The American Journal of Medicine
Volume 122, Issue 6, Supplement , Pages S37-S50 , June 2009

Clinical Application of Incretin-Based Therapy: Therapeutic Potential, Patient Selection and Clinical Use

References 

  1. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104:787–794
  2. Gallwitz B. The fate of Beta-cells in type 2 diabetes and the possible role of pharmacological interventions. Rev Diabet Stud. 2006;3:208–216
  3. Unger RH. Reinventing type 2 diabetes: pathogenesis, treatment, and prevention. JAMA. 2008;299:1185–1187
  4. Karter AJ, Moffet HH, Liu J, et al. Glycemic response to newly initiated diabetes therapies. Am J Manag Care. 2007;13:598–606
  5. Cook MN, Girman CJ, Stein PP, Alexander CM. Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycemic goals in patients with Type 2 diabetes in UK primary care. Diabet Med. 2007;24:350–358
  6. Salber PR, Bestermann W, Schwartz S, Marchetti A. Loss of confidence in diabetes management. Manag Care. 2008;17:38–46
  7. Doggrell SA. Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect. Expert Opin Pharmacother. 2002;3:1011–1013
  8. Castaneda C. Diabetes control with physical activity and exercise. Nutr Clin Care. 2003;6:89–96
  9. Nathan DM, Buse JB, Davidson MB, et al. American Diabetes Association and the European Association for the Study of Diabetes Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy (A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes). Diabetes Care. 2009;32:193–203
  10. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853
  11. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002;287:360–372
  12. Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008;57:3169–3176
  13. Pitocco D, Valle D, Rossi A, Gentilella R. Unmet needs among patients with type 2 diabetes and secondary failure to oral anti-diabetic agents. J Endocrinol Invest. 2008;31:371–379
  14. Blonde L. State of diabetes care in the United States. Am J Manag Care. 2007;13(suppl 2):S36–S40
  15. American Diabetes Association. Executive summary: standards of medical care in diabetes—2009. Diabetes Care. 2009;32:S6–S12
  16. Turner RC, Cull CA, Frighi V, Holman RR UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281:2005–2012
  17. Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care. 2004;27:17–20
  18. Saaddine JB, Cadwell B, Gregg EW, et al. Improvements in diabetes processes of care and intermediate outcomes: United States, 1988-2002. Ann Intern Med. 2006;144:465–474
  19. Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is glycemic control improving in U.S. adults?. Diabetes Care. 2008;31:81–86
  20. Patel A, MacMahon S, Chalmers J, et al. ADVANCE Collaborative Group Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–2572
  21. Gerstein HC, Miller ME, Byington RP, et al. ACCORD (Action to Control Cardiovascular Risk in Diabetes) Study Group Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–2559
  22. Nichols GA, Gomez-Caminero A. Weight changes following the initiation of new anti-hyperglycemic therapies. Diabetes Obes Metab. 2007;9:96–102
  23. Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab. 2001;86:3717–3723
  24. Vilsbøll T, Krarup T, Deacon CF, et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001;50:609–613
  25. Ryskjaer J, Deacon CF, Carr RD, et al. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake. Eur J Endocrinol. 2006;155:485–493
  26. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993;91:301–307
  27. Meier JJ, Hücking K, Holst JJ, et al. Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes. 2001;50:2497–2504
  28. Turner RC, Cull CA, Stratton IM, et al. UK Prospective Diabetes Study (UKPDS) Group Overview of 6 years' therapy of type II diabetes: a progress disease (UKPDS 16). Diabetes. 1995;44:1249–1258
  29. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. β-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab. 2005;90:493–500
  30. Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986;29:46–52
  31. Nauck MA. Unraveling the science of incretin biology. Am J Med. 2009;122(suppl):S3–S10
  32. Gilbert MP, Pratley RE. Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus. Am J Med. 2009;122(suppl):S11–S24
  33. Hollman RR, Paul SK, Bethel A, et al. 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–1589
  34. Hollman RR, Paul SK, Bethel A, et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359:1565–1576
  35. American Diabetes Association. Position statement: standards of medical care in diabetes—2007. Diabetes Care. 2007;30:S4–S41
  36. ACE/AACE Diabetes Road Map Task Force. Road maps to achieve glycemic control in type 2 diabetes mellitus. Endocr Pract. 2007;13:260–268
  37. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2008;32(suppl 1):S1–S201
