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Theme: Diabetes, Obesity & Metabolic Syndrome - Review

Potential cardiovascular effects of incretin-based therapies

&
Pages 337-351 | Published online: 10 Jan 2014

References

  • Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in Type II diabetic patients and in healthy subjects. Diabetes44, 1126–1131 (1995).
  • Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for Type 2 diabetes. Diabetes47, 1663–1670 (1998).
  • Haffner SM, Lehto S, Ronnemaa T, Pyorala 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.339, 229–234 (1998).
  • 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.358, 219–224 (1995).
  • Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology137, 2968–2978 (1996).
  • Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology132, 2131–2157 (2007).
  • 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. Circulation117, 2340–2350 (2008).
  • Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM. Glucagon-like peptide 1 can directly protect the heart against ischemia–reperfusion injury. Diabetes54, 146–151 (2005).
  • Bose AK, Mocanu MM, Carr RD, Yellon DM. Myocardial ischaemia–reperfusion injury is attenuated by intact glucagon like peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway. Cardiovasc. Drugs Ther.21, 253–256 (2007).
  • Hausenloy DJ, Yellon DM. New directions for protecting the heart against ischaemia–reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res.61, 448–460 (2004).
  • 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.287, e1209–e1215 (2004).
  • Usdin TB, Mezey E, Button DC, Brownstein MJ, Bonner TI. Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Endocrinology133, 2861–2870 (1993).
  • Zhong Q, Bollag RJ, Dransfield DT et al. Glucose-dependent insulinotropic peptide signaling pathways in endothelial cells. Peptides21, 1427–1432 (2000).
  • Bose AK, Mocanu MM, Carr RD, Yellon DM. Glucagon like peptide-1 is protective against myocardial ischemia–reperfusion injury when given either as a preconditioning mimetic or at reperfusion in an isolated rat heart model. Cardiovasc. Drugs Ther.19, 9–11 (2005).
  • 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.146, 243–249 (2008).
  • Noyan-Ashraf MH, Momen MA, Ban K et al. The GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes following experimental myocardial infarction in mice. Diabetes58, 975–983 (2009).
  • Bao W, Aravindhan K, Alsaid H et al. Albiglutide, a long lasting glucagon-like peptide-1 analog, protects the rat heart against ischemia–reperfusion injury: evidence for improving cardiac metabolic efficiency. PLoS One6, e23570 (2010).
  • Sauvé M, Ban K, Momen MA et al. Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice. Diabetes59, 1063–1073 (2010).
  • Hausenloy DJ, Wynne AM, Theodorou L, Mocanu MM, Yellon DM. Dipeptidyl peptidase IV inhibitors limit myocardial infarct size in a glucose-sensitive manner. Heart96, e11 (2010) (Abstract FC1).
  • 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.317, 1106–1113 (2006).
  • Ravassa S, Zudaire A, Carr RD, Díez J. Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol.300, H1361–H1372 (2011).
  • Lenski M, Kazakov A, Marx N, Böhm M, Laufs U. Effects of DPP-4 inhibition on cardiac metabolism and function in mice. J. Mol. Cell Cardiol.51, 906–918 (2011).
  • Belke DD, Larsen TS, Gibbs EM, Severson DL. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am. J. Physiol. Endocrinol. Metab.279, E1104–E1113 (2000).
  • Dokken BB, La Bonte LR, Davis-Gorman G, Teachey MK, Seaver N, McDonagh PF. Glucagon-like peptide-1 (GLP-1), immediately prior to reperfusion, decreases neutrophil activation and reduces myocardial infarct size in rodents. Horm. Metab. Res.43, 300–305 (2011).
  • Ban K, Kim KH, Cho CK et al. 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. Endocrinology151, 1520–1531 (2010).
  • 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.312, 303–308 (2005).
  • Kavianipour M, Ehlers MR, Malmberg K et al. Glucagon-like peptide-1 (7–36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium. Peptides24, 569–578 (2003).
