New approaches to treating type 2 diabetes mellitus in the elderly: Role of incretin therapies

Drugs and Aging

Volumn 25, Issue 11, 2008, Pages 913-925

  Abbatecola, Angela M ^a   Maggi, Stefania ^b   Paolisso, Giuseppe ^a,c  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b CNR   (Italy)

^c VI Divisione di Medicina Interna   (Italy)

Author keywords

Acarbose, therapeutic use; Elderly; Exenatide, therapeutic use; Liraglutide, therapeutic use; Research and development; Sitagliptin, therapeutic use; Type 2 diabetes mellitus, treatment; Vildagliptin, therapeutic use

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACARBOSE; DENAGLIPTIN; EXENDIN 4; GLIPIZIDE; LIRAGLUTIDE; MEGLITINIDE; METFORMIN; MIGLITOL; PIOGLITAZONE; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN;

ABDOMINAL DISCOMFORT; AGING; COMORBIDITY; DIARRHEA; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MECHANISM; DRUG TOLERABILITY; FLATULENCE; GASTROINTESTINAL SYMPTOM; HUMAN; HYPOGLYCEMIA; LOW DRUG DOSE; MONOTHERAPY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; VOMITING; WEIGHT REDUCTION;

AGED; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; FEMALE; GLUCAGON-LIKE PEPTIDE 1; HUMANS; HYPOGLYCEMIC AGENTS; INCRETINS; MALE;

EID: 54549116998     PISSN: 1170229X     EISSN: None     Source Type: Journal    
DOI: 10.2165/0002512-200825110-00002     Document Type: Review

References (103)

