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Effects of incretin-based therapy in patients with heart failure and myocardial infarction

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Abstract

Studies designed to evaluate the short-term effects of incretin-related drugs in subjects with cardiac disease are still preliminary. In patients with heart failure, two of five studies showed that glucagon-like peptide-1 (GLP-1) infusion was associated with an absolute increase in left ventricular ejection fraction (LVEF) by 6–10 %, whereas no significant benefit was observed in the remaining three studies. In patients with coronary artery disease, single infusion of the GLP-1 receptor analog, exenatide, did not increase LVEF, but this drug may decrease infarct size in patients with myocardial infarction presenting with short duration of ischemic symptoms. Single dose of GLP-1 and the dipeptidyl-peptidase-IV (DPP-IV) inhibitor, sitagliptin, may improve left ventricular function, predominantly in ischemic segments, and attenuate post-ischemic stunning. Nausea, vomiting and hypoglycemia were the most common adverse effects associated with GLP-1 and exenatide administration. Increased heart rate was also observed with exenatide in patients with heart failure. Large randomized trials including diabetic patients with preexisting heart failure and myocardial infarction showed that chronic therapy with the DPP-IV inhibitors saxagliptin and alogliptin did not reduce cardiovascular events or mortality. Moreover, saxagliptin use was associated with significant increase in frequency of heart failure requiring hospitalization, hypoglycemia and angioedema. Overall, short-term preliminary data suggest potential cardioprotective effects of exenatide and sitagliptin in patients with heart failure and myocardial infarction. Meanwhile, long-term randomized trials suggest no benefit of alogliptin, and increased harm associated with the use of saxagliptin.

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References

  1. N. Mikhail, Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of type 2 diabetes. Expert Opin. Investig. Drugs 17, 845–853 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. L.A. Nikolaidis, D. Elahi, T. Hentosz 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 110, 955–961 (2004)

    Article  CAS  PubMed  Google Scholar 

  3. I. Poornima, S.B. Brown, S. Bhashyam et al., 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)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Y. Wei, S. Mojsov, Tissue-specific expression of the human receptor for glucagon-like peptide 1: brain, heart, and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 358, 219–224 (1995)

    Article  CAS  PubMed  Google Scholar 

  5. T. Nystrom, M.K. Gutniak, Q. Zhang 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)

    Article  PubMed  Google Scholar 

  6. I. Thrainsdottir, K. Malberg, A. Olsson et al., Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diabetes Vasc. Dis. Res. 1, 40–43 (2004)

    Article  Google Scholar 

  7. L.A. Nikolaidis, S. Mankad, G. Sokos et al., Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 109, 962–965 (2004)

    Article  CAS  PubMed  Google Scholar 

  8. G.G. Sokos, L.A. Nikolaidis, S. Mankad et al., Glucagon-like peptide infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J. Card. Fail. 12, 694–699 (2006)

    Article  CAS  PubMed  Google Scholar 

  9. M. Halbirk, H. Norrelund, N. Moller 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)

    Article  CAS  PubMed  Google Scholar 

  10. D. Nathanson, B. Ullman, U. Lofstrom et al., 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 55, 926–935 (2012)

    Article  CAS  PubMed  Google Scholar 

  11. G.G. Sokos, H. Bolukoglu, J. German 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)

    Article  CAS  PubMed  Google Scholar 

  12. K. Mussig, A. Oncu, P. Lindauer 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)

    Article  PubMed  Google Scholar 

  13. P.A. Read, F.Z. Khan, D.P. Dutka, Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart 98, 408–413 (2012)

    Article  CAS  PubMed  Google Scholar 

  14. J. Lonborg, N. VejIstrup, H. Kelbaek et al., Exenatide reduces reperfusion injury bin patients with ST-segment elevation myocardial infarction. Eur. Heart J. 33, 1491–1499 (2012)

    Article  CAS  PubMed  Google Scholar 

  15. J. Lonborg, H. Kelbaek, N. Veilstrup et al., Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ. Cardiovasc. Interv. 5, 288–295 (2012)

    Article  PubMed  Google Scholar 

  16. F.J.P. Bernink, L. Timmers, M. Diamant et al., Effect of additional treatment with Exenatide in patients with an acute myocardial Infarction: the EXAMI study. Int. J. Cardiol. 167, 289–290 (2013)

    Article  PubMed  Google Scholar 

  17. J.S. Woo, W. Kim, S.J. Ha et al., 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. 33, 2252–2260 (2013)

    Article  CAS  PubMed  Google Scholar 

  18. P.A. Read, F.Z. Kahn, P.M. Heck et al., DPP-4 inhibtion 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 3, 195–201 (2012)

    Article  Google Scholar 

  19. R.J. Burns, R.J. Gibbons, Q. Yi et al., The relationship of left ventricular ejection fraction, end-systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction. J. Am. Coll. Cardiol. 39, 30–36 (2002)

    Article  PubMed  Google Scholar 

  20. M. Gejl, H.M. Sondergaard, C. Stecher et al., Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 97, E1165–E1169 (2012)

    Article  CAS  PubMed  Google Scholar 

  21. C. Irace, S. De Luca, E. Shehaj et al., Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: results from an observational research. Diabetes Vasc. Dis. Res. 10, 72–77 (2013)

    Article  Google Scholar 

  22. R. Nielsen, H. Wiggers, M. Halbirk et al., Metabolic effects of short-term GLP-1 treatment in insulin resistant heart failure patients. Expert Clin. Endocrinol. Diabetes 120, 266–272 (2012)

    Article  CAS  Google Scholar 

  23. K. Ban, H. Noyan-Ashraf, J. Hoefer 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 117, 2340–2350 (2008)

    Article  CAS  PubMed  Google Scholar 

  24. L.E. Robinson, T.A. Holt, K. Rees et al., Effects of exenatide and liraglutide on heart rate, blood pressure, and body weight: systematic review and meta-analysis. Br. Med. J. Open Access 3, 1–13 (2013)

    Google Scholar 

  25. K. Fox, I. Ford, P. Gabriel Steg et al., Heart rate as a prognostic factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 372, 817–821 (2008)

    Article  PubMed  Google Scholar 

  26. B.M. Scirica, D.L. Bhatt, E. Braunwald et al., for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369, 1317–1326 (2013)

    Article  CAS  PubMed  Google Scholar 

  27. W.B. White, C.P. Cannon, S.R. Heller et al., for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369, 1327–1335 (2013)

    Article  CAS  PubMed  Google Scholar 

  28. S.K. Majumdar, S.E. Inzucchi, Investigational anti-hyperglycemic agents: the future of type 2 diabetes therapy? Endocrine 44, 47–58 (2013)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The author thanks the librarian Irene Lovas, MLS, for her expert help with the literature review.

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Authors and Affiliations

  1. Endocrinology Division, OliveView-UCLA Medical Center, David-Geffen School of Medicine, 14445 Olive View Dr, Sylmar, 91342, CA, USA

    Nasser Mikhail

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  1. Nasser Mikhail
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Correspondence to Nasser Mikhail.

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Mikhail, N. Effects of incretin-based therapy in patients with heart failure and myocardial infarction. Endocrine 47, 21–28 (2014). https://doi.org/10.1007/s12020-014-0175-4

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  • DOI: https://doi.org/10.1007/s12020-014-0175-4

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