  • Kristensen J, Mortensen UM, Schmidt M, Nielsen PH, Nielsen TT, Maeng M. Lack of cardioprotection from subcutaneously and preischemic administered liraglutide in a closed chest porcine ischemia reperfusion model. BMC Cardiovasc. Disord.9, 31 (2009).
  • 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.53, 501–510 (2009).
  • 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. Circulation109, 962–965 (2004).
  • 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 doi:10.1136/hrt.2010.219345 (2011) (Epub ahead of print).
  • 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. Imaging3, 195–201 (2010).
  • Read PA, Hoole SP, White PA et al. A pilot study to assess whether glucagon-like peptide-1 protects the heart from ischemic dysfunction and attenuates stunning after coronary balloon occlusion in humans. Circ. Cardiovasc. Interv.4, 266–272 (2011).
  • 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.100, 824–829 (2007).
  • 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.102, 646–647 (2008).
  • Lønborg J, Vejlstrup N, Kelbæk H et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur. Heart J. doi:10.1093/eurheartj/ehr309 (2011) (Epub ahead of print).
  • Poornima I, Brown SB, Bhashyam S, Parikh P, Bolukoglu H, Shannon RP. Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat. Circ. Heart Fail.1, 153–160 (2008).
  • Vyas AK, Yang KC, Woo D et al. Exenatide improves glucose homeostasis and prolongs survival in a murine model of dilated cardiomyopathy. PLoS One6, e17178 (2011).
  • Liu Q, Anderson C, Broyde A et al. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure. Cardiovasc. Diabetol.9, 76 (2010).
  • 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. Circulation110, 955–961 (2004).
  • Nikolaidis LA, Elahi D, Shen YT, Shannon RP. Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol.289, H2401–H2408 (2005).
  • Bhashyam S, Fields AV, Patterson B et al. Glucagon-like peptide-1 increases myocardial glucose uptake via p38alpha MAP kinase-mediated, nitric oxide-dependent mechanisms in conscious dogs with dilated cardiomyopathy. Circ. Heart Fail.3, 512–521 (2010).
  • Gomez N, Touihri K, Matheeussen V et al. Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure. Eur. J. Heart Fail.14, 14–21 (2012).
  • 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.12, 694–699 (2006).
  • Halbirk M, Nørrelund H, Møller N 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.298, H1096–H1102 (2010).
  • Nyström T, Gonon AT, Sjöholm A, Pernow J. Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul. Pept.125, 173–177 (2005).
  • Nathanson D, Erdogdu O, Pernow J, Zhang Q, Nyström T. Endothelial dysfunction induced by triglycerides is not restored by exenatide in rat conduit arteries ex vivo. Regul. Pept.157, 8–13 (2009).
  • Gaspari T, Liu H, Welungoda I et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model. Diab. Vasc. Dis. Res.8, 117–124 (2011).
  • Doran AC, Meller N, McNamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler. Thromb. Vasc. Biol.28, 812–819 (2008).
  • Vanhoutte PM. Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ. J.73, 595–601 (2009).
  • Arakawa M, Mita T, Azuma K et al. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes59, 1030–1037 (2010).
  • Goto H, Nomiyama T, Mita T et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury. Biochem. Biophys. Res. Commun.405, 79–84 (2011).
  • Murthy SN, Hilaire RC, Casey DB et al. The synthetic GLP-I receptor agonist, exenatide, reduces intimal hyperplasia in insulin resistant rats. Diab. Vasc. Dis. Res.7, 138–144 (2010).
  • 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.391, 1405–1408 (2010).
  • 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.201, 59–66 (2009).
  • Hattori Y, Jojima T, Tomizawa A et al. A glucagon-like peptide-1 (GLP-1) analogue, liraglutide, upregulates nitric oxide production and exerts anti-inflammatory action in endothelial cells. Diabetologia53, 2256–2263 (2010).
