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Inkretine: Gibt es kardiovaskuläre Effekte?

Incretins: Do They Exert Cardiovascular Effects?

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Zusammenfassung

Die physiologischen Effekte des Inkretinhormons „glucagon- like peptide“-(GLP-)1 haben dazu geführt, dass inkretinbasierte Therapieformen mit GLP-1-Analoga und Dipeptidylpeptidase-(DPP-)4-Inhibitoren mittlerweile einen festen Platz in der Therapie des Typ-2-Diabetes haben. Dies liegt nicht nur an dem glucoseabhängigen insulinotropen Effekt von GLP-1 und an den günstigen Effekten auf die Beta-Zell-Funktion und möglicherweise Beta-Zell-Masse, sondern auch an dem günstigen Einfluss auf das Körpergewicht.

In letzter Zeit mehren sich die Daten zu positiven kardiovaskulären Eigenschaften von GLP-1. In Tiermodellen verbessert GLP-1 die linksventrikuläre Leistung und vermindert Myokardschäden bei Ischämie. In klinischen Studien mit GLP-1-Analoga wurden eine Absenkung und Normalisierung erhöhter Blutdruckwerte beobachtet und ein Teil der tierexperimentellen Daten nach Myokardinfarkt oder nach invasiven kardiologischen oder kardiochirurgischen Eingriffen bestätigt. Ebenso zeigten sich Verbesserungen kardiovaskulärer Surrogatparameter unter inkretinbasierten Therapien. Dieser Übersichtsartikel gibt einen Überblick über die kardiovaskulären Effekte von GLP-1 und inkretinbasierten Behandlungsformen.

Abstract

The physiological effects of the incretin hormone glucagon-like peptide-(GLP-)1 have contributed to the important role that incretin-based therapies with GLP-1 analogs or dipeptidyl peptidase-(DPP-)4 inhibitors already play in type 2 diabetes treatment. This development is not only due to the glucose-dependent insulinotropic effect of GLP-1 as well as the positive effects on beta cell function and, probably, beta cell mass, but also to the beneficial effects on body weight.

Lately, the data on positive cardiovascular effects of GLP-1 have been growing. In animal models, GLP-1 improves left ventricular function and diminishes myocardial defects in ischemia models. In clinical studies with GLP-1 analogs, a normalization of blood pressure was observed and some of the data from animal studies after myocardial infarction or after invasive cardiologic or cardiosurgical interventions were also found under clinical conditions in humans. Additionally, an improvement of cardiovascular surrogate parameters was observed with incretin-based therapies. This review gives an overview on the cardiovascular effects of GLP-1 and incretin-based therapies.

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Literatur

  1. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007:132:2131–57.

    Article  PubMed  CAS  Google Scholar 

  2. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab 2004;287:E199–206.

    Article  PubMed  CAS  Google Scholar 

  3. Cornu M, Yang JY, Jaccard E, et al. Glucagon-like peptide-1 protects beta-cells against apoptosis by increasing the activity of an IGF-2/IGF-1 receptor autocrine loop. Diabetes 2009;58:1816–25.

    Article  PubMed  CAS  Google Scholar 

  4. Buteau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival. Diabetes Metab 2008;34:Suppl 2:S73–7.

    Article  PubMed  CAS  Google Scholar 

  5. Farilla L, Bulotta A, Hirshberg B, et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003;144:5149–58.

    Article  PubMed  CAS  Google Scholar 

  6. Perfetti R, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 2000;141:4600–5.

    Article  PubMed  CAS  Google Scholar 

  7. Stoffers DA, Kieffer TJ, Hussain MA, et al. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 2000;49:741–8.

    Article  PubMed  CAS  Google Scholar 

  8. Nyström T, Gonon AT, Sjoholm A, Pernow J. Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul Pept 2005;125:173–7.

    Article  PubMed  CAS  Google Scholar 

  9. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997;273:E981–8.

    PubMed  CAS  Google Scholar 

  10. Nauck MA, Heimesaat MM, Ørskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301–7.

    Article  PubMed  CAS  Google Scholar 

  11. Nauck MA, Kleine N, Ørskov C, et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1(7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:741–4.

    Article  PubMed  CAS  Google Scholar 

  12. Nauck MA. Unraveling the science of incretin biology. Am J Med 2009;122:Suppl:S3–10.

    Article  PubMed  Google Scholar 

  13. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995;80:952–7.

    Article  PubMed  CAS  Google Scholar 

  14. Aschner P, Kipnes MS, Lunceford JK, et al., for the Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006;29:2632–7.

