Cardiovascular protective effects of metformin

Abstract

Abstract: Metformin belongs to biguanide drugs, used as oral hypoglycemic agents in type 2 diabetes (T2DM) for 50 years, and its anti-hyperglycemic effect has been recognized. Furthermore, in recent years more and more studies found that metformin has additional cardiovascular protective effects, including the inhibition of atherosclerosis (AS), heart failure and myocardial infarction. However, the specific effect of metformin on cardiovascular protection is still unclear. This article reviews the effect of metformin in cardiovascular disease and discusses its possible mechanisms.

Key words: Metformin, Atherosclerosis, Heart failure, Myocardial infarction

CLC Number:

R977.15

FANG Li-juan, LIU Nai-feng. Cardiovascular protective effects of metformin[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(2): 232-236.

References

[1] Ong CR, Molyneaux LM, Constanino MI, et al. Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes[J]. Diabetes Care, 2006,29(11):2361-2364.
[2] American Diabetes Association. Standards of medical care in diabetes[J]. Diabetes Care, 2008, 31(Suppl 1): S12-S54.
[3] UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS33) [J]. Lancet, 1998, 352(9178):837-853.
[4] Mamputu JC, Wiernsperger N, Renier G. Metformin inhibits monocyte adhesion to endothelial cells and foam cell formation: potential implications for diabetic vascular diseases[J]. Br J Diabetes Vasc Dis, 2003, 3(4): 302-310.
[5] Ling Li, Jean-Claude Mamputu, Nicolas Wiernsperger, et al. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin[J]. Diabetes, 2005,54(7):2227-2234.
[6] Wiernsperger NF. Metformin: intrinsic vasculoprotective properties[J]. Diabetes Technol Therap, 2000, 2(2): 259-272.
[7] Mamputu JC, Wiernsperger NF, Renier G. Antiatherogenic properties of metformin: the experimental evidence [J]. Diabetes Metab, 2003,29(4):6S71-6S76
[8] Weichert W, Breddin HK. Antithrombotic effects of metformin in laser injured arteries[J]. Diabetes Metab, 1988, 14(4):540-543.
[9] He G, Pedersen SB, Bruun JM, et al. Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro[J]. Horm Metab Res, 2003,35(1):18-23.
[10]Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus[J]. J Am Coll Cardiol, 2001,37(5):1344-1350.
[11]Orio F, Palomba S, Cascella T, et al. Improvement in endothelial structure and function after metformin treatment in young normal weight women with polycystic ovary syndrome: results of a 6-month study[J]. J Clin Endocrinol Metab, 2005,90(11):6072-6076.
[12]陈碧莲, 刘慧霞, 潘瑞喆. 葡萄糖耐量减低患者二甲双胍干预治疗的临床效果[J].中国临床药理学与治疗学, 2007, 12 (1): 107-110.
[13]Eurich DT, McAlister FA, Blackburn DF, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review[J]. BMJ, 2007, 335(7618): 497-501.
[14]Hideyuki Sasaki, Hiroshi Asanuma, Masashi Fujita, et al. Metformin prevents progression of heart failure in dogs role of AMP-activated protein kinase[J]. Circulation, 2009, 119(19): 2568-2577.
[15]Kevin MP, Michael WKattan, Changhong Yu, et al. The risk of developing coronary artery disease or congestive heart failure, and overall mortality in type 2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis[J]. Acta Diabetol, 2009, 46(2):145-154
[16]Kao J, Tobis J, McClelland RL, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention[J]. Am J Cardiol, 2004, 93(11):1347-1350
[17]McAfee AT, Koro C, Landon J et al. Coronary heart disease outcomes in patients receiving antidiabetic agents[J]. Pharmacoepidemiol Drug Saf, 2007, 16(7):711-725
