Minimizing the risk of hypoglycemia with vildagliptin: Clinical experience, mechanistic basis, and importance in type 2 diabetes management

Diabetes Therapy

Volumn 2, Issue 2, 2011, Pages 51-66

  Dejager, Sylvie ^a   Schweizer, Anja ^b  

^a NOVARTIS PHARMA K K   (Japan)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

hypoglycemia; type 2 diabetes mellitus; vildagliptin

Indexed keywords

DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLICLAZIDE; GLIMEPIRIDE; GLIPIZIDE; GLITAZONE DERIVATIVE; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; INSULIN; METFORMIN; ORAL ANTIDIABETIC AGENT; PIOGLITAZONE; PLACEBO; SITAGLIPTIN; SULFONYLUREA DERIVATIVE; VILDAGLIPTIN;

ADD ON THERAPY; BALANCE DISORDER; BLOOD GLUCOSE MONITORING; CONFUSION; COST OF ILLNESS; DISEASE SEVERITY; DISORIENTATION; DRUG MEGADOSE; DRUG WITHDRAWAL; EARLY INTERVENTION; FRAIL ELDERLY; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; IMPAIRED GLUCOSE TOLERANCE; LOW DRUG DOSE; MALAISE; MONOTHERAPY; MORBIDITY; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PERSONAL EXPERIENCE; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; RISK REDUCTION; SYNCOPE; UNSTEADINESS; VERTIGO; VISUAL IMPAIRMENT;

EID: 79955931729     PISSN: 18696953     EISSN: 18696961     Source Type: Journal    
DOI: 10.1007/s13300-010-0018-0     Document Type: Review

References (84)