  • Nagashima M, Watanabe T, Terasaki M et al. Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice. Diabetologia54, 2649–2659 (2011).
  • 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.58, 157–166 (2011).
  • Shah Z, Kampfrath T, Deiuliis JA et al. Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation124, 2338–2349 (2011).
  • 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.293, E1289–E1295 (2007).
  • 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 Care34, 697–702 (2011).
  • 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 Care33, 1028–1030 (2010).
  • Lundkvist J, Berne C, Bolinder B, Jönsson L. The economic and quality of life impact of hypoglycemia. Eur. J. Health Econ.6, 197–202 (2005).
  • Chico A, Vidal-Ríos P, Subirà M, Novials A. The continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with Type 1 and Type 2 diabetes but is not better than frequent capillary glucose measurements for improving metabolic control. Diabetes Care26, 1153–1157 (2003).
  • Cryer PE. Hypoglycemia: still the limiting factor in the glycemic management of diabetes. Endocr. Pract.14, 750–756 (2008).
  • Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care33, 1389–1394 (2010).
  • Bonds DE, Miller ME, Bergenstal RM et al. The association between symptomatic, severe hypoglycaemia and mortality in Type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ340, b4909 (2010).
  • Yakubovich N, Gerstein HC. Serious cardiovascular outcomes in diabetes: the role of hypoglycemia. Circulation123, 342–348 (2011).
  • Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with Type 2 diabetes. Diabetes Care34, 1164–1170 (2011).
  • Madsbad S, Krarup T, Deacon CF, Holst JJ. Glucagon-like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials. Curr. Opin. Clin. Nutr. Metab. Care11, 491–499 (2008).
  • Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in Type 2 diabetes. JAMA303, 1410–1418 (2010).
  • Flynn C, Bakris GL. Blood pressure targets for patients with diabetes or kidney disease. Curr. Hypertens. Rep.13, 452–455 (2011).
  • 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.266, E459–E466 (1994).
  • Barragán JM, Rodríguez RE, Eng J, Blázquez E. Interactions of exendin-(9–39) with the effects of glucagon-like peptide-1-(7–36) amide and of exendin-4 on arterial blood pressure and heart rate in rats. Regul. Pept.67, 63–68 (1996).
  • Yu M, Moreno C, Hoagland KM et al. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J. Hypertens.21, 1125–1135 (2003).
  • Hirata K, Kume S, Araki S et al. Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochem. Biophys. Res. Commun.380, 44–49 (2009).
  • 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 Care33, 1759–1765 (2010).
  • Mistry GC, Maes AL, Lasseter KC et al. Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension. J. Clin. Pharmacol.48, 592–598 (2008).
  • Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with Type 2 diabetes. Am. J. Hypertens.23, 334–339 (2010).
  • Gill A, Hoogwerf BJ, Burger J et al. Effect of exenatide on heart rate and blood pressure in subjects with Type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study. Cardiovasc. Diabetol.9, 6 (2010).
  • Gallwitz B, Vaag A, Falahati A, Madsbad S. Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time. Int. J. Clin. Pract.64, 267–276 (2009).
  • Pratley RE, Nauck M, Bailey T et al. Liraglutide versus sitagliptin for patients with Type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet375, 1447–1456 (2010).
  • Pinelli NR, Hurren KM. Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonists compared with exenatide twice daily and sitagliptin in type 2 diabetes mellitus: a systematic review and meta-analysis. Ann. Pharmacother.45, 850–860 (2011).
  • Edwards CM, Edwards AV, Bloom SR. Cardiovascular and pancreatic endocrine responses to glucagon-like peptide-1(7–36) amide in the conscious calf. Exp. Physiol.82, 709–716 (1997).
  • Buse JB, Rosenstock J, Sesti G et al. 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). Lancet374, 39–47 (2009).
  • Blevins T, Pullman J, Malloy J et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with Type 2 diabetes. J. Clin. Endocrinol. Metab.96, 1301–1310 (2011).