1. Rosenstock J. Management of type 2 diabetes mellitus in the elderly: special considerations. Drugs Aging 2001; 18 (1): 31-44
2. US Census Bureau. American FactFinder: United States S0101. Age and sex: data set: 2006 American Community Survey [online]. Available from URL: http://factfinder.census.gov/servlet/STTable?._bm=y&-geo_id= 01000US&-qr_name=ACS_2006_EST_G00_S0101&-ds_name=ACS_2006_EST_G00_&- redoLog=false. [Accessed 2007 Oct 31]
3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care 1998; 21: 518-24
4. Gossain VV, Carella MJ, Rovner DR. Management of diabetes in the elderly: a clinical perspective. J Assoc Acad Minority Phys 1994; 5: 22-31
5. American Diabetes Association. Economic costs of diabetes in the U.S. in 2002. Diabetes Care 2003; 26: 917-32
6. Meneilly GS, Tessier D. Diabetes in elderly adults. J Gerontol A Biol Sci Med Sci 2001; 56 (1): M5-13
7. Meneilly GS. Diabetes. In: Evans JG, Williams TF, Beattie BL, et al., editors. Oxford textbook of geriatric medicine. 2nd ed. New York: Oxford University Press, 2000: 210-7
8. Damsgaard EM, Froland A, Jorgensen OD, et al. Microalbuminuria as a predictor of increased mortality in elderly people. BMJ 1990; 300: 297-8
9. Kempen JH, O'Colmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol 2004; 122 (4): 522-63
10. Lee PP, Feldman ZW, Ostermann J, et al. Longitudinal prevalence of major eye diseases. Arch Ophthalmol 2003; 121 (9): 1303-10
11. Cohen DL, Neil HAW, Thorogood M, et al. A population based study of the incidence of complications associated with type 2 diabetes in the elderly. Diabet Med 1991; 8: 928-33
12. Dornan TL, Peck GM, Dow JDC, et al. A community survey of diabetes in the elderly. Diabet Med 1992; 9: 860-5
13. Ingelsson E, Sundstrom J, Arnlov J, et al. Insulin resistance and risk of congestive heart failure. JAMA 2005; 294 (3): 334-41
14. Gregg EW, Yaffe K, Cauley JA, et al. Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch Intern Med 2000 Jan 24; 160 (2): 174-80
15. Haan MN, Shemanski L, Jagust WJ, et al. The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 1999; 282: 40-6
16. Knopman D, Boland LL, Mosley T, et al. Atherosclerosis Risk in Communities (ARIC) study investigators: cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001; 56: 42-8
17. Fontbonne A, Berr C, Ducimetiere P, et al. Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 2001; 24: 366-70
18. Ott A, Stolk RP, Hofman A, et al. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 1996; 39: 1392-7
19. Luchsinger JA, Tang M, Stern Y, et al. Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 2001; 154: 635-41
20. Biessels GJ, van der Heide LP, Kamal A, et al. Ageing and diabetes: implications for brain function. Eur J Pharmacol 2002; 441 (1-2): 1-14
21. Abbatecola AM, Rizzo MR, Barbieri M, et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology 2006; 67 (2): 235-40
22. Feil D, Weinreb J, Sultzer D. Psychiatric disorders and psychotropic medication use in elderly persons with diabetes. Ann Long Term Care 2006; 14 (7): 39-47
23. Maty SC, Fried LP, Volpato S, et al. Patterns of disability related to diabetes mellitus in older women. J Gerontol A Biol Sci Med Sci 2004; 59 (2): 148-53
24. Miller DK, Lui LY, Perry 3rd HM, et al. Reported and measured physical functioning in older inner-city diabetic African Americans. J Gerontol A Biol Sci Med Sci 1999; 54 (5): M230-6
25. Gregg EW, Mangione CM, Cauley JA, et al. Diabetes and incidence of functional disability in older women. Diabetes Care 2002; 25: 61-7
26. Schwartz AV, Sellmeyer DE, Ensrud KE, et al. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 2001; 86: 32-8
27. Volpato S, Leveille SG, Blaum C, et al. Risk factors for falls in older disabled women with diabetes: the Women's Health and Aging Study. J Gerontol A Biol Sci Med Sci 2005; 60 (12): 1539-45
28. Gregg EW, Beckles GL, Williamson DF, et al. Diabetes and physical disability among U.S. adults. Diabetes Care 2000; 23: 1272-7
29. Brown JS, Vittinghoff E, Lin F, et al. Prevalence and risk factors for urinary incontinence in women with type 2 diabetes and impaired fasting glucose: findings from the National Health and Nutrition Examination Survey (NHANES) 2001-2002. Diabetes Care 2006; 29 (6): 1307-12
30. Fried LP, Tangen CM, Walston J, et al. Cardiovascular Health Study Collaborative Research Group: frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56 (3): M146-56
31. Rockwood K, Hogan DB, MacKnight C. Conceptualisation and measurement of frailty in elderly people. Drugs Aging 2000; 17 (4): 295-302
32. Vanitallie TB. Frailty in the elderly: contributions of sarcopenia and visceral protein depletion. Metabolism 2003; 52 (10 Suppl. 2): 22-6
33. Cigolle CT, Langa KM, Kabeto MU, et al. Geriatric conditions and disability: the Health and Retirement Study. Ann Intern Med 2007; 147 (3): 156-64
34. Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 2002; 162 (20): 2333-41
