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Thursday, March 26, 2009

Nonglycemic Effects of Incretins

In addition to their beneficial effects on blood glucose, particularly postprandial glucose, as well as body weight and pancreatic beta cell function, the glucagon-like peptide-1 (GLP-1) receptor agonists (Exenatide, Liraglutide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (Sitagliptin, Vildagliptin) have other beneficial effects. These effects on blood pressure and blood lipids, although not making incretins suitable as primary therapy, may be important benefits to consider in selecting diabetes therapy, because patients with type 2 diabetes mellitus (T2DM) are at increased risk for cardiovascular disease.

Blood Pressure


GLP-1 receptor agonists and DPP-4 inhibitors produce modest reductions in systolic blood pressure and, in some cases, diastolic blood pressure. The importance of hypertension as a cardiovascular risk factor is well established. As concluded by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, each increment of 20/10 mm Hg above 115/75 mm Hg doubles the risk of cardiovascular disease.

Lipid Profile

the GLP-1 receptor agonists and DPP-4 inhibitors produce significant reductions in the triglyceride level. Exenatide and vildagliptin also produce significant improvements in total, LDL-, and HDL-cholesterol. The benefits on reducing cardiovascular risk by lowering total and LDL-cholesterol and raising HDL-cholesterol are well established. As such, they are important targets for treatment as recommended by the National Cholesterol Education Program Expert Panel - Adult Treatment Panel III

Conclusion

The GLP-1 receptor agonists and DPP-4 inhibitors lower blood pressure and improve the lipid profile, which, although not appropriate as primary therapy, makes them especially valuable treatment options for patients with T2DM. These improvements may help to reduce the risk of cardiovascular events. Various approaches can be taken to initiate and modify GLP-1 receptor agonist and DPP-4 inhibitor therapy to improve efficacy and tolerability based on patient characteristics and concomitant therapies.

References

  1. Boschmann M, Engeli S, Dobberstein K, et al. Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients. J Clin Endocrinol Metab. 2008. In press.
  2. Viswanathan P, Chaudhuri A, Bhatia R, et al. Exenatide therapy in obese patients with type 2 diabetes mellitus treated with insulin. Endocr Pract. 2007;13:444-450.
  3. Ratner RE, Maggs D, Nielsen LL, et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2006;8:419-428.
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  8. Blonde L, Rosenstock J, Sesti G, et al. Liraglutide: superior glycemia control vs exenatide when added to metformin and/or SU in type 2 diabetes. Paper presented at: Canadian Diabetes Association/Canadian Society of Endocrinology and Metabolism Annual Meeting; October 15-18, 2008; Montreal, Quebec, Canada.
  9. Scott R, Wu M, Sanchez M, et al. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract. 2007;61:171-180.
  10. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P; for the Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006;28:1556-1568.
  11. Bolli G, Dotta F, Rochotte E, et al. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study. Diabetes Obes Metab. 2008;10:82-90.
  12. Rosenstock J, Baron MA, Dejager S, Mills D, Schweizer A. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes. Diabetes Care. 2007;30:217-223.
  13. Grundy SM, Becker D, Clark LT, et al. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Final report. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf. Accessed January 20, 2009.
  14. Daniel A. Nadeau, MD. Incretin Benefits Beyond Glycemic Control. From Primary Care Education Consortium, Medscape Internal Medicine. Posted 03/19/2009. Available at: http://www.medscape.com/viewarticle/588945?src=mp&spon=18&uac=82830HJ

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