    Article  PubMed  CAS  Google Scholar 

  15. Barnett AH. New treatments in type 2 diabetes: a focus on the incretin-based therapies. Clin Endocrinol (Oxf) 2009;70:343–53.

    Article  CAS  Google Scholar 

  16. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and metaanalysis. JAMA 2007;298:194–206.

    Article  PubMed  CAS  Google Scholar 

  17. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696–705.

    Article  PubMed  CAS  Google Scholar 

  18. Mentlein R. Dipeptidyl-peptidase IV (CD26) — role in the inactivation of regulatory peptides. Regul Pept 1999;85:9–24.

    Article  PubMed  CAS  Google Scholar 

  19. Gilbert MP, Pratley RE. Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus. Am J Med 2009;122:Suppl:S11–24.

    Article  PubMed  Google Scholar 

  20. DeFronzo RA, Okerson T, Viswanathan P, et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin 2008;24:2943–52.

    Article  PubMed  CAS  Google Scholar 

  21. Stonehouse A, Okerson T, Kendall D, Maggs D. Emerging incretin-based therapies for type 2 diabetes: incretin mimetics and DPP-4 inhibitors. Curr Diabetes Rev 2008;4:101–9.

    Article  PubMed  CAS  Google Scholar 

  22. Knop FK, Holst JJ, VilsbØll T. Replacing SUs with incretin-based therapies for type 2 diabetes mellitus: challenges and feasibility. IDrugs 2008;11:497–501.

    PubMed  CAS  Google Scholar 

  23. Ban K, Noyan-Ashraf MH, Hoefer J, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  24. Holst JJ, Deacon CF. Glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus. Curr Opin Pharmacol 2004;4:589–96.

    Article  PubMed  CAS  Google Scholar 

  25. Buse JB, Rosenstock J, Sesti G, et al., LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39–47.

    Article  PubMed  CAS  Google Scholar 

  26. Garber A, Henry R, Ratner R, et al., LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009;373:473–81.

    Article  PubMed  CAS  Google Scholar 

  27. Marre M, Shaw J, Brändle M, et al., LEAD-1 SU Study Group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med 2009;26:268–78.

    Article  PubMed  CAS  Google Scholar 

  28. Nauck M, Frid A, Hermansen K, et al., LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009;32:84–90.

    Article  PubMed  CAS  Google Scholar 

  29. Russell-Jones D, Vaag A, Schmitz O, et al., Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia 2009;52:2046–55.

    Article  PubMed  CAS  Google Scholar 

  30. Zinman B, Gerich J, Buse JB, et al., LEAD-4 Study Investigators. 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.

    Article  PubMed  CAS  Google Scholar 

  31. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092–100.

    Article  PubMed  CAS  Google Scholar 

  32. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083–91.

    Article  PubMed  CAS  Google Scholar 

  33. Buse JB, Henry RR, Han J, et al, for the Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628–35.

    Article  PubMed  CAS  Google Scholar 

  34. Sokos GG, Bolukoglu H, German J, 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.

    Article  PubMed  CAS  Google Scholar 

  35. Zhao T, Parikh P, Bhashyam S, et al. 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;317:1106–13.

    Article  PubMed  CAS  Google Scholar 

  36. Bose AK, Mocanu MM, Carr RD, et al. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005:54:146–51.

    Article  PubMed  CAS  Google Scholar 

  37. Nikolaidis LA, Doverspike A, Hentosz T, et al. Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 2005;312:303–8.

    Article  PubMed  CAS  Google Scholar 

  38. Nikolaidis LA, Mankad S, Sokos GG, 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.

    Article  PubMed  CAS  Google Scholar 

  39. Balkau B, Picard P, Vol S, et al., for the DESIR Study Group. Consequences of change in waist circumference on cardiometabolic risk factors over 9 years: Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 2007;30:1901–3.

    Article  PubMed  CAS  Google Scholar 

  40. Montague CT, O’Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes 2000;49:883–8.

    Article  PubMed  CAS  Google Scholar 

  41. Libby P. Fat fuels the flame: triglyceride-rich lipoproteins and arterial inflammation. Circ Res 2007;100:299–301.

    Article  PubMed  CAS  Google Scholar 

  42. Fox CS, Pencina MJ, Wilson PW, et al. Lifetime risk of cardiovascular disease among individuals with and without diabetes stratified by obesity status in the Framingham Heart Study. Diabetes Care 2008;31:1582–4.