35. Baumgartner RN, Wayne SJ, Waters DL, et al. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res 2004; 12 (12): 1995-2004
36. Wolff JL, Starfield B, Anderson G. Prevalence, expenditures, and complications of multiple chronic conditions in the elderly. Arch Intern Med 2002; 162 (20): 2269-76
37. Shorr RI, Ray WA, Daugherty JR, et al. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157: 1681-6
38. Inzucchi SE, McGuire DK. New drugs for the treatment of diabetes: part II. Incretin-based therapy and beyond. Circulation 2008 Jan 29; 117 (4): 574-84
39. Mathieu C, Bollaerts K. Antihyperglycaemic therapy in elderly patients with type 2 diabetes: potential role of incretin mimetics and DPP-4 inhibitors. Int J Clin Pract Suppl Aug 2007; (154): 29-37
40. Gallwitz B. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. Treat Endocrinol 2005; 4 (6): 361-70
41. Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagon-like peptide-1 7-36 amide on glucagon-like peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes 1993; 42: 658-61
42. Drucker DJ, Nauck M. The incretin system: glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368: 1696-705
43. MacDonald PE, El-Kholy W, Riedel MJ, et al. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes 2002; 51 Suppl. 3: S434-42
44. List JF, Gabener JF. Glucagon-like peptide 1 agonists and the development and growth of pancreatic beta cells. Am J Physiol Endocrinol Metab 2004; 266: E875-81
45. Brubaker PL, Drucker DJ. Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 2004; 145: 2653-9
46. Meier JJ, Hucking 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: 2497-504
47. Gutniak M, Orskov C, Holst JJ, et al. Antidiabetogenic effect of glucagon-like peptide-1 [7-36]amide in normal subjects and patients with diabetes mellitus. New Engl J Med 1992; 326: 1316-22
48. Nathan DM, Schreiber E, Fogel H, et al. Insulinotropic action of glucagon-like peptide I-[7-37] in diabetic and nondiabetic subjects. Diabetes Care 1992; 15: 270-6
49. Meneilly GS, Greig N, Tidesley H, et al. Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care 2003; 26: 2835-41
50. Meneilly GS, Mcintosh CH, Pederson RA, et al. Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes. Diabetes Care 2001; 24: 1951-6
51. Meneilly GS, McIntosh CH, Pederson RA, et al. Glucagon-like peptide-1 [7-37] augments insulin release in elderly patients with diabetes. Diabetes Care 2001; 24: 964-5
52. Meneilly GS, Mcintosh CH, Pederson RA, et al. Glucagon-like peptide-1 [7-37] augments insulin-mediated glucose uptake in elderly patients with diabetes. J Gerontol A Biol Sci Med Sci 2001; 56: M681-5
53. Nauck MA, Heimesaat MM, Behle K, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 2002; 87: 1239-46
54. Nikolaidis LA, Elahi D, Hentosz T, et al. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 2004; 110: 955-61
55. Nikolaidis LA, Doverspike A, Hentosz T, et al. Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 2005; 312 (1): 303-8 56.
56. Nystrom 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: E1209-15
57. During MJ, Lei C, Zuzga DS, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003; 9 (9): 1173-9
58. Kolterman OG, Kim DD, Shen L, et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm 2005; 62: 173-81
59. Buse JB, Henry RR, Han 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 (11): 2628-35
60. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in patients with type 2 diabetes. Diabetes Care 2005; 28 (5): 1092-100
61. 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 (5): 1083-91
62. Cvetković RS, Plosker GL. Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs 2007; 67 (6): 935-54
63. 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: 559-69
64. 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: 259-67
65. 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 release in patients with type 2 diabetes. Diabetes 2004; 53 (5): 1187-94
66. 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 (6): 1335-42
67. Visbøll T, Zdravkovic M, Le-Thi T, et al. Liraglutide significantly improves glycemic control and lowers body weight without risk of either major or minor hypoglycemic episodes in subjects with type 2 diabetes [abstract no. 115-OR]. Diabetes 2006; 55 Suppl. 1: 27-8
68. Vilsbøll T. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs 2007; 16: 231-7
69. Feinglos MN, Saad MF, Pi-Sunyer FX, et al. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycemic control and bodyweight in subjects with type 2 diabetes. Diabet Med 2005; 22: 1016-23
70. Harder H, Nielsen L, Tu DT, et al. 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: 1915-21
71. Unger RH. Alpha- and beta-cell interrelationships in health and disease. Metabolism 1974; 23: 581-93
72. Lyseng-Williamson KA. Sitagliptin. Drugs 2007; 67 (4): 587-97
