Non-Insulin Injectables

  • Ronald A. Codario
Part of the Current Clinical Practice book series (CCP)


The description of the incretin effect was first described in 1964 by Elwick when he observed a greater insulin secretory response if glucose was administered orally compared to intravenously despite similar elevations in plasma glucose. This incretin effect is attributed to the release of peptide hormones from the K and L cells in the intestines in the response to eating, so that approximately 60% of the insulin subsequently secreted is related directly to the effect of incretins [1]. Glucagon like peptide-1 (GLP-1) is secreted by the L cells, suppresses postprandial glucagon secretion, reduces appetite and stimulates insulin secretion in a dose dependent manner.

Key Words

GLP-1 analogs (incretin mimetics) Amylin analogs Incretin K and L cells Glucagon like peptide 1 (GLP-1) Postprandial glucagon secretion 


  1. 1.
    Nauck M. Unraveling the science of indretin biology. Am J Med. 2009;122(6A):S3–S24.PubMedCrossRefGoogle Scholar
  2. 2.
    Drucker DJ, Nauck MA. The incretin system. Lancet. 2006;368:1696–1705.PubMedCrossRefGoogle Scholar
  3. 3.
    Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132:2131–2157.PubMedCrossRefGoogle Scholar
  4. 4.
    Eissele R, Goke R, Willemer S. Glucagon like peptide cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest. 1992;22:283–291.PubMedCrossRefGoogle Scholar
  5. 5.
    Nauck MA, Baller B, Meier JJ. Gastric inhibitory polypeptide and glucagon like peptide-1 in the pathogenesis of type-2 diabetes. Diabetes. 2004;53(suppl 3):S190–S196.PubMedCrossRefGoogle Scholar
  6. 6.
    Nauck MA, Stockman F, Ebert R, Creutzfeldt W. Reduced incretin effect in type-2 diabetes. Diabetologia. 1986;29:46–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Meier JJ, Goetze O, Anstipp J. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans. Am J Physiol Endocrinol Metab. 2004:286:E621–E625.PubMedCrossRefGoogle Scholar
  8. 8.
    Li Y, Cao X, Li LX. Beta cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Diabetes. 2005;54:482–491.PubMedCrossRefGoogle Scholar
  9. 9.
    Meier JJ, Gallwitz B, Kask B. Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptidein patients with type-2 diabetes and healthy control subjects. Diabetes. 2004;53(suppl 3):S220–S224.PubMedCrossRefGoogle Scholar
  10. 10.
    Nauck MA. Glucagon-like peptide-1 in type-2 diabetes: the beta cell and beyond. Diabetes Obes Metab. 2008;10(suppl 3):2–13.CrossRefGoogle Scholar
  11. 11.
    Cervera A, Wajcberg E, Sriwijitkamol A. Mechanism of action of exenatide treatment on A1C, weight and cardiovascular risk factors. Diabetes Obes Metab. 2006;8:436–447.CrossRefGoogle Scholar
  12. 12.
    Nielsen L, Baron A, Pharmacology of exenatide for the treatment of type-2 diabetes. Curr Opin Investig Drugs. 2003;4:401–405.PubMedGoogle Scholar
  13. 13.
    Kolterman O, Kim DD, Shen L. Pharmacokinetics, pharmacodynamics and safety of exenatide in patients with type-2 diabetes mellitus. Am Health Syst Pharm. 2005;62:173–181.Google Scholar
  14. 14.
    Kendall DM, Riddle MC, Rosenstock J. effects of exenatide on glycemic control over 30 weeks in patients with type-2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083–1091.PubMedCrossRefGoogle Scholar
  15. 15.
    Heine RJ, Van Gaal LF, Johns D. Exenatide versus insulin glargine in patients with suboptimally controlled type-2 diabetes. Ann Intern Med. 2005;143:559–569.PubMedCrossRefGoogle Scholar
  16. 16.
    Buse JB, Klonoff DC, Nielson LL. Metabolic effect of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type-2 diabetes. Clin Ther. 2007;29:139–153.PubMedCrossRefGoogle Scholar
  17. 17.
    Nauck MA, Duran S, Kim D. A comparison of twice daily exenatide and biphasic insulin aspart in patients with type-2 diabetes who were suboptimally controlled with sulfonylurea and metformin. Diabetologia. 2007;50:259–267.PubMedCrossRefGoogle Scholar
  18. 18.
    Barnett AH, Trautmann M, Burger J, Johns D, Kim D, Brodows R, Festa A. A comparison of exenatide and insulin glargine in patients using a single oral diabetic agent. Data disclosure at the 42 annual meeting of the European Association of Diabetes. September 16, 2006.Google Scholar
  19. 19.
    Heine R, Van Gaal L, Johns D, Mihm M. Exenatide versus insulin glargine in patients with suboptimally controlled type-2 diabetes. Ann Intern Med. 2005;143(8):559–569.PubMedCrossRefGoogle Scholar
