Glucagon-like peptide-1-based therapies: New developments and emerging data

Diabetes, Obesity and Metabolism

Volumn 10, Issue SUPPL. 3, 2008, Pages 22-35

  Garber, Alan J ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

GLP 1; Therapies; cell

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALOGLIPTIN; ANTIDIABETIC AGENT; DENAGLIPTIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLIMEPIRIDE; GLIPIZIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; INCRETIN; INSULIN; INSULIN ASPART; INSULIN GLARGINE; LIRAGLUTIDE; METFORMIN; ORAL ANTIDIABETIC AGENT; PEPTIDE HYDROLASE INHIBITOR; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN;

ABSENCE OF SIDE EFFECTS; ADD ON THERAPY; ANTIBODY PRODUCTION; AREA UNDER THE CURVE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIARRHEA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSAGE FORM COMPARISON; DRUG FORMULATION; DRUG HALF LIFE; DRUG INDICATION; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; GASTRITIS; GASTROINTESTINAL DISEASE; GLUCOSE HOMEOSTASIS; GLYCEMIC CONTROL; HORMONE ACTION; HORMONE RELEASE; HUMAN; HYPOGLYCEMIA; MONOTHERAPY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE DRUG DOSE; URINARY TRACT INFECTION; VOMITING; WEIGHT REDUCTION;

EID: 47649096171     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2008.00921.x     Document Type: Review

References (96)