1. Amiel SA, Dixon T, Mann R, Jameson K. Hypoglycaemia in type 2 diabetes. Diabet Med. 2008; 25: 245-254.
2. Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care. 2010; 33: 1389-1394.
3. Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005; 28: 1245-1249.
4. Barnett AH. Avoiding hypoglycaemia while achieving good glycaemic control in type 2 diabetes through optimal use of oral agent therapy. Curr Med Res Opin. 2010; 26: 1333-1342.
5. Heller S, Chapman J, McCloud J, Ward J. Unreliability of reports of hypoglycaemia by diabetic patients. BMJ. 1995; 310: 440.
6. Wild D, von Maltzahn R, Brohan E, Christensen T, Clauson P, Gonder-Frederick L. A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education. Patient Educ Couns. 2007; 68: 10-15.
7. Alvarez GF, Tofe PS, Krishnarajah G, Lyu R, Mavros P, Yin D. Hypoglycaemic symptoms, treatment satisfaction, adherence and their associations with glycaemic goal in patients with type 2 diabetes mellitus: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAPDM) Study. Diabetes Obes Metab. 2008; 10(suppl. 1): 25-32.
8. Vexiau P, Mavros P, Krishnarajah G, Lyu R, Yin D. Hypoglycaemia in patients with type 2 diabetes treated with a combination of metformin and sulphonylurea therapy in France. Diabetes Obes Metab. 2008; 10(suppl. 1): 16-24.
9. Davis SN, Mann S, Briscoe VJ, Ertl AC, Tate DB. Effects of intensive therapy and antecedent hypoglycemia on counterregulatory responses to hypoglycemia in type 2 diabetes. Diabetes. 2009; 58: 701-709.
10. Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008; 57: 3169-3176.
11. Segel SA, Paramore DS, Cryer PE. Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. Diabetes. 2002; 51: 724-733.
12. Davis TM, Brown SG, Jacobs IG, Bulsara M, Bruce DG, Davis WA. Determinants of severe hypoglycemia complicating type 2 diabetes: the Fremantle diabetes study. J Clin Endocrinol Metab. 2010; 95: 2240-2247.
13. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007; 50: 1140-1147.
14. Leese GP, Wang J, Broomhall J, et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Diabetes Care. 2003; 26: 1176-1180.
15. Schernthaner G, Grimaldi A, Di Mario U, et al. GUIDE study: double-blind comparison of oncedaily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest. 2004; 34: 535-542.
16. Pi-Sunyer FX. The impact of weight gain on motivation, compliance, and metabolic control in patients with type 2 diabetes mellitus. Postgrad Med. 2009; 121: 94-107.
17. Stargardt T, Gonder-Frederick L, Krobot KJ, Alexander CM. Fear of hypoglycaemia: defining a minimum clinically important difference in patients with type 2 diabetes. Health Qual Life Outcomes. 2009; 7: 91.
18. Davis RE, Morrissey M, Peters JR, Wittrup-Jensen K, Kennedy-Martin T, Currie CJ. Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes. Curr Med Res Opin. 2005; 21: 1477-1483.
19. Lundkvist J, Berne C, Bolinder B, Jonsson L. The economic and quality of life impact of hypoglycemia. Eur J Health Econ. 2005; 6: 197-202.
20. Currie CJ, Morgan CL, Poole CD, Sharplin P, Lammert M, McEwan P. Multivariate models of health-related utility and the fear of hypoglycaemia in people with diabetes. Curr Med Res Opin. 2006; 22: 1523-1534.
21. Jonsson L, Bolinder B, Lundkvist J. Cost of hypoglycemia in patients with type 2 diabetes in Sweden. Value Health. 2006; 9: 193-198.
22. Allicar MP, Megas F, Houzard S, Baroux A, Le Thai F, Augendre-Ferrante B. Frequency and costs of hospital stays for hypoglycemia in France in 1995 [In French]. Presse Med. 2000; 29: 657-661.
23. Holstein A, Plaschke A, Egberts EH. Incidence and costs of severe hypoglycemia. Diabetes Care. 2002; 25: 2109-2110.
24. Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev. 2008; 24: 353-363.
25. Gill GV, Woodward A, Casson IF, Weston PJ. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes-the 'dead in bed' syndrome revisited. Diabetologia. 2009; 52: 42-45.
26. Landstedt-Hallin L, Englund A, Adamson U, Lins PE. Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus. J Intern Med. 1999; 246: 299-307.
27. Lindstrom T, Jorfeldt L, Tegler L, Arnqvist HJ. Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus. Diabet Med. 1992; 9: 536-541.
28. Adler GK, Bonyhay I, Failing H, Waring E, Dotson S, Freeman R. Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control. Diabetes. 2009; 58: 360-366.
29. Campbell I. Dead in bed syndrome: manifestation of nocturnal hypoglycaemia? Diabet Med. 1991; 8: 3-4.
30. Desouza C, Salazar H, Cheong B, Murgo J, Fonseca V. Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring. Diabetes Care. 2003; 26: 1485-1489.
31. Dandona P, Chaudhuri A, Dhindsa S. Proinflammatory and prothrombotic effects of hypoglycemia. Diabetes Care. 2010; 33: 1686-1687.
32. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010; 340: b4909.
33. Boyko EJ. ACCORD glycemia results continue to puzzle. Diabetes Care. 2010; 33: 1149-1150.
34. Bremer JP, Jauch-Chara K, Hallschmid M, Schmid S, Schultes B. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care. 2009; 32: 1513-1517.
35. Halimi S, Raccah D, Schweizer A, Dejager S. Role of vildagliptin in managing type 2 diabetes mellitus in the elderly. Curr Med Res Opin. 2010; 26: 1647-1656.
36. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP, Jr., Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009; 301: 1565-1572.
37. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359: 1577-1589.
38. Amiel SA, Cryer PE. Attenuated sympathoadrenal responses, but not severe hypoglycemia, during aggressive glycemic therapy of early type 2 diabetes. Diabetes. 2009; 58: 515-517.
39. Deacon CF. Incretin-based treatment of type 2 diabetes: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2007; 9(suppl. 1): 23-31.
40. Keating GM. Vildagliptin: a review of its use in type 2 diabetes mellitus. Drugs. 2010; 70: 2089-2112.
