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Open Access 01-12-2014 | Review

Cardiovascular effects of Glucagon-like peptide 1 (GLP-1) receptor agonists

Authors: Francisco Kerr Saraiva, Andrei C Sposito

Published in: Cardiovascular Diabetology | Issue 1/2014

Abstract

Patients with type 2 diabetes have a several-fold increased risk of developing cardiovascular disease when compared with nondiabetic controls. Myocardial infarction and stroke are responsible for 75% of all death in patients with diabetes, who present a 2-4× increased incidence of death from coronary artery disease. Patients with diabetes are considered for cardiovascular disease secondary prevention because their risk level is similar to that reported in patients without diabetes who have already suffered a myocardial infarction. More recently, with a better risk factors control, mainly in intensive LDL cholesterol targets with statins, a significant decrease in acute cardiovascular events was observed in population with diabetes. Together with other major risk factors, type 2 diabetes must be considered as an important cause of cardiovascular disease.

Glucagon like peptide-1 receptor agonists represent a novel class of anti-hyperglycemic agents that have a cardiac-friendly profile, preserve neuronal cells and inhibit neuronal degeneration, an anti-inflammatory effect in liver protecting it against steatosis, increase insulin sensitivity, promote weight loss, and increase satiety or anorexia.

This review is intended to rationally compile the multifactorial cardiovascular effects of glucagon-like peptide-1 receptor agonists available for the treatment of patients with type 2 diabetes.

Available only for authorised users

Booth GL, Kapral MK, Fung K, Tu JV: Recent trends in cardiovascular complications among men and women with and without diabetes. Diabetes Care. 2006, 29 (1): 32-7. 10.2337/diacare.29.01.06.dc05-0776.CrossRefPubMed

Haffner SJ, Cassells H: Hyperglycemia as a cardiovascular risk factor. Am J Med. 2003, 115 (Suppl 8A): 6S-11S. 10.1016/j.amjmed.2003.09.009.CrossRefPubMed

Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998, 339 (4): 229-34. 10.1056/NEJM199807233390404.CrossRefPubMed

Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC, Sowers JR: Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999, 100 (10): 1134-46. 10.1161/01.CIR.100.10.1134.CrossRefPubMed

Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren WM, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvänne M, Scholte Op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F: European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Atherosclerosis. 2012, 223 (1): 1-68. 10.1016/j.atherosclerosis.2012.05.007.CrossRefPubMed

McIntyre N, Holsworth DC, Turner DS: New interpretation of oral glucose tolerance. Lancet. 1964, 2: 20-21. 10.1016/S0140-6736(64)90011-X.CrossRefPubMed

Creutzfeldt W, Ebert R: New developments in the incretin concept. Diabetologia. 1985, 28: 565-73. 10.1007/BF00281990.CrossRefPubMed

Nauck M, Stockmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986, 29 (1): 46-52. 10.1007/BF02427280.CrossRefPubMed

An Z, Prigeon RL, D’Alessio DA: Improved glycemic control enhances the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2013, 98 (12): 4702-4708. 10.1210/jc.2013-1199.CrossRefPubMed

10.

Kieffer TJ, Habener JF: The glucagon-like peptides. Endocr Rev. 1999, 20 (6): 876-913. 10.1210/edrv.20.6.0385.CrossRefPubMed

11.

Wei Y, Mojsov S: Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995, 358: 219-24. 10.1016/0014-5793(94)01430-9.CrossRefPubMed

12.

Körner M, Stöckli M, Waser B, Reubi JC: GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007, 48: 736-43. 10.2967/jnumed.106.038679.CrossRefPubMed

13.

Lund A, Knop FK, Vilsbøll T: Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes: differences and similarities. Eur J Intern Med. 2014, 25 (5): 407-14. 10.1016/j.ejim.2014.03.005.CrossRefPubMed

14.

Baggio LL, Drucker DJ: Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007, 132 (6): 2131-57. 10.1053/j.gastro.2007.03.054.CrossRefPubMed

15.

Godoy-Matos AF: The role of glucagon on type 2 diabetes at a glance. Diabetol Metab Syndr. 2014, 6 (1): 91-10.1186/1758-5996-6-91.PubMedCentralCrossRefPubMed

16.

