Skip to main content
Log in

Treatment of patients with diabetes with GLP-1 analogues or DPP-4- inhibitors: a hot topic for cardiologists?

  • CRITICAL PERSPECTIVE
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Novel drugs for the treatment of patients with diabetes are of interest for cardiologists if they reduce the risk of cardiovascular events. However, as documented by the current discussion about the potential benefits of glitazones, high hopes can fail. Initial beneficial cardiovascular effects shown in proof-of-concept studies were muted by the apparent higher mortality in the metaanalysis of studies with rosiglitazone. Having this in mind, how should one judge about new, emerging antidiabetic therapies, in particular those influencing the incretin axis? The rapidly increasing use of GLP-1 analogues and DPP-4 inhibitors for the treatment of type 2 diabetes mellitus may be of major interest for the cardiologist. Potential beneficial actions on the cardiovascular system so far shown in animal experiments and small proof of concept studies may provide the rationale for using these drugs specifically in diabetic patients with secondary complications such as macrovascular disease or diabetic cardiomyopathy. Theoretically, these new therapies could also proof beneficial in patients with heart failure, independently of concomittend diabetes mellitus. However, many unanswered questions need to be addressed in the near future to extend the experimental findings to potential benefits of real life patients. In summary a new class of antidiabetic drugs, which could possibly directly influence cardiovascular effects of diabetes mellitus and thus possibly treat or even prevent life threatening complications has become available. Further studies both assessing surrogate parameters as well as hard endpoint studies are needed to support the hypothesis generated from the summarized experimental studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Amori RE, Lau J, Pittas AG (2007) Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 298:194–206

    Article  PubMed  CAS  Google Scholar 

  2. Ban K, Noyan-Ashraf MH, Hoefer J et al (2008) 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

    Article  PubMed  CAS  Google Scholar 

  3. Barragan JM, Rodriguez RE, Blazquez E (1994) 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

    PubMed  CAS  Google Scholar 

  4. Barragan JM, Rodriguez RE, Eng J et al (1996) 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

    Article  PubMed  CAS  Google Scholar 

  5. Basu A, Charkoudian N, Schrage W et al (2007) 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

    Article  PubMed  CAS  Google Scholar 

  6. Bose AK, Mocanu MM, Carr RD et al (2005) Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 54:146–151

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Buse JB, Klonoff DC, Nielsen LL et al (2007) 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 29:139–153

    Article  PubMed  CAS  Google Scholar 

  9. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705.

    Article  PubMed  CAS  Google Scholar 

  10. Golpon HA, Puechner A, Welte T et al (2001) Vasorelaxant effect of glucagon-like peptide-(7-36)amide and amylin on the pulmonary circulation of the rat. Regul Pept 102:81–86

    Article  PubMed  CAS  Google Scholar 

  11. Gros R, You X, Baggio LL et al (2003) Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 144:2242–2252

    Article  PubMed  CAS  Google Scholar 

  12. Inzucchi SE, McGuire DK (2008) New drugs for the treatment of diabetes: part II: incretin-based therapy and beyond. Circulation 117:574–584

    Article  PubMed  Google Scholar 

  13. Kavianipour M, Ehlers MR, Malmberg K et al (2003) Glucagon-like peptide-1 (7-36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium. Peptides 24:569–578

    Article  PubMed  CAS  Google Scholar 

  14. Klonoff DC, Buse JB, Nielsen LL et al (2008) 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

    Article  PubMed  CAS  Google Scholar 

  15. Lankisch M, Futh R, Schotes D et al (2006) High prevalence of undiagnosed impaired glucose regulation and diabetes mellitus in patients scheduled for an elective coronary angiography. Clin Res Cardiol 95:80–87

    Article  PubMed  CAS  Google Scholar 

  16. Lankisch M, Futh R, Gulker H et al (2008) Screening for undiagnosed diabetes in patients with acute myocardial infarction. Clin Res Cardiol 97(10):753–759

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Nikolaidis LA, Elahi D, Hentosz T et al (2004) 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

    Article  PubMed  CAS  Google Scholar 

  19. Norhammar A, Tenerz A, Nilsson G et al (2002) Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 359:2140–2144

    Article  PubMed  CAS  Google Scholar 

  20. Nystrom T, Gutniak MK, Zhang Q et al (2004) 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

    Article  PubMed  Google Scholar 

  21. Richter G, Feddersen O, Wagner U et al (1993) GLP-1 stimulates secretion of macromolecules from airways and relaxes pulmonary artery. Am J Physiol 265:L374-L381

    PubMed  CAS  Google Scholar 

  22. Saraceni C, Broderick TL (2007) Effects of glucagon-like peptide-1 and long-acting analogues on cardiovascular and metabolic function. Drugs R D 8:145–153

    Article  PubMed  CAS  Google Scholar 

  23. Schnell O (2006) Glucose control in cardiac disease. Clin Res Cardiol 951:i70–i73

    Article  Google Scholar 

  24. Sokos GG, Nikolaidis LA, Mankad S et al (2006) 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

    Article  PubMed  CAS  Google Scholar 

  25. Taegtmeyer H (2004) Cardiac metabolism as a target for the treatment of heart failure. Circulation 110:894–896

    Article  PubMed  Google Scholar 

  26. Taegtmeyer H, McNulty P, Young ME (2002) Adaption and maladaption of the heart in diabetes: part 1. Circulation 105:1727–1733

    Article  PubMed  CAS  Google Scholar 

  27. Thrainsdottir I, Malmberg K, Olsson A et al (2004) 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 1:40–43

    Article  PubMed  Google Scholar 

  28. Vila Petroff MG, Egan JM, Wang X et al (2001) Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res 89:445–452

    Article  PubMed  CAS  Google Scholar 

  29. Wei Y, Mojsov S (1996) Distribution of GLP-1 and PACAP receptors in human tissues. Acta Physiol Scand 157:355–357

    Article  PubMed  CAS  Google Scholar 

  30. Yu M, Moreno C, Hoagland KM et al (2003) Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens 21:1125–1135

    Article  PubMed  CAS  Google Scholar 

  31. Zhao T, Parikh P, Bhashyam S et al (2006) 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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Jax.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jax, T. Treatment of patients with diabetes with GLP-1 analogues or DPP-4- inhibitors: a hot topic for cardiologists?. Clin Res Cardiol 98, 75–79 (2009). https://doi.org/10.1007/s00392-008-0725-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-008-0725-y

Keywords

Navigation