Initial combination therapy for type 2 diabetes mellitus: Is it ready for prime time?

American Journal of Medicine

Volumn 124, Issue 1 SUPPL., 2011, Pages

  Zinman, Bernard ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Combination therapy; Incretin based therapy; Type 2 diabetes mellitus

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALOGLIPTIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLIBENCLAMIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 AGONIST; INCRETIN; INSULIN ASPART; LIRAGLUTIDE; METFORMIN; METFORMIN PLUS ROSIGLITAZONE; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ACUTE PANCREATITIS; ARTICLE; CARDIOVASCULAR DISEASE; DIABETES CONTROL; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; GASTROINTESTINAL SYMPTOM; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; SIDE EFFECT; WEIGHT GAIN; WEIGHT REDUCTION;

BLOOD GLUCOSE; COMBINED MODALITY THERAPY; DIABETES MELLITUS, TYPE 2; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; LIFE STYLE;

EID: 78650720971     PISSN: 00029343     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.amjmed.2010.11.003     Document Type: Article

References (189)

1. S. Wild, G. Roglic, A. Green, R. Sicree, and H. King Global prevalence of diabetes: estimates for the year 2000 and projections for 2030 Diabetes Care 27 2004 1047 1053
2. Centers for Disease Control and Prevention (CDC) National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, 2008 http://www.cdc.gov/diabetes/pubs/pdf/ndfs- 2007.pdf Accessed August 23, 2010
3. Centers for Disease Control and Prevention (CDC) Prevalence of overweight and obesity among adults with diagnosed diabetesUnited States, 1988-1994 and 1999-2002 MMWR Morb Mortal Wkly Rep 53 2004 1066 1068
4. P.A. Daly, and L. Landsberg Hypertension in obesity and NIDDM Role of insulin and sympathetic nervous system Diabetes Care 14 1991 240 248
5. J.B. Buse, H.N. Ginsberg, G.L. Bakris American Heart Association and the American Diabetes Association Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association Diabetes Care 30 2007 162 172
6. B.B. Dokken The pathophysiology of cardiovascular disease and diabetes: beyond blood pressure and lipids Diabetes Spectr 21 2008 160 165
7. I.M. Stratton, A.I. Adler, and H.A. Neil Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study BMJ 321 2000 405 412
8. G.K. Booth, M.K. Kapral, K. Fung, and J.V. Tu Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study Lancet 368 2006 29 36
9. A. Norhammar, A. Tenerz, and G. Nilsson Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study Lancet 359 2002 2140 2144
10. M. Lankisch, R. Fth, and H. Glker Screening for undiagnosed diabetes in patients with acute myocardial infarction Clin Res Cardiol 97 2008 753 759
11. R.A. DeFronzo Pathogenesis of NIDDM: a balanced overview Diabetes Care 15 1992 318 368
12. M. Stumvoll, B.J. Goldstein, and T.W. van Haeften Type 2 diabetes: principles of pathogenesis and therapy Lancet 365 2005 1333 1346
13. L. Fritsche, C. Weigert, and H.U. Haring How insulin receptor substrate proteins regulate the metabolic capacity of the liverimplications for health and disease Curr Med Chem 15 2008 1316 1329
14. S.E. Kahn The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes Diabetologia 46 2003 3 19
15. M. Bjornholm, and J.R. Zierath Insulin signal transduction in human skeletal muscle: identifying the defects in type II diabetes Biochem Soc Trans 33 pt 2 2005 354 357
16. Y. Lin, and Z. Sun Current views on type 2 diabetes J Endocrinol 204 2010 1 11
17. M.A. Nauck, M.M. Heimesaat, C. Orskov, J.J. Holst, R. Ebert, and W. Creutzfeldt 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
18. M.A. Nauck, B. Baller, and J.J. Meier Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes Diabetes 53 suppl 3 2004 S190 S196
19. R. Pratley Islet dysfunction: an underlying defect in the pathophysiology of type 2 diabetes Endocrinol Metab Clin North Am 35 suppl 1 2006 6 11
20. H. Bays, L. Mandarino, and R.A. DeFronzo Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach J