and place of Metformin. Endokrinologiya: Novosti. Mneniya. Obuchenie. 2017;18(1):78-87. (In Russ.)."},{"key":"ref59","unstructured":"US Food and Drug Administration. Glimeperide Product Label Volume 2020, 2016."},{"key":"ref60","unstructured":"US Food and Drug Administration. Jardiance (Empagliflozin) Product Label Volume 2020, 2014."},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"Idris I, Donnelly R. Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug. Diabetes Obes Metab. 2009;11(2):79-88. doi: https:\/\/doi.org\/10.1111\/j.1463-1326.2008.00982.x","DOI":"10.1111\/j.1463-1326.2008.00982.x"},{"key":"ref62","unstructured":"US Food and Drug Administration. Acarbose Product Label; 2020, 2011."},{"key":"ref63","doi-asserted-by":"crossref","unstructured":"Derosa G, Maffioli P. Efficacy and safety profile evaluation of acarbose alone and in association with other antidiabetic drugs: a systematic review. Clin Ther. 2012;34(6):1221-1236. doi: https:\/\/doi.org\/10.1016\/j.clinthera.2012.04.012","DOI":"10.1016\/j.clinthera.2012.04.012"},{"key":"ref64","unstructured":"US Food and Drug Administration. Dulaglutide Product Label; 2020, 2017."},{"key":"ref65","unstructured":"US Food and Drug Administration. Actos (Pioglitazone Hydrochloride) Product Label; 2020, 1999."},{"key":"ref66","doi-asserted-by":"crossref","unstructured":"Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35(6):992-1019. doi: https:\/\/doi.org\/10.1210\/er.2014-1035","DOI":"10.1210\/er.2014-1035"},{"key":"ref67","unstructured":"US Food and Drug Administration. Actos (Pioglitazone Hydrochloride) Product Label; 2020, 1999."},{"key":"ref68","doi-asserted-by":"crossref","unstructured":"Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med. 2002;53:409-435. doi: https:\/\/doi.org\/10.1146\/annurev.med.53.082901.104018.","DOI":"10.1146\/annurev.med.53.082901.104018"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/12868\/10277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T06:39:44Z","timestamp":1657953584000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/12868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,11]]},"references-count":68,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,7,15]]}},"URL":"https:\/\/doi.org\/10.14341\/probl12868","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"type":"electronic","value":"2308-1430"},{"type":"print","value":"0375-9660"}],"subject":[],"published":{"date-parts":[[2022,3,11]]}}}