[18]Gurpreet S. Bhamra Derek J. Hausenloy Sean M. Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening [J]. Basic Res Cardiol, 2008, 103(3): 274-284.
[19]Hardie DG, Hawley SA,　Scott JW. AMP-activated protein kinase-development of the energy sensor concept[J]. J Physiol, 2006, 574(Pt 1):7-15.
[20]Lund SS, Tarnow L, Frandsen M, et al. Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in nonobese patients with type 2 diabetes[J]. Eur J Endocrinol, 2008,158 (1): 35-46.
[21]王红, 杨春红, 玛依拉. 二甲双胍对糖耐量减低患者血清炎症标志物的影响[J]. 现代医药卫生, 2008,24 (6):847-848.
[22]Harden KA, Cowan PA,Velaspuez-Mieyer P, et al. Effects of lifestyle intervention and metformin on weight management and markers of metabolic syndrome in obese adolescents[J]. J Am Acad Nurse Pract, 2007, 19 (7): 368-377.
[23]Saenz A, Fernandez-Esteban I, Mataix A, et al. Metformin monotherapy for type 2 diabetes mellitus [J]. Cochrane Database Syst Rev, 2005, 20(3):CD002966.
[24]王建华, 李清, 胡玉堂. 二甲双胍对高血压合并2 型糖尿病患者血压及血脂的影响[J]. 现代中西医结合杂志, 2008, 17 (24):3733-3735.
[25]Lebovitz HE. Insulin resistance: a common link between type 2 diabetes and cardiovascular disease [J]. Diabetes Obes Metab, 2006, 8 (3): 237-249.
[26]Vitale C, Marazzi G, Volterrani M, et al. Metabolic syndrome[J]. Minerva Med, 2006, 97 (3) :219-229.
[27]Kitabchi AE, Temprosa M, Knowler WC, et al. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin[J]. Diabetes, 2005, 54 (8): 2404-2414.
[28]Misra P, Chakrabarti R. The role of AMP kinase in diabetes [J]. Indian J Med Res, 2007, 125 (3) : 389-398.
[29]Baptista T, Martinez J, Lacruz A, et al. Metformin for prevention of weight gain and insulin resistance with olanzapine: A double-blind placebo-controlled trial[J]. Can JP sychiatry, 2006, 51(3):192-196.
[30]Hayden MS, Ghosh S. Shared principles in NF-kappa B signaling[J]. Cell, 2008, 132 (3) : 344-362.
[31]Isoda K, Young JL, Zirlik A, et al. Metformin inhibits proinflammatory responses and nuclear factor- kappa B in human vascular wall cells[J]. Arterioscler Thromb Vasc Biol, 2006, 26(3):611-617.
[32]Gómez-García A, Martínez Torres G, Ortega-Rtega-Pierres LE. Rosuvastatin and metformin decrease inflammation and oxidative stress in patients with hypertension and dyslipidemia[J]. Rev Esp Cardiol, 2007, 60(12): 1242-1249.
[33]De Jager J, Kooy A, Lehert P, et al. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo controlled trial [J]. J Intern Med, 2005, 257 (1) : 100-109.
[34]Hattori Y, Suzuki K, Hattori S, et al. Metformin inhibits cytokine-induced nuclear factor kappa B activation via AMP-activated protein kinase activation in vascular endothelial cells[J]. Hypertension, 2006, 47 (6): 1183 -1188.
[35]Wilson AM, Ryan MC, Boyle AJ. The novel role of C-reactive protein in cardiovascular disease: risk marker or pathogen [J]. Int J Cardiol, 2006, 106 (3) : 291-297.
[36]顾永辉, 刘超, 武晓泓等. 血糖控制对初发2 型糖尿病患者C-反应蛋白及白细胞介素6水平的影响[J]. 中国临床康复, 2006, 10 (44):63-65.
[37]Eguchi K, Tomizawa H, Ishikawa J, et al. Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes[J]. Hypertens Res, 2007, 30 (1) : 23-30.
[38]Correia S, Carvalho C, Santos MS, et al. Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes[J]. Med Chem, 2008, 4(4):358-364.
[39]Gallo A, Celotto G, Pinton P, et al. Metformin prevents glucose-induced protein kinase-C beta activation in human umbilical vein endothelial cells through an antioxidant mechanism [J]. Diabetes, 2005, 54 (4) : 1123 - 1131.