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

American Journal of Medicine

Volumn 122, Issue 6 SUPPL., 2009, Pages

  Kendall, David M ^a   Cuddihy, Robert M ^a   Bergenstal, Richard M ^a  

^a INTERNATIONAL DIABETES CENTER   (United States)

Author keywords

DPP 4 inhibitor; exenatide; GLP 1 receptor agonist; liraglutide; sitagliptin; vildagliptin

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALBIGLUTIDE; ALOGLIPTIN; AVE 0010; DIPEPTIDYL PEPTIDASE IV; EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GLIMEPIRIDE; GLIPIZIDE; GLUCAGON LIKE PEPTIDE 1; HEMOGLOBIN A1C; INCRETIN; INSULIN; LIRAGLUTIDE; MEGLITINIDE; METFORMIN; PIOGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; TASPOGLUTIDE; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ACUTE PANCREATITIS; ANAPHYLAXIS; ANGIONEUROTIC EDEMA; ARTICLE; BONE LESION; CARDIOVASCULAR RISK; CELL FUNCTION; CLINICAL EFFECTIVENESS; CLINICAL FEATURE; CLINICAL PRACTICE; CLINICAL TRIAL; DIARRHEA; DIET THERAPY; DISEASE COURSE; DRUG COST; DRUG DOSE TITRATION; DRUG MECHANISM; DRUG METABOLISM; EDEMA; FOOD INTAKE; HEPATIC ENZYME ELEVATION; HUMAN; HYPERTENSION; HYPOGLYCEMIA; INSULIN RELEASE; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PANCREAS ISLET BETA CELL; PATHOPHYSIOLOGY; PATIENT SELECTION; PHYSICAL ACTIVITY; PRIORITY JOURNAL; SIDE EFFECT; STEVENS JOHNSON SYNDROME; STOMACH ABSORPTION; WEIGHT GAIN; WEIGHT REDUCTION; BLOOD; DRUG EFFECT; GLUCOSE BLOOD LEVEL; METABOLISM; REVIEW; TREATMENT OUTCOME;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; HUMANS; INCRETINS; PATIENT SELECTION; TREATMENT OUTCOME;

EID: 67049132386     PISSN: 00029343     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.amjmed.2009.03.015     Document Type: Article

References (129)

