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Current Diabetes Reports

Erschienen in:

01.05.2014 | Pharmacologic Treatment of Type 2 Diabetes (A Vella, Section Editor)

Cardiovascular Actions of GLP-1 and Incretin-Based Pharmacotherapy

verfasst von: Angelo Avogaro, Saula Vigili de Kreutzenberg, Gian Paolo Fadini

Erschienen in: Current Diabetes Reports | Ausgabe 5/2014

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Abstract

Incretin-based therapy became recently available as antihyperglycemic treatment for patients with type 2 diabetes (T2DM). Incretin therapy comprises glucagon-like peptide receptor agonists (GLP-1RA) and dipeptidyl-peptidase 4 inhibitors (DPP4-I): these classes of drugs not only have the ability to reduce blood glucose, but also can exert several cardioprotective effects. They have been shown to positively influence some risk factors for cardiovascular disease (CVD), to improve endothelial function, and to directly affect cardiac function. For these reasons incretins are considered not only antidiabetic drugs, but also cardiovascular effective. The first clinical trials aimed to demonstrate the safety of DPP4 inhibitors have been recently published: their clinical significance will be discussed in light of the prior experimental findings.

Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006;114:2850–70.PubMed

Avogaro A, de Kreutzenberg SV, Fadini G. Endothelial dysfunction: causes and consequences in patients with diabetes mellitus. Diabetes Res Clin Pract. 2008;82 Suppl 2:S94–101.PubMed

Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol. 2009;53(5 Suppl):S35–42.PubMedCentralPubMed

Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376:124–36.PubMed

Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151:394–403.PubMed

6.•

Ou X, O'Leary HA, Broxmeyer HE. Implications of DPP4 modification of proteins that regulate stem/progenitor and more mature cell types. Blood. 2013;122:161–9. Extensive review on the role of DPP4 inhibition on different proteins other than GLP-1.PubMed

Thorens B, Porret A, Buhler L, Deng SP, Morel P, Widmann C. Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor. Diabetes. 1993;42:1678–82.PubMed

Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology. 1996;137:2968–78.PubMed

van Genugten RE, Moller-Goede DL, van Raalte DH, Diamant M. Extra-pancreatic effects of incretin-based therapies: potential benefit for cardiovascular-risk management in type 2 diabetes. Diabetes Obes Metab. 2013;15:593–606.PubMed

10.

Schwartz EA, Koska J, Mullin MP, Syoufi I, Schwenke DC, Reaven PD. Exenatide suppresses postprandial elevations in lipids and lipoproteins in individuals with impaired glucose tolerance and recent onset type 2 diabetes mellitus. Atherosclerosis. 2010;212:217–22.PubMed

11.

Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Wu Y, et al. One-year treatment with exenatide vs insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis. 2010;212:223–9.PubMed

12.

Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, et al. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met + TZD). Diabetes Care. 2009;32:1224–30.PubMedCentralPubMed

13.

Monami M, Lamanna C, Desideri CM, Mannucci E. DPP-4 inhibitors and lipids: systematic review and meta-analysis. Adv Ther. 2012;29:14–25.PubMed

14.

Eliasson B, Moller-Goede D, Eeg-Olofsson K, Wilson C, Cederholm J, Fleck P, et al. Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomized double-blind placebo-controlled study. Diabetologia. 2012;55:915–25.PubMed

15.

Xiao C, Bandsma RH, Dash S, Szeto L, Lewis GF. Exenatide, a glucagon-like peptide-1 receptor agonist, acutely inhibits intestinal lipoprotein production in healthy humans. Arterioscler Thromb Vasc Biol. 2012;32:1513–9.PubMed

16.

Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, et al. Liraglutide vs glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomized, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373:473–81.PubMed

17.

Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010;23:334–9.PubMed

18.

Wang B, Zhong J, Lin H, Zhao Z, Yan Z, He H, et al. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab. 2013;15:737–49.PubMed

19.

Gutzwiller JP, Tschopp S, Bock A, Zehnder CE, Huber AR, Kreyenbuehl M, et al. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004;89:3055–61.PubMed

20.