41. 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.
42. 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; 31: 108-113.
43. Scherbaum WA, Schweizer A, Mari A, et al. Efficacy and tolerability of vildagliptin in drug-naive patients with type 2 diabetes and mild hyperglycaemia. Diabetes Obes Metab. 2008; 10: 675-682.
44. Scherbaum WA, Schweizer A, Mari A, et al. Evidence that vildagliptin attenuates deterioration of glycaemic control during 2-year treatment of patients with type 2 diabetes and mild hyperglycaemia. Diabetes Obes Metab. 2008; 10: 1114-1124.
45. Rosenstock J, Baron MA, Dejager S, Mills D, Schweizer A. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Care. 2007; 30: 217-223.
46. 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.
47. 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.
48. Pan C, Yang W, Barona JP, et al. Comparison of vildagliptin and acarbose monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabet Med. 2008; 25: 435-441.
49. Goke B, Hershon K, Kerr D, et al. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naive patients with type 2 diabetes: comparison with metformin. Horm Metab Res. 2008; 40: 892-895.
50. Foley JE, Sreenan S. Efficacy and safety comparison between the DPP-4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug-naive patients with type 2 diabetes. Horm Metab Res. 2009; 41: 905-909.
51. 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.
52. Bosi E, Dotta F, Jia Y, Goodman M. Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2009; 11: 506-515.
53. Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Obes Metab. 2009; 11: 804-812.
54. Pratley RE, Rosenstock J, Pi-Sunyer FX, et al. Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care. 2007; 30: 3017-3022.
55. Schweizer A, Dejager S, Foley JE, Shao Q, Kothny W. Clinical experience with vildagliptin in the management of type 2 diabetes in a patient population ≥75 years: a pooled analysis from a database of clinical trials. Diabetes Obes Metab. 2011; 13: 55-64.
56. Bolli G, Dotta F, Colin L, Minic B, Goodman M. Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Obes Metab. 2009; 11: 589-595.
57. 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.
58. Filozof C, Gautier JF. A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone: a 52-week, randomized study. Diabet Med. 2010; 27: 318-326.
59. Goodman M, Thurston H, Penman J. Efficacy and tolerability of vildagliptin in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Horm Metab Res. 2009; 41: 368-373.
60. Ferrannini E, Fonseca V, Zinman B, et al. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Diabetes Obes Metab. 2009; 11: 157-166.
61. Matthews DR, Dejager S, Ahren B, et al. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study. Diabetes Obes Metab. 2010; 12: 780-789.
62. 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.
63. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. 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.
64. 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.
65. Garber AJ, Foley JE, Banerji MA, et al. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab. 2008; 10: 1047-1056.
66. Kikuchi M, Haneda M, Koya D, et al. Efficacy and tolerability of vildagliptin as an add-on to glimepiride in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2010; 89: 216-223.
67. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007; 9: 733-745.
68. de Heer J, Holst JJ. Sulfonylurea compounds uncouple the glucose dependence of the insulinotropic effect of glucagon-like peptide 1. Diabetes. 2007; 56: 438-443.
69. El Ouaghlidi A, Rehring E, Holst JJ, et al. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. J Clin Endocrinol Metab. 2007; 92: 4165-4171.
70. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004; 27: 2628-2635.
71. Marre M, Shaw J, Brandle M, et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med. 2009; 26: 268-278.
72. Ahren B, Holst JJ, Mari A. Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans. Diabetes Care. 2003; 26: 2860-2864.
73. Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol. 2009; 297: 127-136.
74. 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.
75. Fonseca V, Baron M, Shao Q, Dejager S. Sustained efficacy and reduced hypoglycemia during one year of treatment with vildagliptin added to insulin in patients with type 2 diabetes mellitus. Horm Metab Res. 2008; 40: 427-430.
76. Vilsboll T, Rosenstock J, Yki-Jarvinen H, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12: 167-177.
77. Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications. 2010; 24: 79-83.
78. Devendra D, Gohel B, Bravis V, et al. Vildagliptin therapy and hypoglycaemia in Muslim type 2 diabetes patients during Ramadan. Int J Clin Pract. 2009; 63: 1446-1450.
79. Cryer PE. Glucose counterregulation: prevention and correction of hypoglycemia in humans. Am J Physiol. 1993; 264: E149-E155.
80. Israelian Z, Szoke E, Woerle J, et al. Multiple defects in counterregulation of hypoglycemia in modestly advanced type 2 diabetes mellitus. Metabolism. 2006; 55: 593-598.
81. Fruehwald-Schultes B, Kern W, Oltmanns KM, et al. Metformin does not adversely affect hormonal and symptomatic responses to recurrent hypoglycemia. J Clin Endocrinol Metab. 2001; 86: 4187-4192.
82. Landstedt-Hallin L, Adamson U, Lins PE. Oral glibenclamide suppresses glucagon secretion during insulin-induced hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab. 1999; 84: 3140-3145.
83. Ahrén B, Schweizer A, Dejager S, et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab. 2009; 94: 1236-1243.
84. Foley JE, Ligueros-Saylan M, He YL, et al. Effect of vildagliptin on glucagon concentration during meals in patients with type 1 diabetes. Horm Metab Res. 2008; 40: 727-730.