1. Turner RC, Cull CA, Frighi V, Holman RR. The UK Prospective Diabetes Study 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.
2. UKPDS 16. UK prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: A progressive disease. UK Prospective Diabetes Study Group. Diabetes 1995; 44: 1249-1258.
3. Carver C. Insulin treatment and the problem of weight gain in type 2 diabetes. Diabetes Educ 2006; 32: 910-917.
4. Korytkowski M. When oral agents fail: Practical barriers to starting insulin. Int J Obes Relat Metab Disord 2002; 26 (Suppl. 3): S18-S24.
5. Anderson JW, Konz EC. Obesity and disease management: Effects of weight loss on comorbid conditions. Obes Res 2001; 9 (Suppl. 4): 326S-334S.
6. Anderson JW, Kendall CW, Jenkins DJ et al. Importance of weight management in type 2 diabetes: Review with meta-analysis of clinical studies. J Am Coll Nutr 2003; 22: 331-339.
7. Nauck M. GLP-1 in type 2 diabetes: The beta cell and beyond. Diabetes Obes Metab 2008; 10 (Suppl. 3): 2-13.
8. Nauck MA, Homberger E, Siegel EG et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986; 63: 492-498.
9. Holst J. The physiology and pharmacology of incretins in type 2 diabetes. Diabetes Obes Metab 2008; 10 (Suppl. 3): 14-21.
10. Edwards CM, Todd JF, Mahmoudi M et al. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes 1999; 48: 86-93.
11. Fehmann HC, Hering BJ, Wolf MJ et al. Effects of glucagon-like peptide-I (GLP-I) on hormone secretion from isolated human pancreatic islets. Pancreas 1995; 11: 196-200.
12. 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.
13. Nauck MA, Kleine N, Ørskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 741-744.
14. Vilsbøll T, Agerso H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003; 88: 220-224.
15. Exenatide (Byetta ®). SPC 20/11/06. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/byetta/H-698-PI-en.pdf. Accessed 13 September 2007.
16. Exenatide (Byetta ®). 2 October 2007. Available from URL: http://www.fda.gov/cder/foi/label/2007/021773s007lbl.pdf. Accessed 13 September 2007.
17. Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue from Heloderma suspectum venom. J Biol Chem 1992; 267: 7402-7405.
18. Kolterman O, Kim DD, Shen L et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am Health Syst Pharm 2005; 62: 173-181.
19. Nielsen L, Baron A. Pharmacology of exenatide (synthetic exendin-4) for the treatment of type 2 diabetes. Curr Opin Investig Drugs 2003; 4: 401-405.
20. Nielsen L, Young AA, Parkes DG et al. Pharmacology of exenatide (synthetic exendin-4): A potential therapeutic for improved glycaemic control of type 2 diabetes. Regul Pept 2004; 117: 77-88.
21. 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.
22. Christel C, DeNardo D. Absence of exendin-4 effects on postprandial glucose and lipids in the Gila monster, Heloderma suspectum. J Comp Physiol B 2007; 177: 129-134.
23. Buse J, Henry RR, Jan J et al. 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.
24. DeFronzo R, 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.
25. 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.
26. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2006; 29 (Suppl. 1): S1-S85.
27. Ratner RE, Maggs D, Nielsen LL et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab 2006; 8: 419-428.
28. 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.
29. 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.
30. 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.
31. Byetta ® (exenatide injection). Prescribing Information. San Diego California: Amylin Pharmaceuticals; 2007. AvHilable from URL: http://www.pi.lilly.com/us/byetta-pi.pdf. Accessed 8 October 2007.
32. Degn KB, Brock B, Juhl CB et al. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes 2004; 53: 2397-2403.
33. Zinman B, Hoogwerf BJ, Duran Garcia S 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. 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.
35. Heine RJ, Van Gaal LF, Johns D et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: A randomized trial. Ann Intern Med 2005; 143: 559-569.
36. Briceno RM, Lagari-Libhaber VS, Meneghini LF. Clinical observation study of the safety, effectiveness, and tolerability of exenatide in a real-world setting. Diabetes 2007; 56 (Suppl. 1): Abstract 2147-PO.
37. Loh JA, Clement SC. Efficacy of exenatide therapy over 12 months in a real world setting. Diabetes 2007; 56 (Suppl. 1): Abstract 0570-P.
38. Vilsbøll T. Liraglutide: A once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs 2007; 16: 231-237.
39. Drucker D, Nauck M. The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368: 1696-1701.
40. Elbrond B, Jakobsen G, Larsen S et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care 2002; 25: 1398-1404.
41. Agersø H, Jensen LB, Elbrond 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.
42. 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.
43. Madsbad S, Schmitz O, Ranstam J et al. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): A 12-week, double-blind, randomized, controlled trial. Diabetes Care 2004; 27: 1335-1342.
44. Feinglos MN, Saad MF, Pi-Sunyer FX et al. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with type 2 diabetes. Diabet Med 2005; 22: 1016-1023.
45. Harder H, Nielsen L, Tu DT, Astrup A. The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes. Diabetes Care 2004; 27: 1915-1921.
46. Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long-acting human GLP-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes mellitus. Diabetes Care 2007; 30: 1608-1610.
47. Mari A, Degn K, Brock B, Rungby J, Ferrannini E, Schmitz O. Characterisation of beta-cell function improvement by liraglutide: modelling analysis of 24-h tests. Diabetes 2006; 55 (Suppl. 1): A124 (Abstract 522-P).
48. Vilsbøll T, Brock B, Perrild H et al. Liraglutide, a once-daily human GLP-1 analogue improves beta-cell function and arginine stimulated insulin secretion at hyperglycaemia in patients with type 2 diabetes mellitus. Diabet Med 2008; 25: 152-156.
49. Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide treatment, blood pressure and biomarkers of cardiovascular risk in patients with type 2 diabetes: 14 weeks monotherapy study. Diabetes 2006; 55 (Suppl. 1): Abstract 2007-PO.
50. Nauck MA, Homspesch M, Filipczak R et al. Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes. Exp Clin Endocrinol Diabetes 2006; 114: 417-423.