1. Weyer C., Bogardus C., Mott D.M., and Pratley R.E. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104 (1999) 787-794
2. Gallwitz B. The fate of Beta-cells in type 2 diabetes and the possible role of pharmacological interventions. Rev Diabet Stud 3 (2006) 208-216
3. Unger R.H. Reinventing type 2 diabetes: pathogenesis, treatment, and prevention. JAMA 299 (2008) 1185-1187
4. Karter A.J., Moffet H.H., Liu J., et al. Glycemic response to newly initiated diabetes therapies. Am J Manag Care 13 (2007) 598-606
5. Cook M.N., Girman C.J., Stein P.P., and Alexander C.M. 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 24 (2007) 350-358
6. Salber P.R., Bestermann W., Schwartz S., and Marchetti A. Loss of confidence in diabetes management. Manag Care 17 (2008) 38-46
7. Doggrell S.A. Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect. Expert Opin Pharmacother 3 (2002) 1011-1013
8. Castaneda C. Diabetes control with physical activity and exercise. Nutr Clin Care 6 (2003) 89-96
9. Nathan D.M., Buse J.B., Davidson M.B., 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 32 (2009) 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 352 (1998) 837-853
11. Inzucchi S.E. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 287 (2002) 360-372
12. Cryer P.E. The barrier of hypoglycemia in diabetes. Diabetes 57 (2008) 3169-3176
13. Pitocco D., Valle D., Rossi A., and Gentilella R. Unmet needs among patients with type 2 diabetes and secondary failure to oral anti-diabetic agents. J Endocrinol Invest 31 (2008) 371-379
14. Blonde L. State of diabetes care in the United States. Am J Manag Care 13 suppl 2 (2007) S36-S40
15. American Diabetes Association. Executive summary: standards of medical care in diabetes-2009. Diabetes Care 32 (2009) S6-S12
16. Turner R.C., Cull C.A., Frighi V., Holman R.R., and 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 281 (1999) 2005-2012
17. Koro C.E., Bowlin S.J., Bourgeois N., and Fedder D.O. Glycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care 27 (2004) 17-20
18. Saaddine J.B., Cadwell B., Gregg E.W., et al. Improvements in diabetes processes of care and intermediate outcomes: United States, 1988-2002. Ann Intern Med 144 (2006) 465-474
19. Hoerger T.J., Segel J.E., Gregg E.W., and Saaddine J.B. Is glycemic control improving in U.S. adults?. Diabetes Care 31 (2008) 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 358 (2008) 2560-2572
21. Gerstein H.C., Miller M.E., Byington R.P., 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 358 (2008) 2545-2559
22. Nichols G.A., and Gomez-Caminero A. Weight changes following the initiation of new anti-hyperglycemic therapies. Diabetes Obes Metab 9 (2007) 96-102
23. Toft-Nielsen M.B., Damholt M.B., Madsbad S., et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 86 (2001) 3717-3723
24. Vilsbøll T., Krarup T., Deacon C.F., et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50 (2001) 609-613
25. Ryskjaer J., Deacon C.F., Carr R.D., 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 155 (2006) 485-493
26. Nauck M.A., Heimesaat M.M., 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 91 (1993) 301-307
27. Meier J.J., Hücking K., Holst J.J., et al. Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes 50 (2001) 2497-2504
28. Turner R.C., Cull C.A., Stratton I.M., et al., UK Prospective Diabetes Study (UKPDS) Group. Overview of 6 years' therapy of type II diabetes: a progress disease (UKPDS 16). Diabetes 44 (1995) 1249-1258
29. Ferrannini E., Gastaldelli A., Miyazaki Y., Matsuda M., Mari A., and DeFronzo R.A. β-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 90 (2005) 493-500
30. Nauck M., Stöckmann F., Ebert R., and Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29 (1986) 46-52
31. Nauck M.A. Unraveling the science of incretin biology. Am J Med 122 suppl (2009) S3-S10
32. Gilbert M.P., and Pratley R.E. Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus. Am J Med 122 suppl (2009) S11-S24
33. Hollman R.R., Paul S.K., Bethel A., et al. 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359 (2008) 1577-1589
34. Hollman R.R., Paul S.K., Bethel A., et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 359 (2008) 1565-1576
35. American Diabetes Association. Position statement: standards of medical care in diabetes-2007. Diabetes Care 30 (2007) S4-S41
36. ACE/AACE Diabetes Road Map Task Force. Road maps to achieve glycemic control in type 2 diabetes mellitus. Endocr Pract 13 (2007) 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 32 suppl 1 (2008) S1-S201
38. Etzwiler D.D., Mazze R.S., and Bergenstal R.M. Diabetes translation: a blueprint for the future. Diabetes Care 17 suppl 1 (1994) 1-4
39. Mazze R.S., Etzwiler D.D., Strock E., et al. Staged diabetes management: toward an integrated model of diabetes care. Diabetes Care 17 suppl 1 (1994) 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 47 (1998) 127-132
