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Treatment of type 2 diabetes mellitus with GLP-1 antagonists


Authors: M. Haluzík;  M. Urbanová;  P. Trachta
Authors‘ workplace: III. interní klinika 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA
Published in: Vnitř Lék 2011; 57(4): 411-415
Category: 12th national Symposium diabetes, "Diabetes and Gastroenterology", Hradec Kralove, 4 to 5 June 2010

Overview

Increased prevalence of type 2 diabetes mellitus and its close clustering with obesity, arterial hypertension, dyslipidemia and other pathologies commonly referred to as metabolic or insulin resistance syndrome, represents one of the major health problem worldwide. The side effects of most of oral antidiabetics and insulin include increase in body weight and/or hypoglycemia that may limit its use in some patients. GLP-1 agonists are medicaments stimulating GLP-1 receptor similarly as endogenous GLP-1. These substances are in contrast to endogenous GLP-1 resistant to inactivation by ubiquitous enzyme dipeptidyl-peptidase 4 which enables its administration once or twice daily. GLP-1 agonists not only significantly improve diabetes compensation with minimal risk of hypoglycemia but also decrease body weight, blood pressure and improve numerous parameters of cardiovascular risk. The aim of this review is to summarize current knowledge with respect to use of GLP-1 agonists in the treatment of type 2 diabetes and its future perspectives. We will focus mostly on the two drugs that are currently available in Czech Republic – exenatide and liraglutide.

Key words:
type 2 diabetes mellitus – obesity – GLP-1 agonists – cardiovascular complications


Sources

1. Haffner SM, Lehto S, Rönnemaa T et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Eng J Med 1998; 339: 229–234.

2. Haffner SM. Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol 2003; 92: 18J–26J.

3. Reaven G. Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease. Circulation 2002; 106: 286–288.

4. Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Dia­betes Res Clin Pract 2003; 61 (Suppl 1): S9–S18.

5. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000; 106: 171–176.

6. 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–E206.

7. Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest 2007; 117: 24–32.

8. Drucker DJ. The biology of incretin hormones. Cell Metab 2006; 3: 153–165.

9. Drucker DJ. Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action. Diabetes Care 2007; 30: 1335–1343.

10. Nauck MA. Glucagon-like peptide 1 (GLP-1) in the treatment of diabetes. Hormone and metabolic research 2004; 36: 852–858.

11. Drucker DJ, Sherman SI, Gorelick FS et al. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care 2010; 33: 428–433.

12. Cervera A, Wajcberg E, Sriwijitkamol A et al. Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. Am J Physiol Endorinol Metab 2008; 294: E846–E852.

13. 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: 1092–1100.

14. Buse JB, Henry RR, Han J et al. 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: 2628–2635.

15. 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: 275–286.

16. Nauck MA, Duran S, Kim D et al. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 2007; 50: 259–267.

17. Heine RJ, Van Gaal LF, Johns D et al. GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2005; 143: 559–569.

18. Drucker DJ, Buse JB, Taylor K et al. DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008; 372: 1240–1250.

19. Diamant M, Van Gaal L, Stranks S et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 2010; 375: 2234–2243.

20. Drucker DJ, Dritselis A, Kirkpatrick P. Liraglutide. Nat Rev Drug Discov 2010; 9: 267–268.

21. 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: 1224–1230.

22. Doggrell SA. Is liraglutide or exenatide better in type 2 diabetes? Expert Opin Pharmacother 2009; 10: 2769–2772.

23. 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). Lancet 2009; 374: 39–47.

24. 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: 2943–2952.

25. Pratley RE, Nauck M, Bailey T et al. 1860-LIRA-DPP-4 Study Group. 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. Lancet 2010; 375: 1447–1456.

26. Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics) – preclinical and clinical results. Best Pract Res Clin Endocrinol Metab 2009; 23: 463–477.

27. Williams DL. Minireview: finding the sweet spot: peripheral versus central glucagon-like peptide 1 action in feeding and glucose homeostasis. Endocrinology 2009; 150: 2997–3001.

28. Field BC, Chaudhri OB, Bloom SR. Bowels control brain: gut hormones and obesity. Nat Rev Endocrinol 2010; 6: 444–453.

29. Abbas T, Faivre E, Hölscher C. Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer’s disease. Behav Brain Res 2009; 205: 265–271.

30. Gault VA, Hölscher C. GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid. Eur J Pharmacol 2008; 587: 112–117.

31. Haluzík M, Svačina Š. Inkretinová léčba diabetu. Praha: Mladá Fronta 2010.

32. 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: 955–961.

33. Sokos GG, Nikolaidis LA, Mankad S et al. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 2006; 12: 694–699.

34. 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: 962–965.

35. 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: 824–829.

36. Buse JB, Bergenstal RM, Glass LC et al. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med 2011; 154: 103–112.

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