Yamamoto H, Lee CE, Marcus JN, Williams TD, Overton JM, Lopez ME, et al. Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin Invest. 2002;110:43–52.PubMedCentralPubMed

21.

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;117:2340–50.PubMed

22.••

Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, et al. GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med. 2013;19:567–75. A molecular clarification of the natriuretic effect of GLP-1RA is provided for the first time.PubMed

23.

Jackson EK, Mi Z. Sitagliptin augments sympathetic enhancement of the renovascular effects of angiotensin II in genetic hypertension. Hypertension. 2008;51:1637–42.PubMedCentralPubMed

24.

Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans. Hypertension. 2010;56:728–33.PubMedCentralPubMed

25.

Liu L, Liu J, Wong WT, Tian XY, Lau CW, Wang YX, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism. Hypertension. 2012;60:833–41.PubMed

26.

Kirino Y, Sato Y, Kamimoto T, Kawazoe K, Minakuchi K, Nakahori Y. Interrelationship of dipeptidyl peptidase IV (DPP4) with the development of diabetes, dyslipidemia and nephropathy: a streptozotocin-induced model using wild-type and DPP4-deficient rats. J Endocrinol. 2009;200:53–61.PubMed

27.

Girardi AC, Fukuda LE, Rossoni LV, Malnic G, Reboucas NA. Dipeptidyl peptidase IV inhibition downregulates Na + - H + exchanger NHE3 in rat renal proximal tubule. Am J Physiol Renal Physiol. 2008;294:F414–22.PubMed

28.

Tanaka T, Nangaku M, Nishiyama A. The role of incretins in salt-sensitive hypertension: the potential use of dipeptidyl peptidase-IV inhibitors. Curr Opin Nephrol Hypertens. 2011;20:476–81.PubMed

29.

Pacheco BP, Crajoinas RO, Couto GK, Davel AP, Lessa LM, Rossoni LV, et al. Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats. J Hypertens. 2011;29:520–8.PubMed

30.

Boerrigter G, Costello-Boerrigter LC, Harty GJ, Lapp H, Burnett Jr JC. Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation. Am J Physiol Regul Integr Comp Physiol. 2007;292:R897–901.PubMed

31.

Mistry GC, Maes AL, Lasseter KC, Davies MJ, Gottesdiener KM, Wagner JA, et al. Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension. J Clin Pharmacol. 2008;48:592–8.PubMed

32.

Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, et al. Efficacy and safety of exenatide once weekly vs sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomized trial. Lancet. 2010;376:431–9.PubMed

33.

Horton ES, Silberman C, Davis KL, Berria R. Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010;33:1759–65.PubMedCentralPubMed

34.

Koren S, Shemesh-Bar L, Tirosh A, Peleg RK, Berman S, Hamad RA, et al. The effect of sitagliptin vs glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients. Diabetes Technol Ther. 2012;14:561–7.PubMed

35.

Cobble ME, Frederich R. Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data. Cardiovasc Diabetol. 2012;11:6.PubMedCentralPubMed

36.

Horie Y, Kanada S, Watada H, Sarashina A, Taniguchi A, Hayashi N, et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor linagliptin: a 4-week multicenter, randomized, double-blind, placebo-controlled phase IIa study in Japanese type 2 diabetes patients. Clin Ther. 2011;33:973–89.PubMed

37.

Ohnuma K, Dang NH, Morimoto C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol. 2008;29:295–301.PubMed

38.

Zhong J, Rao X, Deiuliis J, Braunstein Z, Narula V, Hazey J, et al. A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-induced visceral inflammation. Diabetes. 2013;62:149–57.PubMedCentralPubMed

39.••

Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM, et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011;60:1917–25. The first demonstration that DPP4 is an actively secreted adipokine by visceral adipose tissues.PubMedCentralPubMed

40.

Ferreira L, Teixeira-de-Lemos E, Pinto F, Parada B, Mega C, Vala H, et al. Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat). Mediat Inflamm. 2010;2010:592760.

41.