  38. Etzwiler DD, Mazze RS, Bergenstal RM. Diabetes translation: a blueprint for the future. Diabetes Care. 1994;17(suppl 1):1–4
  39. Mazze RS, Etzwiler DD, Strock E, et al. Staged diabetes management: toward an integrated model of diabetes care. Diabetes Care. 1994;17(suppl 1):S56–S66
  40. Rith-Najarian S, Branchaud C, Beaulieu O, et al. Reducing lower extremity amputation due to diabetes: application of staged diabetes management approach in a primary care setting. J Fam Pract. 1998;47:127–132
  41. Benjamin EM, Bradley R. Systematic implementation of customized guidelines: the staged diabetes management approach. J Clin Outcomes Manag. 2002;9:81–86
  42. Sidorov JE, Harris RE, Shull RD, et al. Disease management for diabetes mellitus: impact on hemoglobin A1c. Am J Manag Care. 2000;6:1217–1226
  43. Sidorov J, Shull R, Tomcavage J, et al. Does diabetes disease management save money and improve outcomes?. Diabetes Care. 2002;25:684–689
  44. Philis-Tsimikas A, Walker C, Rivard L, et al. Improvement in diabetes care of underinsured patients enrolled in Project Dulce. Diabetes Care. 2004;27:110–115
  45. Mazze RS, Strock E, Simonson GD, Bergenstal RM. Staged Diabetes Management: a Systematic Approach. 2nd ed (rev). Hoboken, NJ: John Wiley & Sons; 2006;
  46. Bergenstal RM. Treatment models from the International Diabetes Center: advancing from oral agents to insulin therapy in type 2 diabetes. Endocr Pract. 2006;12:98–104
  47. Mazze RS, Powers MA, Wetzler HP, Ofstead CL. Partners in advancing care and education solutions study: impact on processes and outcomes of diabetes care. Popul Health Manag. 2008;11:297–305
  48. Eriksson J, Franssila-Kallunki A, Ekstrand A, et al. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989;321:337–343
  49. Polonsky KS, Given BD, Hirsch LJ, et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med. 1988;318:1231–1239
  50. Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes. 2004;53(suppl 3):S16–S21
  51. Nyström T, Gutniak MK, Zhang Q, et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004;287:E1209–E1215
  52. Noyan-Ashraf H, Ban K, Sadi A, et al. The GLP-1R agonist liraglutide protects cardiomyocytes and improves survival and cardiac function after experimental murine myocardial infarction. In: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California. 2008;Oral Presentation 190
  53. Mudaliar S, Henry RR. Incretin therapies: effects beyond glycemic control. Am J Med. 2009;122(suppl):S25–S36
  54. Fisman EZ, Motro M, Tenenbaum A. Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects. Adv Cardiol. 2008;45:154–170
  55. Misbin RI, Green L, Stadel BV, et al. Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med. 1998;338:265–266
  56. Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147:386–399
  57. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–2471
  58. Meier C, Kraenzlin ME, Bodmer M, et al. Use of thiazolidinediones and fracture risk. Arch Intern Med. 2008;168:820–825
  59. 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
  60. Byetta (exenatide) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2007;
  61. 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
  62. 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
  63. 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
  64. 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
  65. 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
  66. 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
  67. Barnett AH, Burger J, Johns D, et al. Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther. 2007;29:2333–2348
  68. Bunck MC, Diamant MA, Corner EB, et al. One year treatment with exenatide improves beta cell function and glycaemic control in metformin treated type 2 diabetes patients. In: Presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes; September 17-21. Amsterdam, Holland. 2007;Abstract 07-175
  69. 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
  70. Agersø H, Jensen LB, Elbrønd B, et al. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002;45:195–202
  71. 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
  72. Zinman B, Gerich J, Buse J, et al. Efficacy and safety of the human GLP-1 analog liraglutide in combination with metformin and TZD in type 2 diabetes mellitus (LEAD-4 Met+TZD). Diabetes Care. 2009;Mar 16. [Epub ahead of print]
  73. Blonde L, Rosenstock J, Sesti G, et al. Liraglutide: superior glycaemic control vs exenatide when added to metformin and/or SU in type 2 diabetes. Can J Diabetes. 2008;32(suppl):29
  74. Stewart MW, Matthews J, De Boever EH, et al. Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide (Syncria®), a long-acting GLP-1 mimetic, in subjects with type 2 diabetes. In: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California. 2008;Abstract 519-P