  20. 20.
    Cure P. Exenatide and adverse events. New Engl J Med. 2008;358:1969–1972.PubMedCrossRefGoogle Scholar
  21. 21.
    Zinman B, Hoogwerf BJ, Duran J, Garcia S. the effect of adding exenatide to a thiazolidinedione in suboptimally controlled type-2 diabetes. Ann Intern Med. 2007;146:477–485.PubMedCrossRefGoogle Scholar
  22. 22.
    Briceno RM, Lagari-Libhaber VS. Meneghini LF. Clinical observations study of the safety, effectiveness, and tolerability of exenatide in a real world setting. Diabetes. 2007;56(suppl 1):Abstract 2147-PO.Google Scholar
  23. 23.
    Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL. One year treatment with exenatide improves beta cell function compared with insulin glargine in metformin treated type-2 diabetic patients. Diabetes Care. 2009;32(5):762–768.PubMedCrossRefGoogle Scholar
  24. 24.
    Drucker DJ, Buse KB, Taylor K, Kendall DM. Exenatide once weekly versus twice daily for the treatment of type-2 diabetes. Lancet. 2008;372(9645):1240–1250.PubMedCrossRefGoogle Scholar
  25. 25.
    Vilsboll T, Zdravkovic M, Le-Thi T. Liraglutide, a long acting human glucagon like peptide-1 analog. Diabetes Care. 2007;30:1608–1610.PubMedCrossRefGoogle Scholar
  26. 26.
    Victoza (liraglutide) package insert. Princeton NJ: Novo Nordisk; 2010.Google Scholar
  27. 27.
    Nauck M, Frid A, Hermansen K. for the LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride and placebo all in combination with metformin in type-2 diabetes: the LEAD-2 study. Diabetes Care. 2009;32(1)84–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Buse JB, Rosenstock J, Sesti G. Liraglutide once a day versus exenatide twice a day for type-2 diabetes: a 26 week randomized, parallel group, multinational open label trial (LEAD-6). Lancet. 2009;374:39–47.PubMedCrossRefGoogle Scholar
  29. 29.
    Garber A, Henry R, Ratner R. Liraglutide versus glimepiride monotherapy for type-2 diabetes (LEAD-3). Lancet. 2009;373:473–481.PubMedCrossRefGoogle Scholar
  30. 30.
    Merani S, Truong W, Emamaullee JA, Toso C, Knudsen LB. Liraglutide improves glucose homeostasis in marginal mass islet transplantation in mice. Endocrinology. 2008;149(9):4322–4328.PubMedCrossRefGoogle Scholar
  31. 31.
    Mari A, Degn K, Brock B. Effects of the long acting human glucagon like peptide-1 analog liraglutide on beta cell function in normal living conditions. Diabetes Care. 2007;30:2032–2033.PubMedCrossRefGoogle Scholar
  32. 32.
    Kruger DF, Gatacomb PM, Owen Sk. Clinical implication of amylin and amylin deficiency. Diabetes Educ. 1999;25:389–398.PubMedCrossRefGoogle Scholar
  33. 33.
    Gedulin BR, Rink TJ, Young AA. Dose response for the glucagonostatic effect of amylin in rats. Metabolism. 1997;46:67–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Beeley NRA, Prickett KS. The amylin, CGRP and calcitonin family of peptides. Expert Opin Ther Pat. 1996:6:555–567.CrossRefGoogle Scholar
  35. 35.
    Young A. Amylin’s physiology and its role in diabetes. Curr Opin Endocrinol Diabetes. 1997;4:282–290.CrossRefGoogle Scholar
  36. 36.
    Samsom M, Szarka LA, Camilleri M, Vella A, Zinsmeister AR, Rizza RA. Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition. Am J Physiol. 2000;278:G946–G951.Google Scholar
  37. 37.
    Young AA, Vine W, Gedulin BR. Preclinical pharmacology of pramlintide in the rat: comparisons with human an rat amylin. Dur Develop Res. 1996;37:231–248.CrossRefGoogle Scholar
  38. 38.
    Hollander PA, Levy P, Fineman MS, Maggs DG, Shen LZ, Strobel SA. Pramlintide as an adjunct to insulin therapy improves longterm glycemic and weight control in patients with type-2 diabetes. Diabetes Care. 2003;26:784–790.PubMedCrossRefGoogle Scholar
  39. 39.
    Wysham C, Lush C, Zhang B, Maier H, Wilhelm K. Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type-2 diabetes. Curr Med Res Opin. 2008;24(1):79–85.PubMedCrossRefGoogle Scholar
  40. 40.
    Ryan GJ, Jobe LJ, Martin R. Pramlintide in the treatment of type-1 and type-2 diabetes mellitus. Clin Ther. 2005;27:1500–1512.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ronald A. Codario
    • 1
  1. 1.University of Pennsylvania Health System Thomas Jefferson University HospitalPhiladelphiaUSA

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