    Article  PubMed  Google Scholar 

  43. Fox CS, Coady S, Sorlie PD, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham heart study. Circulation 2007;115:1544–50.

    Article  PubMed  Google Scholar 

  44. American Diabetes Association. Complications of diabetes in the United States (verfügbar unter http://schoolwalk.diabetes.org/swfd/swfd_mshs_attach.pdf, Zugriff am 03.12.2009).

  45. Utzschneider KM, Carr DB, Barsness SM, et al. Diet-induced weight loss is associated with an improvement in beta-cell function in older men. J Clin Endocrinol Metab 2004;89:2704–10.

    Article  PubMed  CAS  Google Scholar 

  46. Tuomilehto J, Lindström J, Eriksson JG, et al., Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–50.

    Article  PubMed  CAS  Google Scholar 

  47. Goodpaster BH, Kelley DE, Wing RR, et al. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999;48:839–47.

    Article  PubMed  CAS  Google Scholar 

  48. Markovic TP, Campbell LV, Balasubramanian S, et al. Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes. Diabetes Care 1998;21:695–700.

    Article  PubMed  CAS  Google Scholar 

  49. Wexler R, Feldman D. Initiation of therapy for patients with essential hypertension or comorbid conditions. Prim Care 2006;33:887–901.

    PubMed  Google Scholar 

  50. 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.

    Article  PubMed  CAS  Google Scholar 

  51. Wei Y, Mojsov S. Distribution of GLP-1 and PACAP receptors in human tissues. Acta Physiol Scand 1996;157:355–7.

    Article  PubMed  CAS  Google Scholar 

  52. Nakagawa A, Satake H, Nakabayashi H, et al. Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells. Auton Neurosci 2004;110:36–43.

    Article  PubMed  CAS  Google Scholar 

  53. Yamamoto H, Lee CE, Marcus JN, 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.

    PubMed  CAS  Google Scholar 

  54. Nyström T, Gutniak MK, Zhang Q, 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.

    Article  PubMed  CAS  Google Scholar 

  55. Gros R, You X, Baggio LL, et al. Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 2003;144:2242–52.

    Article  PubMed  CAS  Google Scholar 

  56. Barragan JM, Eng J, Rodriguez R, Blazquez E. Neural contribution to the effect of glucagon-like peptide-1-(7–36) amide on arterial blood pressure in rats. Am J Physiol 1999;277:E784–91.

    PubMed  CAS  Google Scholar 

  57. Noyan-Ashraf MH, Momen MA, Ban K, et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes 2009;58:975–83.

    Article  PubMed  CAS  Google Scholar 

  58. Sulistio M, Carothers C, Mangat M, et al. GLP-1 agonist-based therapies: an emerging new class of antidiabetic drug with potential cardioprotective effects. Curr Atheroscler Rep 2009;11:93–9.

    Article  PubMed  CAS  Google Scholar 

  59. Müssig K, Oncü A, Lindauer P, et al. Effects of intravenous glucagon-like peptide-1 on glucose control and hemodynamics after coronary artery bypass surgery in patients with type 2 diabetes. Am J Cardiol 2008;102:646–7.

    Article  PubMed  CAS  Google Scholar 

  60. Cabou C, Campistron G, Marsollier N, et al. Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity. Diabetes 2008;57:2577–87.

    Article  PubMed  CAS  Google Scholar 

  61. Nikolaidis LA, Elahi D, Hentosz T, et al. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 2004;110:955–61.

    Article  PubMed  CAS  Google Scholar 

  62. Liu H, Hu Y, Simpson RW, Dear AE. Glucagon-like peptide-1 attenuates tumour necrosis factor-alpha-mediated induction of plasmogen activator inhibitor-1 expression. J Endocrinol 2008;196:57–65.

    Article  PubMed  CAS  Google Scholar 

  63. Ruiz-Grande C, Alarcón C, Mérida E, Valverde I. Lipolytic action of glucagon-like peptides in isolated rat adipocytes. Peptides 1992;13:13–6.

    Article  PubMed  CAS  Google Scholar 

  64. Villanueva-Peñacarrillo ML, Márquez L, González N, et al. Effect of GLP-1 on lipid metabolism in human adipocytes. Horm Metab Res 2001;33:73–7.

    Article  PubMed  Google Scholar 

  65. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824–30.

    Article  PubMed  CAS  Google Scholar 

  66. Prigeon RL, Quddusi S, Paty B, D’Alessio DA. Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect. Am J Physiol Endocrinol Metab 2003;285:E701–7.