  75. Nauck MA, Ratvier RE, Kapitza C, Berria R, Boldrin M, Balena R. Treatment with the human once-weekly GLP-1 analogue taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes mellitus inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care. 2009;Apr 14. [Epub ahead of print]
  76. 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
  77. Davis SN, Johns D, Maggs D, et al. Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents. Diabetes Care. 2007;30:2767–2772
  78. Rosenstock J, Fonseca V. Missing the point: substituting exenatide for nonoptimized insulin—going from bad to worse!. Diabetes Care. 2007;30:2972–2973
  79. Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007;29:139–153
  80. Marre M, Shaw J, Brandle M, et al. Liraglutide, a once-daily human GLP-1 analogue, plus a sulphonylurea improves glycaemic and weight control more than a sulphonylurea plus rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med. 2009;26:268–278
  81. Nauck M, Frid A, Hermansen K, et al. LEAD-2 Metformin Study Group Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin in type 2 diabetes mellitus (LEAD-2 Met). Diabetes Care. 2009;32:84–90
  82. 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: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, CA. 2008;Abstract 536-P
  83. Russell-Jones DS, Shaw J, Brandle M, et al. The once-daily human glucagon-like peptide-1 analog liraglutide reduces bodyweight in subjects with type 2 diabetes, irrespective of body mass index at baseline. In: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California. 2008;Abstract 2147-PO
  84. Blonde L, Klein EJ, Han J, et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006;8:436–447
  85. Okerson T, Yan P, Stonehouse A, et al. Exenatide improved systolic blood pressure compared to insulin or placebo in patients with type 2 diabetes. In: Program and Abstracts of the 44th Annual Meeting of the European Association for the Study of Diabetes (EASD); September 7-11. Rome, Italy. 2008;Abstract 877
  86. Bergenstal R, Kim T, Trautmann M, et al. Exenatide once weekly elicited improvements in blood pressure and lipid profile over 52 weeks in patients with type 2 diabetes. In: Program and Abstracts of the American Heart Association Scientific Sessions; November 9. New Orleans, Louisiana. 2008;Abstract 1239
  87. Colagiuri S, Frid A, Zdravkovic M, et al. The once-daily human GLP-1 analog liraglutide reduces systolic blood pressure in patients with type 2 diabetes. In: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California. 2008;Abstract 554-P
  88. 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
  89. Matthews D, Marre M, Le Thi TD, et al. Liraglutide, a once-daily human GLP-1 analog, significantly improves β-cell function in subjects with type 2 diabetes. In: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California. 2008;Abstract 505-P
  90. Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes. 1999;48:2270–2276
  91. Farilla L, Hui H, Bertolotto C, et al. Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology. 2002;143:4397–4408
  92. Buteau J, Foisy S, Rhodes CJ, et al. Protein kinase Czeta activation mediates glucagon-like peptide-1-induced pancreatic beta-cell proliferation. Diabetes. 2001;50:2237–2243
  93. Mari A, Degn K, Brock B, et al. Effects of the long-acting human glucagons-like peptide-1 analog liraglutide on beta-cell function in normal living conditions. Diabetes Care. 2007;30:2032–2033
  94. Fehse F, Trautmann M, Holst JJ, et al. Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2005;90:5991–5997
  95. Degn KB, Juhl CB, Sturis J, et al. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and α- and β-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004;53:1187–1194
  96. Vilsbøll T, Brock B, Perrild H, et al. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic β-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med. 2008;25:152–156
  97. Chang AM, Jakobsen G, Sturis J, et al. The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes. 2003;52:1786–1791
  98. Helleberg H, Malm-Erjefält M, Bjørnsdottir I, et al. Metabolism and excretion of [Pal-3H]-liraglutide in human healthy subjects. In: Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California. 2007;Abstract 2107-PO
  99. Jacobsen LV, Hindsberger C, Robson R, Zdravkovic M. Pharmacokinetics of the long-acting human GLP-1 analogue liraglutide in subjects with renal impairment. In: Program and Abstracts of the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD); September 17-21. Amsterdam, the Netherlands. 2007;Abstract 0852
  100. 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: Program and Abstracts of the American Diabetes Association (ADA) 67th Sessions; June 22-26. Chicago, Illinois. 2007;Abstract 545-P