51. Seino Y, Kaku K, Nishijima K et al. Once daily dosing of the long acting GLP-1 analog liraglutide significantly improves glycaemic control by reducing both fasting and post-prandial glucose levels in Japanese subjects with type 2 diabetes. Diabetes 2007; 56 (Suppl. 1): Abstract 0520-P.
52. Irie S, Matsumura Y, Zdravkovic M et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of once-daily GLP-1 analogue liraglutide in healthy Japanese subjects. Diabetes 2007; 56 (Suppl. 1): Abstract 2131-PO.
53. Zdravkovic M, Hale P, Le Thi TD, Kristensen P. Overview of the design of the phase 3 studies for the long-acting human GLP-1 analogue liraglutide: Liraglutide Effect and Action in Diabetes (LEAD). Diabetes 2007; 56 (Suppl. 1): Abstract 2251-PO.
54. LEAD (Liraglutide Effect and Action in Diabetes) programme. Available from URL: http://www.clinicaltrials.gov/ct/search;jsessionid= 94D11DA9EA798B6DFE42464680AD9F8?term=liraglutide. Accessed 21 September 2007.
55. Green BD, Flatt PR, Bailey CJ et al. Dipeptidyl peptidase IV (DPP IV) inhibitors: A newly emerging drug class for the treatment of type 2 diabetes. Diab Vasc Dis Res 2006; 3: 159-165.
56. Marguet D, Baggio L, Kobayashi T et al. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 2000; 97: 6874-6879.
57. Ahren B, Landin-Olsson M, Jansson PA et al. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 2078-2084.
58. Sitagliptin (Januvia ®). 16 October 2007. Available from URL: http://www.fda.gov/cder/foi/label/2006/021995lbl.pdf. Accessed 7 November 2007.
59. Herman GA, Stevens C, van Dyck K et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: Results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005; 78: 675-688.
60. Herman G, Bergman A, Stevens C et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab 2006; 91: 4612-4619.
61. Scott R, Wu M, Sanchez M et al. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract 2007; 61: 171-180.
62. Raz I, Hanefeld M, Xu L et al. Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006; 49: 2564-2571.
63. Aschner P, Kipnas MS, Luncefold 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.
64. Nonaka K, Kakikawa T, Sato A et al. Twelve-week efficacy and tolerability of sitagliptin, a dipeptidyl peptidase-IV inhibitor in Japanese patients with T2DM. Diabetes 2006; 55 (Suppl. 1): A129 (Abstract 537-P).
65. 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.
66. 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.
67. Nauck MA, Meininger G, Sheng D et al. Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: A randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007; 9: 194-205.
68. Goldstein BJ, Feinglos MN, Lunceford JK et al. 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.
69. Rosenstock J, Brazg R, Andrynk PJ et al. Sitagliptin Study 019 Group. 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.
70. Vildagliptin (Galvus ®). Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/galvus/H-771-PI-en.pdf. Accessed 7 November 2007.
71. 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.
72. Ristic S, Byiers S, Foley J, Holmes D et al. 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.
73. Pratley RE, Jauffret-Kamel S, Galbreath E, Holmes D. Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Horm Metab Res 2006; 38: 423-428.
74. Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetes. Diabetes Res Clin Pract 2007; 76: 132-138.
75. Dejager S, Razac S, Foley JE, Schweizer A. Vildagliptin in drug-naive patients with type 2 diabetes: A 24-week, double-blind, randomized, placebo-controlled, multiple-dose study. Horm Metab Res 2007; 39: 218-223.
76. 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.
77. 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.
78. 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.
79. Mimori N, Terao S, Holmes D. Vildagliptin improves glycemic control as evidenced by HbA1c after 12 weeks therapy in Japanese patients with type 2 diabetes. Diabetes 2006; 55 (Suppl. 1): A125 (Abstract 527-P).
80. Hanefeld M, Herman G, Mickel C et al. Effect of MK-0431, a dipeptidyl peptidase IV (DPP-IV) inhibitor on glycemic control after 12 weeks in patients with type 2 diabetes. Diabetologia 2005; 48 (Suppl. 1): 287 (Abstract 791).
81. Ahren 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.
82. Utzschneider KM, Tong J, Montgomery B et al. The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose. Diabetes Care 2008; 3: 108-113.
83. 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.
84. List J, Rosenstock J, Sankoh S, Chen R. Saxagliptin improves glycaemic control as monotherapy in type 2 diabetes. Diabetologia 2007; 50 (Suppl. 1): Abstract 0889.
85. DeFronzo RA, Hissa M, Blauwet MB, Chen RS. Saxagliptin added to metfomin improves glycemic control in patients with type 2 diabetes. Diabetes 2007; 56 (Suppl. 1): Abstract 0285-OR.
86. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endoc Pract 2007; 13 (Suppl. 1): 1-68.
87. Christopher R, Covington P, Davenport M et al. Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects. Clin Ther 2008; 30: 513-527.
88. Covington P, Christopher R, Davenport M et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: A randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther 2008; 30: 499-512.
89. Bose A, Mocanu MM, Carr RD, Brand CL, Yellon DM. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005; 54: 146-151.
90. Mari A, Sallas WM, He YL. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005; 90: 4888-4894.
91. Jonker D, Toft AD, Kristensen P, Knudsen L, Watson E. Pharmacokinetic modelling of the once-daily human GLP-1 analogue liraglutide in healthy volunteers and comparison to exenatide. Diabetes 2007; 56 (Suppl. 1): Abstract 0605-P.
92. Kolterman OG, Buse JB, Fineman MS. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 3082-3089.
93. Juhl CB, Hollingdal M, Sturis J. Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes 2002; 51: 424-429.
94. 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.
95. He Y, Wang Y, Bullock JM. Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT. J Clin Pharmacol 2007; 47: 633-641.
96. Mu J, Woods J, Zhou YP et al. Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic {beta}-cell mass and function in a rodent model of type 2 diabetes. Diabetes 2006; 55: 1695-1704.