Dobrian AD, Ma Q, Lindsay JW, Leone KA, Ma K, Coben J, et al. Dipeptidyl peptidase IV inhibitor sitagliptin reduces local inflammation in adipose tissue and in pancreatic islets of obese mice. Am J Physiol Endocrinol Metab. 2011;300:E410–21.PubMedCentralPubMed

42.

Ta NN, Schuyler CA, Li Y, Lopes-Virella MF, Huang Y. DPP-4 (CD26) inhibitor alogliptin inhibits atherosclerosis in diabetic apolipoprotein E-deficient mice. J Cardiovasc Pharmacol. 2011;58:157–66.PubMedCentralPubMed

43.

Shah Z, Kampfrath T, Deiuliis JA, Zhong J, Pineda C, Ying Z, et al. Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation. 2011;124:2338–49.PubMed

44.

Vittone F, Liberman A, Vasic D, Ostertag R, Esser M, Walcher D, et al. Sitagliptin reduces plaque macrophage content and stabilizes arteriosclerotic lesions in Apoe (-/-) mice. Diabetologia. 2012;55:2267–75.PubMed

45.

Kroller-Schon S, Knorr M, Hausding M, Oelze M, Schuff A, Schell R, et al. Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition. Cardiovasc Res. 2012;96:140–9.PubMed

46.

Matheeussen V, Waumans Y, Martinet W, Van Goethem S, Van der Veken P, Scharpe S, et al. Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis. Basic Res Cardiol. 2013;108:350.PubMed

47.

Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012;35:2076–82.PubMedCentralPubMed

48.

Barbieri M, Rizzo MR, Marfella R, Boccardi V, Esposito A, Pansini A, et al. Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors. Atherosclerosis. 2013;227:349–54.PubMed

49.

Makdissi A, Ghanim H, Vora M, Green K, Abuaysheh S, Chaudhuri A, et al. Sitagliptin exerts an anti-inflammatory action. J Clin Endocrinol Metab. 2012;97:3333–41.PubMedCentralPubMed

50.

Satoh-Asahara N, Sasaki Y, Wada H, Tochiya M, Iguchi A, Nakagawachi R, et al. A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients. Metabolism. 2013;62:347–51.PubMed

51.

Shiraki A, Oyama J, Komoda H, Asaka M, Komatsu A, Sakuma M, et al. The glucagon-like peptide 1 analog liraglutide reduces TNF-alpha-induced oxidative stress and inflammation in endothelial cells. Atherosclerosis. 2012;221:375–82.PubMed

52.

Wu JD, Xu XH, Zhu J, Ding B, Du TX, Gao G, et al. Effect of exenatide on inflammatory and oxidative stress markers in patients with type 2 diabetes mellitus. Diabetes Technol Ther. 2011;13:143–8.PubMed

53.

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

54.

Burgmaier M, Heinrich C, Marx N. Cardiovascular effects of GLP-1 and GLP-1-based therapies: implications for the cardiovascular continuum in diabetes? Diabet Med. 2013;30:289–99.PubMed

55.•

Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012;33:187–215. Extensive review on the cardiovascular effect of incretins.PubMedCentralPubMed

56.

Tomas E, Stanojevic V, Habener JF. GLP-1-derived nonapeptide GLP-1(28-36) amide targets to mitochondria and suppresses glucose production and oxidative stress in isolated mouse hepatocytes. Regul Pept. 2011;167:177–84.PubMed

57.

Christopherson II KW, Hangoc G, Mantel CR, Broxmeyer HE. Modulation of hematopoietic stem cell homing and engraftment by CD26. Science. 2004;305:1000–3.PubMed

58.

DiPersio JF. Diabetic stem-cell "mobilopathy". N Engl J Med. 2011;365:2536–8.PubMed

59.

Zaruba MM, Theiss HD, Vallaster M, Mehl U, Brunner S, David R, et al. Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell. 2009;4:313–23.PubMed

60.•

Fadini GP, Boscaro E, Albiero M, Menegazzo L, Frison V, de Kreutzenberg, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care. 2010;33:1607–9. The first report of an effect of DPP4-I on endothelial progenitor cells in vivo, in diabetic patients.PubMedCentralPubMed

61.

