||The treatment options for type 2 diabetes mellitus (T2DM) have increased significantly over the past 10 to 15 years. Incretin hormones, which are found in the gastrointestinal system and other tissues, are integral to glucose homeostasis, increasing insulin secretion, reducing glucagon secretion, slowing gastric emptying, and enhancing early satiety. Enhancement of the incretin system with GLP-1(glucagon like peptide 1) receptor agonists and DPP-4(dipeptidyl peptidase 4) is effective in reestablishing glucose homeostasis.
Exenatide, a twice-daily injectable GLP-1 receptor agonist, was approved in 2005 by the FDA for the treatment of type 2 diabetes mellitus (T2DM).The author suggests to evaluate the efficacy and safety of exenatide in patients with T2DM not adequately controlled with metformin (1500-2500 mg/d); primary endpoint: HbA1C(glycosylated hemoglobin) change after 48 weeks, secondary endpoint: fasting plasma glucose, postprandial glucose, body weight change, hypoglycemia, adverse events. The study was conducted on the Emergency Clinical County Hospital of Arad, Diabetes Mellitus Department, during June 2011-July 2012 and comprises 24 patients admitted in the hospital for diabetological disorders, treat with metformin 1500-2500 mg daily.
||1. Aaboe K, Krarup T, Madsbad S, Holst JJ: GLP-1 Phyziological Effects And Potential Therapeutic Application, Diabetes Obes Metab 2008: 10: 994-1003
2. Ahren B: Gut Peptides And Type 2 Diabetes Mellitus Treatment, Curr. Diab. Rep. 2003; 3: 365-72
3. Amori RE, Lau J, Pittas AG: Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 2007; 298: 194-206
5. Deacon CF, Wamberg S, Bie P, Hughes TE, Holst JJ: Preservation Of Active Incretin Hormones By Inhibition Of Dipeptidyl Peptidase IV Suppresses Meal-Induced Incretin Secretion In Dogs, J. Endocrinol. 172, 2002: 355-362
7. Deacon CF, Nauck MA, Toft-Nielsen M, et al. Both sc and iv administered glucagon-like peptide-1 are rapidly degraded from the NH2-terminus in type II diabetic patients and healthy subjects. Diabetes 1995; 44: 1126-31
8. DeFronzo RA: From The Triumvirate To The Ominous Octet: A New Paradigm For The Treatment Of Type 2 Diabetes Mellitus, Diabetes 2009; 58: 773-95
9. Drucker DJ, Nauck MA: The Incretin System: Glucagon Like Peptide – 1 Receptor Agonists And Dipeptidyl Peptidase – 4 Inhibitors In Type 2 Diabetes, Lancet 2006; 368: 1696-705
10. Drucker DJ. The evidence for achieving glycemic control with incretin mimetics. Diabetes Educ.32 (Suppl. 2), 2006: 72S-81S
11. Filip K. Knop; Tina Vilsbøll; Patricia V. Højberg; Steen Larsen, et al: Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State?
Diabetes. 2007; 56(8):1951-1959
12. Hancu N, Roman G, Veresiu IA: Farmacoterapia diabetului zaharat, ed. Echinox, Cluj-Napoca, 2008; 169-184
14. Holst JJ, Deacon CF: Inhibition Of The Activity Of The Dipeptidyl Peptidase IV As Treatment For Type 2 Diabetes, Diabetes (47), 1998: 1663-16670
15. Jellinger PS, Davidson JA, Blonde L, et al. Road maps to achieve glycemic control in type 2 diabetes mellitus: ACE/AACE Diabetes Road Map Task Force. Endocr Pract 2007; 13(3): 260-268
19. Kent DM, Hayward RA. Limitations of applying summary results of clinical trials to individual patients: the need for risk stratification. JAMA. 2007; 298:1209-1212.
20. Muscelli E, Mari A, Natali A, Astiarraga BD, et al: Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab (291), 2006:E1144-E1150.
21. Nathan DM, Buse JB et al. Management of hyperglycemia in Type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American diabetes association and the European Association for the Study of Diabetes. Diabetes Care (29), 2006:1963-1972
23. Nauck MA, Meier JJ, Creutzfeldt W. Incretins and their analogues as new antidiabetic drugs. Drug News Perspect. (16), 2003:413-422
24. Nichols GA, Koro CE,.Gullion CM, Ephross S, Brown JB: The Incidence Of Congestive Heart Failure Associated With Antidiabetic Therapies, Diabetes Metab. Res. Rev. 2005; 21 (1): 51-7
26. Rodbard HW, Jellinger PS, Davidson JA et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009; 15:540-559
27. Seck T, Nauck M, et al.: Safety and Efficacy of Treatment with Sitagliptin or Glipizide in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A 2-year Study Int J Clin Pract. 2010; 65(5):562-576
29. Tzoulaki I, Molokia M, et al: Risk Of Cardiovascular Disease All-Cause Mortality Among Patients With Type 2 Diabetes Prescribed Oral Antidiabetic Drugs: Retrospective Cohort Study Using UK General Practice Research Database, BMJ, 2009; 339