De Marinis YZ, Salehi A, Ward CE, Zhang Q, Abdulkader F, Bengtsson M, Braha O, Braun M, Ramracheya R, Amisten S, Habib AM, Moritoh Y, Zang E, Reimann F, Rosengren AH, Shibasaki T, Gribble F, Renström E, Seino S, Eliasson L, Rorsman P: GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab. 2010, 11: 543-553. 10.1016/j.cmet.2010.04.007.PubMedCentralCrossRefPubMed

17.

De Heer J, Rasmussen C, Coy DH, Holst JJ: Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia. 2008, 51: 2263-2270. 10.1007/s00125-008-1149-y.CrossRefPubMed

18.

Little TJ, Pilichiewicz AN, Russo A, Phillips L, Jones KL, Nauck MA, Wishart J, Horowitz M, Feinle-Bisset C: Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. J Clin Endocrinol Metab. 2006, 91 (5): 1916-23. 10.1210/jc.2005-2220.CrossRefPubMed

19.

Flint A, Raben A, Astrup A, Holst JJ: Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998, 101 (3): 515-20. 10.1172/JCI990.PubMedCentralCrossRefPubMed

20.

Dailey MJ, Moran TH: Glucagon-like peptide 1 and appetite. Trends Endocrinol Metab. 2013, 24: 85-91. 10.1016/j.tem.2012.11.008.PubMedCentralCrossRefPubMed

21.

ørskov C, Poulsen SS, Møller M, Holst JJ: Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I. Diabetes. 1996, 45: 832-5. 10.2337/diab.45.6.832.CrossRefPubMed

22.

Pannacciulli N, Bunt JC, Koska J, Bogardus C, Krakoff J: Higher fasting plasma concentrations of glucagon-like peptide 1 are associated with higher resting energy expenditure and fat oxidation rates in humans. Am J Clin Nutr. 2006, 84: 556-60.PubMed

23.

Komatsu M, Takei M, Ishii H, Sato Y: Glucose-stimulated insulin secretion: a newer perspective. J Diabetes Investig. 2013, 4 (6): 511-6. 10.1111/jdi.12094.PubMedCentralCrossRefPubMed

24.

Sussman MA, Völkers M, Fischer K, Bailey B, Cottage CT, Din S, Gude N, Avitabile D, Alvarez R, Sundararaman B, Quijada P, Mason M, Konstandin MH, Malhowski A, Cheng Z, Khan M, McGregor M: Myocardial AKT: the omnipresent nexus. Physiol Rev. 2011, 91: 1023-1070. 10.1152/physrev.00024.2010.PubMedCentralCrossRefPubMed

25.

Cornu M, Modi H, Kawamori D, Kulkarni RN, Joffraud M, Thorens B: Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression. J Biol Chem. 2010, 285 (14): 10538-45. 10.1074/jbc.M109.091116.PubMedCentralCrossRefPubMed

26.

Aroor AR, Sowers JR, Jia G, DeMarco VG: Pleiotropic Effects of the Dipeptidylpeptidase-4 Inhibitors on the Cardiovascular System. Am J Physiol Heart Circ Physiol. 2014, 307 (4): H477-H492. 10.1152/ajpheart.00209.2014.PubMedCentralCrossRefPubMed

27.

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I: SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013, 369 (14): 1317-26. 10.1056/NEJMoa1307684.CrossRefPubMed

28.

White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F: EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013, 369 (14): 1327-35. 10.1056/NEJMoa1305889.CrossRefPubMed

29.

Gupta V: Pleiotropic effects of incretins. Indian J Endocrinol Metab. 2012, 16 (Suppl1): S47-S56. 10.4103/2230-8210.94259.PubMedCentralCrossRefPubMed

30.

Kirkpatrick A, Heo J, Abrol R, Goddard WA: Predicted structure of agonist-bound glucagon-like peptide 1 receptor, a class B G protein-coupled receptor. Proc Natl Acad Sci U S A. 2012, 109 (49): 19988-93. 10.1073/pnas.1218051109.PubMedCentralCrossRefPubMed

31.

Bullock BP, Heller RS, Habener JF: Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology. 1996, 137 (7): 2968-2978.PubMed

32.