  101. Jacobsen LV, Hindsberger C, Robson R, Zdravkovic M. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br J Clin Pharmacol. In press.
  102. Hill M. FDA notes 2 Byetta deathsWebMD Health News. http://www.medicinenet.com/script/main/art.asp?articlekey=91985Accessed January 8, 2009
  103. Noel R, Braun D, Patterson R, Bloomgren G. Increased risk of acute pancreatitis observed in patients with type 2 diabetes. In: Program and Abstracts of the 24th International Conference on Pharmacoepidemiology and Therapeutic Risk Management; August 17-20. Copenhagen, Denmark. 2008;Abstract 409
  104. Blomgren KB, Sundström A, Steineck G, Wiholm BE. Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. Diabetes Care. 2002;25:298–302
  105. De Santis A, Attili AF, Ginanni Corradini S, et al. Gallstones and diabetes: a case-control study in a free-living population sample. Hepatology. 1997;25:787–790
  106. Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am. 1990;19:783–791
  107. 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 7, 2008
  108. Exenatide (marketed as BYETTA): acute pancreatitis [postmarketing review]. FDA Drug Safety Newsletter Winter. 2008;1:12–14http://www.fda.gov/CDER/dsn/2008_winter/postmarketing.htmAccessed January 8, 2009
  109. US Food and Drug Administration. Exenatide (marketed as Byetta)Information for Healthcare Professionals [FDA Website]. www.fda.gov/cder/drug/InfoSheets/HCP/exenatide2008HCP.htmAccessed January 8, 2008
  110. Charbonnel B, Karasik A, Liu J, et al. Sitagliptin Study 020 Group 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
  111. Aschner P, Kipnes MS, Lunceford JK, et al. Sitagliptin Study 021 Group 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
  112. Goldstein BJ, Feinglos MN, Lunceford JK, et al. Sitagliptin 036 Study Group 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
  113. Hermansen K, Kipnes M, Luo E, et al. Sitagliptin Study 035 Group 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
  114. Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes. Diabetes Res Clin Pract. 2007;76:132–138
  115. Rosenstock J, Kim SW, Baron MA, et al. 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
  116. Bosi E, Camisasca RP, Collober C, et al. 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
  117. Rosenstock J, Foley JE, Rendell M, et al. Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance. Diabetes Care. 2008;31:30–35
  118. 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
  119. Brazg R, Xu L, Dalla Man C, et al. Effect of adding sitagliptin, a dipeptidyl peptidase-4 inhibitor, to metformin on 24-h glycaemic control and beta-cell function in patients with type 2 diabetes. Diabetes Obes Metab. 2007;9:186–193
  120. Balas B, Baig MR, Watson C, et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007;92:1249–1255
  121. Ahrén B, Pacini G, Foley JE, Schweizer A. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care. 2005;28:1936–1940
  122. Mari A, Scherbaum WA, Nilsson PM, et al. Characterization of the influence of vildagliptin on model-assessed β-cell function in patients with type 2 diabetes and mild hyperglycemia. J Clin Endocrinol Metab. 2008;93:103–109
  123. Ristic S, Byiers S, Foley J, Holmes D. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab. 2005;7:692–698
  124. Januvia (sitagliptin) [package insert]. Whitehouse, Station, NJ: Merck & Co., Inc; 2007;
  125. He YL. The influence of hepatic impairment on the pharmacokinetics of vildagliptin. In: Program and Abstracts of the American Diabetes Association (ADA) 66th Sessions; June 9-13. Washington, DC. 2006;Abstract 2024-PO
  126. European Medicines Agency Website Galvus® annex I: summary of product characteristics. www.emea.europa.eu/humandocs/PDF/EPAR/galvus/H-771-PI-en.pdfAccessed January 8, 2009
  127. Mehta N. Novartis ties up with USV to market Galvus in India. The Economic Times [serial online]. November 27, 2008 http://economictimes.indiatimes.com/News_by_Industry/Novartis_ties_up_with_USV/articleshow/3761728.cmsAccessed January 8, 2009
  128. Nathan DM, Cleary PA, Backlund JY, et al. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643–2653
  129. Yamagishi S, Matsui T, Nakamura K. Blockade of the advanced glycation end products (AGEs) and their receptor (RAGE) system is a possible mechanism for sustained beneficial effects of multifactorial intervention on mortality in type 2 diabetes. Med Hypotheses. 2008;71:749–751

 Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

PII: S0002-9343(09)00279-4

doi: 10.1016/j.amjmed.2009.03.015

The American Journal of Medicine
Volume 122, Issue 6, Supplement , Pages S37-S50 , June 2009

Article Tools

* Image Usage & Resolution