Shigeta T, Aoyama M, Bando YK, Monji A, Mitsui T, Takatsu M, et al. Dipeptidyl peptidase-4 modulates left ventricular dysfunction in chronic heart failure via angiogenesis-dependent and -independent actions. Circulation. 2012;126:1838–51.PubMed

62.

Fadini GP, Albiero M, Seeger F, Poncina N, Menegazzo L, Angelini A, et al. Stem cell compartmentalization in diabetes and high cardiovascular risk reveals the role of DPP-4 in diabetic stem cell mobilopathy. Basic Res Cardiol. 2013;108:313.PubMed

63.

Brandt I, Lambeir AM, Ketelslegers JM, Vanderheyden M, Scharpe S, De Meester I. Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. Clin Chem. 2006;52:82–7.PubMed

64.

Yin M, Sillje HH, Meissner M, van Gilst WH, de Boer RA. Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of postmyocardial infarction heart failure. Cardiovasc Diabetol. 2011;10:85.PubMedCentralPubMed

65.

Lourenco P, Frioes F, Silva N, Guimaraes JT, Bettencourt P. Dipeptidyl peptidase IV and mortality after an acute heart failure episode. J Cardiovasc Pharmacol. 2013;62:138–42.PubMed

66.

Pala L, Pezzatini A, Dicembrini I, Ciani S, Gelmini S, Vannelli BG, et al. Different modulation of dipeptidyl peptidase-4 activity between microvascular and macrovascular human endothelial cells. Acta Diabetol. 2012;49 Suppl 1:S59–63.PubMed

67.

Matsubara J, Sugiyama S, Sugamura K, Nakamura T, Fujiwara Y, Akiyama E, et al. A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice. J Am Coll Cardiol. 2012;59:265–76.PubMed

68.

Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, et al. 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:E1209–15.PubMed

69.

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:E1289–95.PubMed

70.

Forst T, Michelson G, Ratter F, Weber MM, Anders S, Mitry M, et al. Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet Med. 2012;29:1115–8.PubMed

71.

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.PubMedCentralPubMed

72.

Ceriello A, Novials A, Ortega E, Canivell S, La Sala L, Pujadas G, et al. Glucagon-like peptide 1 reduces endothelial dysfunction, inflammation, and oxidative stress induced by both hyperglycemia and hypoglycemia in type 1 diabetes. Diabetes Care. 2013;36:2346–50.PubMed

73.

Noda Y, Miyoshi T, Oe H, Ohno Y, Nakamura K, Toh N, et al. Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in nondiabetic subjects: a preliminary report. Cardiovasc Diabetol. 2013;12:8.PubMedCentralPubMed

74.

Tesauro M, Schinzari F, Adamo A, Rovella V, Martini F, Mores N, et al. Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome. Diabetes Care. 2013;36:683–9.PubMedCentralPubMed

75.

Kelly AS, Bergenstal RM, Gonzalez-Campoy JM, Katz H, Bank AJ. Effects of exenatide vs metformin on endothelial function in obese patients with prediabetes: a randomized trial. Cardiovasc Diabetol. 2012;11:64.PubMedCentralPubMed

76.

Matsui T, Nishino Y, Takeuchi M, Yamagishi S. Vildagliptin blocks vascular injury in thoracic aorta of diabetic rats by suppressing advanced glycation end product-receptor axis. Pharmacol Res. 2011;63:383–8.PubMed

77.

Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Sitagliptin augments protective effects of GLP-1 against advanced glycation end product receptor axis in endothelial cells. Horm Metab Res. 2011;43:731–4.PubMed

78.

Maeda S, Matsui T, Yamagishi S. Vildagliptin inhibits oxidative stress and vascular damage in streptozotocin-induced diabetic rats. Int J Cardiol. 2012;158:171–3.PubMed

79.

Ojima A, Ishibashi Y, Matsui T, Maeda S, Nishino Y, Takeuchi M, et al. Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end product-induced protein arginine methyltranferase-1 expression. Am J Pathol. 2013;182:132–41.PubMed

80.