41. Benjamin E.M., and Bradley R. Systematic implementation of customized guidelines: the staged diabetes management approach. J Clin Outcomes Manag 9 (2002) 81-86
42. Sidorov J.E., Harris R.E., Shull R.D., et al. Disease management for diabetes mellitus: impact on hemoglobin A1c. Am J Manag Care 6 (2000) 1217-1226
43. Sidorov J., Shull R., Tomcavage J., et al. Does diabetes disease management save money and improve outcomes?. Diabetes Care 25 (2002) 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 27 (2004) 110-115
45. Mazze R.S., Strock E., Simonson G.D., and Bergenstal R.M. Staged Diabetes Management: a Systematic Approach. 2nd ed (rev) (2006), John Wiley & Sons, Hoboken, NJ
46. Bergenstal R.M. Treatment models from the International Diabetes Center: advancing from oral agents to insulin therapy in type 2 diabetes. Endocr Pract 12 (2006) 98-104
47. Mazze R.S., Powers M.A., Wetzler H.P., and Ofstead C.L. Partners in advancing care and education solutions study: impact on processes and outcomes of diabetes care. Popul Health Manag 11 (2008) 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 321 (1989) 337-343
49. Polonsky K.S., Given B.D., Hirsch L.J., et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 318 (1988) 1231-1239
50. Weir G.C., and Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes 53 suppl 3 (2004) S16-S21
51. Nyström T., Gutniak M.K., 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 287 (2004) 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. Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California (2008) Oral Presentation 190
53. Mudaliar S., and Henry R.R. Incretin therapies: effects beyond glycemic control. Am J Med 122 suppl (2009) S25-S36
54. Fisman E.Z., Motro M., and Tenenbaum A. Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects. Adv Cardiol 45 (2008) 154-170
55. Misbin R.I., Green L., Stadel B.V., et al. Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338 (1998) 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 147 (2007) 386-399
57. Nissen S.E., and Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356 (2007) 2457-2471
58. Meier C., Kraenzlin M.E., Bodmer M., et al. Use of thiazolidinediones and fracture risk. Arch Intern Med 168 (2008) 820-825
59. Nielsen L.L., Young A.A., and Parkes D.G. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 117 (2004) 77-88
60. Byetta (exenatide) [package insert] (2007), Eli Lilly and Company, Indianapolis, IN
61. Buse J.B., Henry R.R., 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 27 (2004) 2628-2635
62. DeFronzo R.A., Ratner R.E., 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 28 (2005) 1092-1100
63. Kendall D.M., Riddle M.C., 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 28 (2005) 1083-1091
64. Klonoff D.C., Buse J.B., Nielsen L.L., 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 24 (2008) 275-286
65. Heine R.J., Van Gaal L.F., 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 143 (2005) 559-569
66. Nauck M.A., 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 50 (2007) 259-267
67. Barnett A.H., 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 29 (2007) 2333-2348
68. Bunck M.C., Diamant M.A., Corner E.B., et al. One year treatment with exenatide improves beta cell function and glycaemic control in metformin treated type 2 diabetes patients. 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 D.J., Buse J.B., 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 372 (2008) 1240-1250
70. Agersø H., Jensen L.B., Elbrønd B., et al. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 45 (2002) 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 373 (2009) 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 32 suppl (2008) 29
74. ®), a long-acting GLP-1 mimetic, in subjects with type 2 diabetes. Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California (2008) Abstract 519-P
75. Nauck M.A., Ratvier R.E., Kapitza C., Berria R., Boldrin M., and 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 13 (2007) 444-450
77. Davis S.N., 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 30 (2007) 2767-2772
78. Rosenstock J., and Fonseca V. Missing the point: substituting exenatide for nonoptimized insulin-going from bad to worse!. Diabetes Care 30 (2007) 2972-2973
79. Buse J.B., Klonoff D.C., Nielsen L.L., 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 29 (2007) 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 26 (2009) 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 32 (2009) 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. Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, CA (2008) Abstract 536-P
83. Russell-Jones D.S., 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. 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 E.J., 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 8 (2006) 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. 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. 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. 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 30 (2007) 1608-1610