  • Griffioen KJ, Wan R, Okun E et al. GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons. Cardiovasc. Res.89, 72–78 (2011).
  • Gustavson SM, Chen D, Somayaji V et al. Effects of a long-acting GLP-1 mimetic (PF-04603629) on pulse rate and diastolic blood pressure in patients with Type 2 diabetes mellitus. Diabetes Obes. Metab.13, 1056–1058 (2011).
  • Fox K, Borer JS, Camm AJ et al. Resting heart rate in cardiovascular disease. J. Am. Coll. Cardiol.50, 823–830 (2007).
  • Verdich C, Flint A, Gutzwiller JP et al. A meta-analysis of the effect of glucagon-like peptide-1 (7–36) amide on ad libitum energy intake in humans. J. Clin. Endocrinol. Metab.86, 4382–4389 (2001).
  • 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. Lancet359, 824–830 (2002).
  • Kanoski SE, Fortin SM, Arnold M, Grill HJ, Hayes MR. Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4. Endocrinology152, 3103–3112 (2011).
  • Orskov 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. Diabetes45, 832–935 (1996).
  • Harder H, Nielsen L, Tu DT, Astrup A. The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes. Diabetes Care27, 1915–1921 (2004).
  • Jendle J, Nauck MA, Matthews DR et al. 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 a reduction in fat tissue. Diabetes Obes. Metab.11, 1163–1172 (2009).
  • Bunck MC, Diamant M, Eliasson B et al. Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care33, 1734–1737 (2010).
  • 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.24, 275–286 (2008).
  • Edwards CM, Stanley SA, Davis R et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am. J. Physiol. Endocrinol. Metab.281, E155–E161 (2001).
  • Pinelli NR, Jantz A, Smith Z et al. Effect of administration time of exenatide on satiety responses, blood glucose, and adverse events in healthy volunteers. J. Clin. Pharmacol.51, 165–172 (2011).
  • Sze L, Purtell L, Jenkins A et al. Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader–Willi syndrome. J. Clin. Endocrinol. Metab.96, E1314–E1319 (2011).
  • Garber A, Henry R, Ratner R et al. Liraglutide versus glimepiride monotherapy for Type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, Phase III, double-blind, parallel-treatment trial. Lancet373, 473–481 (2009).
  • Holst JJ, Deacon CF, Vilsbøll T, Krarup T, Madsbad S. Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol. Med.14, 161–168 (2008).
  • Esposito K, Cozzolino D, Bellastella G et al. Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in Type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes. Metab.13, 594–603 (2011).
  • Ansar S, Koska J, Reaven PD. Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins. Cardiovasc. Diabetol.10, 61 (2011).
  • Meier JJ, Gethmann A, Götze O et al. Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia49, 452–458 (2006).
  • Matikainen N, Mänttäri S, Schweizer A et al. Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with Type 2 diabetes. Diabetologia49, 2049–2057 (2006).
  • 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. Atherosclerosis212, 217–222 (2010).
  • Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P. Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with Type 2 diabetes. Diabetes Obes. Metab.13, 366–373 (2011).
  • Hsieh J, Longuet C, Baker CL et al. The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice. Diabetologia53, 552–561 (2010).
  • Derosa G, Maffioli P, Salvadeo SA et al. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled Type 2 diabetes mellitus patients. Metabolism59, 887–895 (2010).
  • Derosa G, Maffioli P, Ferrari I et al. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled Type 2 diabetic patients. Horm. Metab. Res.42, 663–669 (2010).
  • 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.25, 1129–1131 (2008).
  • Bethel MA, Green J, Califf RM, Holman RR. Rationale and design of the trial evaluating cardiovascular outcomes with sitagliptin (TECOS). Diabetes58(Suppl. 1), A555 (2009) (Abstract 2152-PO).
  • White WB, Bakris GL, Bergenstal RM et al. Examination of Cardiovascular Outcomes with Alogliptin versus 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.162, 620–626.e1 (2011).
