European Journal of Internal Medicine
Volume 20 , Pages S309-S318 , July 2009

Efficacy and Safety of Incretin-Based Therapies in Patients with Type 2 Diabetes Mellitus

  • Matthew P. Gilbert, DO, MPH
  • ,
  • Richard E. Pratley, MD

      Affiliations

    • Corresponding Author InformationCorresponding author. Requests for reprints should be addressed to Richard E. Pratley, MD, Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Given C33189, Beaumont Avenue, Burlington, Vermont 05405.

References 

  1. Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359:1565–1576
  2. Kendall DM, Cuddihy RM, Bergenstal RM. Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Am J Med. 2009;122(suppl):S37–S50
  3. Byetta (exenatide injection) [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc; 2007;
  4. Nielsen LL, Young AA, Parkes DG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept. 2004;117:77–88
  5. Kim D, MacConell L, Zhuang D, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007;30:1487–1493
  6. Ritzel U, Leonhardt U, Ottleben M, et al. A synthetic glucagon-like peptide-1 analog with improved plasma stability. J Endocrinol. 1998;159:93–102
  7. Vilsboll T. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs. 2007;16:231–237
  8. Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002;45:195–202
  9. Helleberg H, Malm-Erjefält M, Bjørnsdottir I, et al. Metabolism and excretion of [Pal-3H]-liraglutide in human healthy subjects. In: Presented at the 68th Scientific Sessions of the American Diabetes Association; June 6-10. San Francisco, CA. 2008;Abstract 2107-PO
  10. Jacobsen V, Hindsberger C, Robson R, Zdravkovic M. Pharmacokinetics of the long-acting human GLP-1 analogue liraglutide in subjects with renal impairment. In: Presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes; September 17-21. Amsterdam, Netherlands. 2007;Abstract 0852
  11. Flint A, Nazzal K, Jagielski P, Segel S, Zdravkovic M. Influence of hepatic impairment on pharmacokinetics of the long-acting human glp-1 analogue liraglutide. In: Presented at the 67th Scientific Sessions of the American Diabetes Association; June 22-26. Chicago, IL. 2007;Abstract 054-P
  12. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006;29:2638–2643
  13. Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol. 2006;38:831–844
  14. Januvia (sitagliptin) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2007;
  15. He YL, Sabo R, Wang Y, Ligueros-Saylan M, Dole WP. The influence of hepatic impairment on the pharmacokinetics of vildagliptin. In: Presented at the 66th Scientific Sessions of the American Diabetes Association; June 9-13. Washington, DC. 2006;Abstract 2024-PO
  16. European Medicines Agency Website Galvus® annex I: summary of product characteristics. http://www.emea.europa.eu/humandocs/PDF/EPAR/galvus/H-771-PI-en.pdfAccessed December 18, 2008
  17. New data for Galvus® provide further evidence of robust efficacy and tolerability in treating patients with type 2 diabetes [media release]. [Novartis Website.] Basel, Switzerland: Novartis; 2007;September 17 http://www.novartis.com/newsroom/media-releases/en/2007/1153741.shtmlAccessed December 18, 2008
  18. Moretto TJ, Milton DR, Ridge TD, et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2008;30:1448–1460
  19. Garber A, Henry R, Ratner R, et al. LEAD-3 (Mono) Study Group Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373:473–481
  20. Garber A, Henry R, Ratner R, et al. Significantly better glycemic control and weight reduction with liraglutide, a once-daily human GLP-1 analog, compared with glimepiride: all as monotherapy in type 2 diabetes. In: Presented at the 44th Annual Meeting of the European Association for the Study of Diabetes; September 7-11. Rome, Italy. 2008;Abstract 896
  21. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29:2632–2637
  22. Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia. 2006;49:2564–2571
  23. Schweizer A, Couturier A, Foley JE, Dejager S. Comparison between vildagliptin and metformin to sustain reductions in HbA1c over 1 year in drug-naive patients with Type 2 diabetes. Diabet Med. 2007;24:955–961
  24. Vilsbøll T, Zdravkovic M, Le Thi T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care. 2007;30:1608–1610
  25. DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. 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
  26. Nauck M, Frid A, Hermansen K, et al. LEAD-2 Study Group Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32:84–90
  27. Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007;30:1979–1987
  28. Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care. 2007;30:890–895
  29. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. 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
  30. Marre M, Shaw J, Brändle M, et al. LEAD-1 SU study group Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med. 2009;26:268–278
  31. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007;9:733–745
  32. Garber AJ, Foley JE, Banerji MA, et al. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab. 2008;10:1047–1056
  33. Zinman B, Hoogwerf BJ, Duran GS, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007;146:477–485
  34. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. 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
  35. Rosenstock J, Baron MA, Camisasca RP, Cressier F, Couturier A, Dejager S. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes. Diabetes Obes Metab. 2007;9:175–185
  36. Garber AJ, Schweizer A, Baron MA, Rochotte E, Dejager S. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study. Diabetes Obes Metab. 2007;9:166–174
  37. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083–1091
  38. 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
  39. Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005;143:559–569
  40. Russell-Jones D, Vaag A, Schmitz O, et al. Significantly better glycemic control and weight reduction with liraglutide, a once-daily human GLP-1 analog, compared with insulin glargine: all as add-on to metformin and a sulfonylurea in type 2 diabetes. In: Presented at the American Diabetes Association's 68th Sessions; June 6-10. San Francisco, CA. 2008;Abstract 536-P
  41. Zinman B, Gerich J, Buse JB, et al. Efficacy and safety of the human GLP-1 analog liraglutide in combination with metformin and TZD in patients with type 2 diabetes mellitus (LEAD-4 Met+TZD). Diabetes Care. 2009;Mar 16. [Epub ahead of print]
  42. Davies M, Lavalle-González F, Storms F, Gomis R AT.LANTUS Study Group. Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial. Diabetes Obes Metab. 2008;10:387–399
  43. Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia. 2007;50:1148–1155
  44. Hermansen K, Nauck M, Frid A, et al. Liraglutide, a once-daily human GLP-1 analogue, in type 2 diabetes provides similar glycaemic control with reduced bodyweight compared with glimepiride when added to metformin. In: Presented at the 44th Annual Meeting of the European Association for the Study of Diabetes; September 7-11. Rome, Italy. 2008;Abstract 895
  45. Drucker DJ, Buse JB, Taylor K, et al. 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
  46. Amylin Pharmaceuticals and Eli Lilly and Company. Important prescribing information for healthcare professionals, October 2007 [letter]. [FDA Website.] http://www.fda.gov/medwatch/safety/2007/byetta_dhcp-letter.pdfAccessed November 19, 2008
  47. Noel R, Braun D, Patterson R, Bloomgren G. Increased risk of acute pancreatitis observed in patients with type 2 diabetes. In: Presented at the 24th International Conference on Pharmacoepidemiology and Therapeutic Risk Management; August 17-20. Copenhagen, Denmark. 2008;Abstract 409
  48. 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

 This article is a copublication with The American Journal of Medicine, 122, S11-S24. For citation purposes please use European Journal of Internal Medicine, 20, S309-S318.

PII: S0953-6205(09)00096-X

doi: 10.1016/j.ejim.2009.05.011

European Journal of Internal Medicine
Volume 20 , Pages S309-S318 , July 2009