Ban K, Kim KH, Cho CK, Sauvé M, Diamandis EP, Backx PH, Drucker DJ, Husain M: Glucagon-like peptide (GLP)-1(9-36)amide-mediated cytoprotection is blocked by exendin(9-39) yet does not require the known GLP-1 receptor. Endocrinology. 2010, 151: 1520-1531. 10.1210/en.2009-1197.CrossRefPubMed

33.

Nyström T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, Sjöholm A: Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004, 287: E1209-E1215. 10.1152/ajpendo.00237.2004.CrossRefPubMed

34.

Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S: Glucagon-like peptide-1 (GLP-1) inhibits advanced glycation end product (AGE)-induced up-regulation of VCAM-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression. Biochem Biophys Res Commun. 2010, 391: 1405-1408. 10.1016/j.bbrc.2009.12.075.CrossRefPubMed

35.

Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M: Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and-independent pathways. Circulation. 2008, 117: 2340-2350. 10.1161/CIRCULATIONAHA.107.739938.CrossRefPubMed

36.

Ussher JR, Drucker DJ: Cardiovascular actions of incretin-based therapies. Circ Res. 2014, 114 (11): 1788-803. 10.1161/CIRCRESAHA.114.301958.CrossRefPubMed

37.

Kuna RS, Girada SB, Asalla S, Vallentyne J, Maddika S, Patterson JT, Smiley DL, DiMarchi RD, Mitra P: Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic ncreatic. Am J Physiol Endocrinol Metab. 2013, 305 (2): E161-70. 10.1152/ajpendo.00551.2012.CrossRefPubMed

38.

Vila Petroff MG, Egan JM, Wang X, Sollott SJ: Glucagon- like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res. 2001, 89: 445-452. 10.1161/hh1701.095716.CrossRefPubMed

39.

Gigoux V, Fourmy D: Acting on hormone receptors with minimal side effect on cell proliferation: a timely challenge illustrated with GLP-1R and GPER. Front Endocrinol. 2013, 4: 50-10.3389/fendo.2013.00050.CrossRef

40.

Xiao YF, Nikolskaya A, Jaye DA, Sigg DC: Glucagon-like peptide-1 enhances cardiac L-type Ca2+ currents via activation of the cAMP-dependent protein kinase A pathway. Cardiovasc Diabetol. 2011, 10: 6-10.1186/1475-2840-10-6.PubMedCentralCrossRefPubMed

41.

Rose BA, Force T, Wang Y: Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev. 2010, 90: 1507-1546. 10.1152/physrev.00054.2009.CrossRefPubMed

42.

Chang G, Zhang D, Yu H, Zhang P, Wang Y, Zheng A, Qin S: Cardioprotective effects of exenatide against oxidative stress-induced injury. Int J Mol Med. 2013, 32 (5): 1011-20.PubMed

43.

Shan PR, Xu WW, Huang ZQ, Pu J, Huang WJ: Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats. World J Emerg Med. 2014, 5 (2): 122-7. 10.5847/wjem.j.issn.1920-8642.2014.02.008.PubMedCentralCrossRefPubMed

44.

Ravassa S, Zudaire A, Carr RD, Díez J: Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am J Physiol Heart Circ Physiol. 2011, 300: H1361-H1372. 10.1152/ajpheart.00885.2010.CrossRefPubMed

45.

Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP: Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation. 2004, 110: 955-961. 10.1161/01.CIR.0000139339.85840.DD.CrossRefPubMed

46.

Moberly SP, Mather KJ, Berwick ZC, Owen MK, Goodwill AG, Casalini ED, Hutchins GD, Green MA, Ng Y, Considine RV, Perry KM, Chisholm RL, Tune JD: Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus. Basic Res Cardiol. 2013, 108 (4): 365-10.1007/s00395-013-0365-x.PubMedCentralCrossRefPubMed

47.

Moberly SP, Berwick ZC, Kohr M, Svendsen M, Mather KJ, Tune JD: Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow. Exp Biol Med. 2012, 237 (3): 334-42. 10.1258/ebm.2011.011288.CrossRef

48.

Zhao TC: Glucagon-like peptide-1 (GLP-1) and protective effects in cardiovascular disease: a new therapeutic approach for myocardial protection. Cardiovasc Diabetol. 2013, 12: 90-10.1186/1475-2840-12-90.PubMedCentralCrossRefPubMed

49.

Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP: Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail. 2006, 12 (9): 694-699. 10.1016/j.cardfail.2006.08.211.CrossRefPubMed

50.

Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern GJ, Maher TD, Dean DA, Bailey SH, Marrone G, Benckart DH, Elahi D, Shannon RP: Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol. 2007, 100 (5): 824-829. 10.1016/j.amjcard.2007.05.022.CrossRefPubMed

51.

Barragán JM, Rodríguez RE, Blázquez E: Changes in arterial blood pressure and heart rate induced by glucagon-like peptide-1-(7-36 amide) in rats. Am J Physiol. 1994, 266 (3): E459-E466.PubMed

52.

Robinson LE, Holt TA, Rees K, Randeva HS, O’Hare JP: Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis.BMJ Open 2013, 3(1). doi:10.1136/bmjopen-2012-001986.,

53.

Edwards CM, Todd JF, Ghatei MA, Bloom SR: Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects. Clin Sci. 1998, 95 (6): 719-724. 10.1042/CS19980050.CrossRefPubMed

54.

Ceriello A, Novials A, Canivell S, La Sala L, Pujadas G, Esposito K, Testa R, Bucciarelli L, Rondinelli M, Genovese S: Simultaneous GLP-1 and insulin administration acutely enhances their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes. Diabetes Care. 2014, 37 (7): 1938-43. 10.2337/dc13-2618.CrossRefPubMed

55.

Erdogdu O, Nathanson D, Sjöholm A, Nyström T, Zhang Q: Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor. Mol Cell Endocrinol. 2010, 325: 26-35. 10.1016/j.mce.2010.04.022.CrossRefPubMed

56.

Wang D, Luo P, Wang Y, Li W, Wang C, Sun D, Zhang R, Su T, Ma X, Zeng C, Wang H, Ren J, Cao F: Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism. Diabetes. 2013, 62 (5): 1697-708. 10.2337/db12-1025.PubMedCentralCrossRefPubMed

57.

Batchuluun B, Inoguchi T, Sonoda N, Sasaki S, Inoue T, Fujimura Y, Miura D, Takayanagi R: Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells. Atherosclerosis. 2014, 232 (1): 156-64. 10.1016/j.atherosclerosis.2013.10.025.CrossRefPubMed

58.

Kelly AS, Richard M, Bergenstal RM, Gonzalez-Campoy JM, Harold Katz H, Bank AJ: Effects of Exenatide vs. Metformin on endothelial function in obese patients with pre-diabetes: a randomized trial. Cardiovasc Diabetol. 2012, 11: 64-10.1186/1475-2840-11-64.PubMedCentralCrossRefPubMed

59.

Basu A, Charkoudian N, Schrage W, Rizza RA, Basu R, Joyner MJ: Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride. Am J Physiol Endocrinol Metab. 2007, 293: E1289-E1295. 10.1152/ajpendo.00373.2007.CrossRefPubMed

60.

Ceriello A, Esposito K, Testa R, Bonfigli AR, Marra M, Giugliano D: The possible protective role of glucagon-like peptide 1 on endothelium during the meal and evidence for an “endothelial resistance” to glucagon-like peptide 1 in diabetes. Diabetes Care. 2011, 34: 697-702. 10.2337/dc10-1949.PubMedCentralCrossRefPubMed

61.

Gutzwiller JP, Tschopp S, Bock A, Zehnder CE, Huber AR, Kreyenbuehl M, Gutmann H, Drewe J, Henzen C, Goeke B, Beglinger C: Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004, 89 (6): 3055-61. 10.1210/jc.2003-031403.CrossRefPubMed

62.

Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, Simpson JA, Drucker DJ: GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med. 2013, 19 (5): 567-75. 10.1038/nm.3128.CrossRefPubMed

63.

Arakawa M, Mita T, Azuma K, Ebato C, Goto H, Nomiyama T, Fujitani Y, Hirose T, Kawamori R, Watada H: Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes. 2010, 59: 1030-1037. 10.2337/db09-1694.PubMedCentralCrossRefPubMed

64.

Piotrowski K, Becker M, Zugwurst J, Biller-Friedmann I, Spoettl G, Greif M, Leber AW, Becker A, Laubender RP, Lebherz C, Goeke B, Marx N, Parhofer KG, Lehrke M: Circulating concentrations of GLP-1 are associated with coronary atherosclerosis in humans. Cardiovasc Diabetol. 2013, 12: 117-10.1186/1475-2840-12-117.PubMedCentralCrossRefPubMed

65.