  • Scirica BM, Bhatt DL, Braunwald E 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.162(5), 818–825.e6 (2011).
  • Rosenstock J, Marx N, Kahn SE et al. The rationale and design of the CAROLINA trial: an Active Comparator Cardiovascular Outcome Study of the DPP-4 Inhibitor Linagliptin in Patients with Type 2 Diabetes at High Cardiovascular Risk. Diabetes60(Suppl. 1), A303 (2011) (Abstract 1103-P).
  • Williams-Herman D, Engel SS, Round E et al. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with Type 2 diabetes. BMC. Endocr. Disord.10, 7 (2010).
  • Schweizer A, Dejager S, Foley JE, Couturier A, Ligueros-Saylan M, Kothny W. Assessing the cardio–cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III Type 2 diabetes population. Diabetes Obes. Metab.12, 485–494 (2010).
  • White WB, Gorelick PB, Fleck P, Smith N, Wilson C, Pratley R. Cardiovascular events in patients receiving alogliptin: a pooled analysis of randomized clinical trials. Diabetes59(Suppl. 1), A105 (2010) (Abstract 391-PP).
  • Frederich R, Alexander JH, Fiedorek FT et al. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for Type 2 diabetes. Postgrad. Med.122, 16–27 (2010).
  • 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.10, 22 (2011).
  • Marso SP, Lindsey JB, Stolker JM et al. Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of Phase 2: 3 liraglutide clinical development studies. Diab. Vasc. Dis. Res.8, 237–240 (2011).
  • Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with Type 2 diabetes mellitus: a prespecified, prospective, and adjudicated meta-analysis of a Phase 3 programme. Cardiovasc. Diabetol.11, 3 (2012).
  • Monami M, Cremasco F, Lamanna C et al. Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Exp. Diabetes Res.2011, 215764 (2011).
  • Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr. Med. Res. Opin.27, 57–64 (2011).
  • Best JH, Hoogwerf BJ, Herman WH et al. Risk of cardiovascular disease events in patients withType 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 Care34, 90–95 (2011).
  • Best JH, Little W, Chiquette E, Saunders WB. The risk of heart failure among patients receiving exenatide versus other glucose-lowering medications for Type 2 diabetes: a matched retrospective cohort analysis of the GE healthcare electronic medical record database. Diabetes60(Suppl. 1), A311 (2011) (Abstract 1133-P).
  • Nathan DM, Cleary PA, Backlund JY et al. Intensive diabetes treatment and cardiovascular disease in patients with Type 1 diabetes. N. Engl. J. Med.353, 2643–5326 (2005).
  • Gerstein HC, Miller ME, Byington RP et al. Effects of intensive glucose lowering in Type 2 diabetes. N. Engl. J. Med.358, 2545–2559 (2008).
  • Patel A, MacMahon S, Chalmers J et al. Intensive blood glucose control and vascular outcomes in patients with Type 2 diabetes. N. Engl. J. Med.358, 2560–2572 (2008).
  • Duckworth W, Abraira C, Moritz T et al. Glucose control and vascular complications in veterans with Type 2 diabetes. N. Engl. J. Med.360, 129–139 (2009).
  • Treiman M, Elvekjaer M, Engstrøm T, Jensen JS. Glucagon-like peptide 1 – a cardiologic dimension. Trends Cardiovasc. Med.20, 8–12 (2010).
  • Fadini GP, Boscaro E, Albiero M 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 Care33, 1607–1609 (2010).
  • Kanki S, Segers VF, Wu W et al. Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium. Circ. Heart Fail.4, 509–518 (2011).
  • Scholte M, Timmers L, Bernink FJ et al. Effect of additional treatment with exenatide in patients with an acute myocardial infarction (EXAMI): study protocol for a randomized controlled trial. Trials12, 240 (2011).
  • Hausenloy DJ, Yellon DM. Taking lizard saliva to heart. Eur. Heart J. doi:10.1093/eurheartj/ehr382 (2011) (Epub ahead of print).

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