73. Hanefeld M, Herman G, Mickel C, et al. Effect of MK-0431, a dipeptidyl peptidase IV inhibitor, on glycemic control after 12 weeks in patients with type 2 diabetes [abstract no. 791]. Diabetologia 2005; 48 Suppl. 1: A287
74. 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: 171-80
75. Nonaka K, Kakikawa T, Sato A, et al. Twelve-week efficacy and tolerability of sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4), in Japanese patients with type 2 diabetes [abstract no. 0038]. Diabetologia 2006; 49 Suppl. 1: 25-6
76. Raz I, Hanefeld M, Xu L, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006; 49: 2564-71
77. Aschner P, Kipnes MS, Lunceford JK, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006; 29: 2632-7
78. Chan JC, Scott R, Arjona Ferreira JC, et al. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 2008; 10 (7): 545-55
79. Brazg R, Xu L, Dalla Man C, et al. Effect of adding sitagliptin, a dipeptidyl peptidase-4 inhibitor, to metformin on 24-h glycemic control and β-cell function in patients with type 2 diabetes. Diabetes Obes Metab 2007; 9: 186-93
80. Rosenstock J, Brazg R, Andryuk PJ, et al. Efficacy and safety of the dipeptidyl dipeptidase-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: 1556-68
81. Charbonnel B, Karasik A, Liu J, et al. 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: 2638-43
82. Nauck MA, Meininger G, Sheng D, et al. 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
83. Kleppinger EL, Helms K. The role of vildagliptin in the management of type 2 diabetes. Ann Pharmacother 2007; 41: 824-32
84. 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 (4): 1249-55
85. Ahrén B, Gomis R, Standl E, et al. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2874-80
86. Dejager S, Lebeaut A, Couturier A, et al. Sustained reduction in HbA1c during one-year treatment with vildagliptin in patients with type 2 diabetes (T2DM) [abstract no. 120-OR]. Diabetes 2006; 55 Suppl. 1: 29
87. 1c but without weight gain in drug-naive patients with type 2 diabetes (T2DM) [abstract no. 557-P]. Diabetes 2006; 55 Suppl. 1: 133
88. Garber A, Camisasca RP, Ehrsam E, et al. Vildagliptin added to metformin improves glycemic control and may mitigate metformin-induced GI side effects in patients with type 2 diabetes (T2DM) [abstract no. 121-OR]. Diabetes 2006; 55 Suppl. 1: 29
89. Pratley RE, Rosenstock J, Pi-Sunyer F-X, et al. Management of type 2 diabetes in treatment naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care 2007; 30 (12): 3017-22
90. Pratley RE, Rosenstock J, Pi-Sunyer FX, et al. Benefit/risk assessment of vildagliptin in the elderly: pooled analysis of 5 monotherapy studies [abstract]. Diabetes 2007; 56 Suppl. 1: A135
91. He Y-L, Sabo R, Campestrini J, et al. The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers. Br J Clin Pharmacol 2008; 65 (3): 338-46
92. Baron MA, Schweizer A, Couturier A, et al. Efficacy and tolerability of the DPP-4 inhibitor vildagliptin in drug naive patients with type 2 diabetes aged 65 years and older. J Am Geriatr Soc 2007; 55 Suppl.: 25-6
93. Augeri DJ, Robl JA, Betebenner DA, et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005; 48: 5025-37
94. Demuth HU, McIntosh CH, Pederson RA. Type 2 diabetes: therapy with dipeptidyl peptidase IV inhibitors. Biochim Biophys Acta 2005; 1751: 33-44
95. Qualmann C, Nauck MA, Holst JJ, et al. Glucagon-like peptide 1 [7-36 amide] secretion in response to luminal sucrose from the upper and lower gut: a study using alpha-glucosidase inhibition (acarbose). Scand J Gastroenterol 1995; 30: 892-6
96. Enç FY, Imeryüz N, Akin L, et al. Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release. Am J Physiol Gastrointest Liver Physiol 2001; 281: G752-63
97. Seifarth C, Bergmann J, Holst JJ, et al. Prolonged and enhanced secretion of glucagon-like peptide 1 [7-36 amide] after oral sucrose due to alpha-glucosidase inhibition (acarbose) in type 2 diabetic patients. Diabet Med 1998; 15: 485-91
98. Lee A, Patrick P, Wishart J, et al. The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics. Diabetes Obes Metab 2002; 4: 329-35
99. Hücking K, Kostic Z, Pox C, et al. α-Glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 [7-36 amide] and to delay gastric emptying in type 2 diabetic patients. Diabet Metab 2005; 22: 470-6
100. Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1-year randomized double-blind study. Diabetes Care 1998; 21: 1288-94
101. Damci T, Yalin S, Balci H, et al. Orlistat augments postprandial increases in glucagon-like peptide 1 in obese type 2 diabetic patients. Diabetes Care 2004; 27: 1077-80
102. DeLeon MJ, Chandurkar V, Albert SG, et al. Glucagon-like peptide-1 response to acarbose in elderly type 2 diabetic subjects. Diabetes Res Clin Pract 2002; 56: 101-6
103. Garber AJ, Foley JE, Banerji MA, et al. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with suphonylurea. Diabetes Obes Metab. Epub 2008 Feb 18