Goto H, Nomiyama T, Mita T, Yasunari E, Azuma K, Komiya K, Arakawa M, Jin WL, Kanazawa A, Kawamori R, Fujitani Y, Hirose T, Watada H: Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury. Biochem Biophys Res Commun. 2011, 405: 79-84. 10.1016/j.bbrc.2010.12.131.CrossRefPubMed

66.

Nagashima M, Watanabe T, Terasaki M, Tomoyasu M, Nohtomi K, Kim-Kaneyama J, Miyazaki A, Hirano T: Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice. Diabetologia. 2011, 54: 2649-2659. 10.1007/s00125-011-2241-2.PubMedCentralCrossRefPubMed

67.

Tashiro Y, Sato K, Watanabe T, Nohtomi K, Terasaki M, Nagashima M, Hirano T: A glucagon-like peptide-1 analog liraglutide suppresses macrophage foam cell formation and atherosclerosis. Peptides. 2014, S0196-9781 (13): 00431-2.

68.

Liu H, Dear AE, Knudsen LB, Simpson RW: A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules. J Endocrinol. 2009, 201: 59-66. 10.1677/JOE-08-0468.CrossRefPubMed

69.

Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MA: Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011, 34 (1): 90-5. 10.2337/dc10-1393.PubMedCentralCrossRefPubMed

70.

Ratner R, Han J, Nicewarner D, Yushmanova I, Hoogwerf BJ, Shen L: Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 22-10.1186/1475-2840-10-22.PubMedCentralCrossRefPubMed

71.

Nathanson D, Ullman B, Löfström U, Hedman A, Frick M, Sjöholm A, Nyström T: Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: a double-blind, randomised controlled clinical trial of efficacy and safety. Diabetologia. 2012, 55 (4): 926-35. 10.1007/s00125-011-2440-x.CrossRefPubMed

72.

Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP: Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004, 109 (8): 962-5. 10.1161/01.CIR.0000120505.91348.58.CrossRefPubMed

73.

Woo JS, Kim W, Ha SJ, Kim JB, Kim SJ, Kim WS, Seon HJ, Kim KS: Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study. Arterioscler Thromb Vasc Biol. 2013, 33 (9): 2252-60. 10.1161/ATVBAHA.113.301586.CrossRefPubMed

74.

Hermansen K, Bækdal TA, Düring M, Pietraszek A, Mortensen LS, Jørgensen H, Flint A: Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial. Diab Obesity Metabol. 2013, 15: 1040-1048. 10.1111/dom.12133.CrossRef

75.

Meloni AR, DeYoung MB, Han J, Best JH, Grimm M: Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals. Cardiovasc Diabetol. 2013, 12: 48-10.1186/1475-2840-12-48.PubMedCentralCrossRefPubMed

76.

Zhao T, Parikh P, Bhashyam S, Bolukoglu H, Poornima I, Shen YT, Shannon RP: Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts. J Pharmacol Exp Ther. 2006, 317: 1106-1113. 10.1124/jpet.106.100982.CrossRefPubMed

77.

Hattori Y, Jojima T, Tomizawa A, Satoh H, Hattori S, Kasai K, Hayashi T: A glucagon-like peptide-1 (GLP-1) analogue, liraglutide, upregulates nitric oxide production and exerts anti-inflammatory action in endothelial cells. Diabetologia. 2010, 53 (10): 2256-63. 10.1007/s00125-010-1831-8.CrossRefPubMed

78.

Read PA, Khan FZ, Dutka DP: Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart. 2012, 98 (5): 408-13. 10.1136/hrt.2010.219345.CrossRefPubMed

79.

Chiquette E, Toth PP, Ramirez G, Cobble M, Chilton R: Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers. Vasc Health Risk Manag. 2012, 8: 621-9.PubMedCentralPubMed

Title: Cardiovascular effects of Glucagon-like peptide 1 (GLP-1) receptor agonists
Authors: Francisco Kerr Saraiva
Andrei C Sposito
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Cardiovascular Diabetology / Issue 1/2014
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-014-0142-7

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