Schisano B, Harte AL, Lois K, Saravanan P, Al-Daghri N, Al-Attas O, et al. GLP-1 analogue, Liraglutide protects human umbilical vein endothelial cells against high glucose induced endoplasmic reticulum stress. Regul Pept. 2012;174:46–52.PubMed

81.•

Sauve M, Ban K, Momen MA, Zhou YQ, Henkelman RM, Husain M, et al. Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice. Diabetes. 2010;59:1063–73. The first molecular evidence on the effect of DPP4 deletion in the heart.PubMedCentralPubMed

82.

Chinda K, Palee S, Surinkaew S, Phornphutkul M, Chattipakorn S, Chattipakorn N. Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury. Int J Cardiol. 2013;167:451–7.PubMed

83.

Koska J, Schwartz EA, Mullin MP, Schwenke DC, Reaven PD. Improvement of postprandial endothelial function after a single dose of exenatide in individuals with impaired glucose tolerance and recent-onset type 2 diabetes. Diabetes Care. 2010;33:1028–30.PubMedCentralPubMed

84.

Patil HR, Al Badarin FJ, Al Shami HA, Bhatti SK, Lavie CJ, Bell DS, et al. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol. 2012;110:826–33.PubMed

85.

Monami M, Ahren B, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2013;15:112–20.PubMed

86.

Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, et al. 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;34:90–5.PubMedCentralPubMed

87.

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:E001986.

88.

Nathanson D, Zethelius B, Berne C, Holst JJ, Sjoholm A, Nystrom T. Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease. Diabetologia. 2010;53:277–80.PubMed

89.

Nathanson D, Zethelius B, Berne C, Lind L, Andren B, Ingelsson E, et al. Plasma levels of glucagon like peptide-1 associate with diastolic function in elderly men. Diabet Med. 2011;28:301–5.PubMed

90.

Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004;109:962–5.PubMed

91.

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;98:408–13.PubMed

92.

Thrainsdottir I, Malmberg K, Olsson A, Gutniak M, Ryden L. Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diab Vasc Dis Res. 2004;1:40–3.PubMed

93.

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;12:694–9.PubMed

94.

Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern Jr GJ, Maher TD, et al. 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;100:824–9.PubMed

95.

Munaf M, Pellicori P, Allgar V, Wong K. A meta-analysis of the therapeutic effects of glucagon-like Peptide-1 agonist in heart failure. Int J Pept. 2012;2012:249827.PubMedCentralPubMed

96.

Halbirk M, Norrelund H, Moller N, Holst JJ, Schmitz O, Nielsen R, et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol. 2010;298:H1096–102.PubMed

97.

Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;33:1491–9.PubMed

98.

Lonborg J, Kelbaek H, Vejlstrup N, Botker HE, Kim WY, Holmvang L, et al. Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ Cardiovasc Interv. 2012;5:288–95.PubMed

99.

Read PA, Khan FZ, Heck PM, Hoole SP, Dutka DP. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging. 2010;3:195–201.PubMed

100.

White WB, Bakris GL, Bergenstal RM, Cannon CP, Cushman WC, Fleck P, et al. EXamination of cArdiovascular outcoMes with alogliptIN vs standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. Am Heart J. 2011;162:620–6. e621.PubMed

101.

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study. Am Heart J. 2011;162:818–25. e816.PubMed

102.••

White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–35. The first randomized controlled trial reporting safety for alogliptin in post-AMI T2DM patients.PubMed

103.••

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–26. The first randomized controlled trial reporting safety for saxagliptin in high risk T2DM patients.PubMed

Titel: Cardiovascular Actions of GLP-1 and Incretin-Based Pharmacotherapy
verfasst von: Angelo Avogaro
Saula Vigili de Kreutzenberg
Gian Paolo Fadini
Publikationsdatum: 01.05.2014
Verlag: Springer US
Erschienen in: Current Diabetes Reports / Ausgabe 5/2014
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-014-0483-3

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Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

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