89. Matthews D., Marre M., Le Thi T.D., et al. Liraglutide, a once-daily human GLP-1 analog, significantly improves β-cell function in subjects with type 2 diabetes. 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 D.A., Habener J.F., and 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 48 (1999) 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 143 (2002) 4397-4408
92. Buteau J., Foisy S., Rhodes C.J., et al. Protein kinase Czeta activation mediates glucagon-like peptide-1-induced pancreatic beta-cell proliferation. Diabetes 50 (2001) 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 30 (2007) 2032-2033
94. Fehse F., Trautmann M., Holst J.J., 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 90 (2005) 5991-5997
95. Degn K.B., Juhl C.B., 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 53 (2004) 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 25 (2008) 152-156
97. Chang A.M., 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 52 (2003) 1786-1791
98. Helleberg H., Malm-Erjefält M., Bjørnsdottir I., et al. Metabolism and excretion of [Pal-3H]-liraglutide in human healthy subjects. Program and Abstracts of the American Diabetes Association (ADA) 68th Sessions; June 6-10. San Francisco, California (2007) Abstract 2107-PO
99. Jacobsen L.V., Hindsberger C., Robson R., and Zdravkovic M. Pharmacokinetics of the long-acting human GLP-1 analogue liraglutide in subjects with renal impairment. 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., and Zdravkovic M. Influence of hepatic impairment on pharmacokinetics of the long-acting human GLP-1 analogue liraglutide. 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=91985 Accessed January 8, 2009
103. Noel R., Braun D., Patterson R., and Bloomgren G. Increased risk of acute pancreatitis observed in patients with type 2 diabetes. Program and Abstracts of the 24th International Conference on Pharmacoepidemiology and Therapeutic Risk Management; August 17-20. Copenhagen, Denmark (2008) Abstract 409
104. Blomgren K.B., Sundström A., Steineck G., and Wiholm B.E. Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. Diabetes Care 25 (2002) 298-302
105. De Santis A., Attili A.F., Ginanni Corradini S., et al. Gallstones and diabetes: a case-control study in a free-living population sample. Hepatology 25 (1997) 787-790
106. Toskes P.P. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am 19 (1990) 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.pdf Accessed November 7, 2008
108. Exenatide (marketed as BYETTA): acute pancreatitis [postmarketing review]. FDA Drug Safety Newsletter. Winter 1 (2008) 12-14. http://www.fda.gov/CDER/dsn/2008_winter/postmarketing.htm Accessed 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.htm Accessed 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 29 (2006) 2638-2643
111. Aschner P., Kipnes M.S., Lunceford J.K., 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 29 (2006) 2632-2637
112. Goldstein B.J., Feinglos M.N., Lunceford J.K., 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 30 (2007) 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 9 (2007) 733-745
114. Pi-Sunyer F.X., Schweizer A., Mills D., and Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes. Diabetes Res Clin Pract 76 (2007) 132-138
115. Rosenstock J., Kim S.W., Baron M.A., 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 9 (2007) 175-185
116. Bosi E., Camisasca R.P., 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 30 (2007) 890-895
117. Rosenstock J., Foley J.E., 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 31 (2008) 30-35
118. DeFronzo R.A., 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 24 (2008) 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 9 (2007) 186-193
120. Balas B., Baig M.R., 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 92 (2007) 1249-1255
121. Ahrén B., Pacini G., Foley J.E., and 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 28 (2005) 1936-1940
122. Mari A., Scherbaum W.A., Nilsson P.M., 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 93 (2008) 103-109
123. Ristic S., Byiers S., Foley J., and Holmes D. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab 7 (2005) 692-698
124. Januvia (sitagliptin) [package insert] (2007), Merck & Co., Inc, Whitehouse, Station, NJ
125. He Y.L. The influence of hepatic impairment on the pharmacokinetics of vildagliptin. Program and Abstracts of the American Diabetes Association (ADA) 66th Sessions; June 9-13. Washington, DC (2006) Abstract 2024-PO
126. ® annex I: summary of product characteristics. www.emea.europa.eu/humandocs/PDF/EPAR/galvus/H-771-PI-en.pdf Accessed 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.cms Accessed January 8, 2009
128. Nathan D.M., Cleary P.A., Backlund J.Y., 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 353 (2005) 2643-2653
129. Yamagishi S., Matsui T., and 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 71 (2008) 749-751