    PubMed  CAS  Google Scholar 

  67. Sandoval DA, Bagnol D, Woods SC, et al. Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake. Diabetes 2008;57:2046–54.

    Article  PubMed  CAS  Google Scholar 

  68. D’Alessio DA, Prigeon RL, Ensinck JW. Enteral enhancement of glucose disposition by both insulin-dependent and insulin-independent processes. A physiological role of glucagon-like peptide I. Diabetes 1995;44:1433–7.

    Article  PubMed  Google Scholar 

  69. Larsson H, Holst JJ, Ahrén B. Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol Scand 1997;160:413–22.

    Article  PubMed  CAS  Google Scholar 

  70. Eng J, Kleinman WA, Singh L, et al. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992;267:7402–5.

    PubMed  CAS  Google Scholar 

  71. Ghofaili KA, Fung M, Ao Z, et al. Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes. Transplantation 2007;83:24–8.

    Article  PubMed  CAS  Google Scholar 

  72. Mari A, Nielsen LL, Nanayakkara N, et al. Mathematical modeling shows exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea. Horm Metab Res 2006;38:838–44.

    Article  PubMed  CAS  Google Scholar 

  73. Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007;29:139–53.

    Article  PubMed  CAS  Google Scholar 

  74. Timmers L, Henriques JP, de Kleijn DP, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 2009;53:501–10.

    Article  PubMed  CAS  Google Scholar 

  75. Sonne DP, EngstrØm T, Treiman M. Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart. Regul Pept 2008;146:243–9.

    Article  PubMed  CAS  Google Scholar 

  76. Blonde L, Klein EJ, Han J, et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006;8:436–47.

    Article  PubMed  CAS  Google Scholar 

  77. Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008;24:275–86.

    PubMed  CAS  Google Scholar 

  78. Cohen A, Horton E, Gibson H, et al. Effects of exenatide vs insulin glargine on central haemodynamics in subjects with type 2 diabetes. Presented at the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD), Vienna, September 29 to October 2, 2009:abstract 757.

  79. Horton ES, Cohen A, Gibson H, et al. Effects of exenatide vs insulin glargine on cardiovascular risk factors in subjects with type 2 diabetes. Presented at the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD), Vienna, September 29 to October 2, 2009:abstract 760.

  80. Bergenstal R. Exenatide once weekly improved cardiometabolic risk factors in subjects with type 2 diabetes during once year of treatment. Presented at the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD), Vienna, September 29 to October 2, 2009:abstract 758.

  81. VilsbØll T, Zdravkovic M, Le-Thi T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007;30:1608–10.

    Article  PubMed  CAS  Google Scholar 

  82. Agerso H, Jensen LB, Elbrond B, et al. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 2002;45:195–202.

    Article  PubMed  CAS  Google Scholar 

  83. Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000;43:1664–9.

    Article  PubMed  CAS  Google Scholar 

  84. Jendle J, Nauck M, Matthews D, et al., for the LEAD-2 and LEAD-2 Study Groups. Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of reduction in fat tissue. Diabetes Obes Metab 2009;11:1162–72.

    Article  CAS  Google Scholar 

  85. Colagiuri S, Frid A, Zdravkovic M, et al. The once-daily human glucagon-like peptide-1 analog liraglutide reduces systolic blood pressure in patients with type 2 diabetes. Presented at the American Diabetes Association (ADA) 68th Annual Scientific Sessions, San Francisco, CA, June 6–10, 2008:abstract 554.

  86. Plutzky J, Garber A, Toft AD, Poulter NR. Meta-analysis demonstrates that liraglutide, a once-daily human GLP-1 analogue, significantly reduces lipids and other markers of cardiovascular risk in type 2 diabetes. Presented at the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD), Vienna, September 29 to October 2, 2009:abstract 762.

  87. 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.

    Article  PubMed  CAS  Google Scholar 

  88. Courrèges JP, VilsbØll T, Zdravkovic M, et al. Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with type 2 diabetes. Diabet Med 2008;25:1129–31.

    Article  PubMed  Google Scholar 

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  1. Medizinische Klinik IV, Universitätsklinikum Tübingen, Tübingen, Germany

    Baptist Gallwitz

  2. Medizinische Klinik IV, Universitätsklinikum Tübingen, Otfried-Müller-Straße 10, 72076, Tübingen, Germany

    Baptist Gallwitz

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Gallwitz, B. Inkretine: Gibt es kardiovaskuläre Effekte?. Herz 35, 130–138 (2010). https://doi.org/10.1007/s00059-010-3333-3

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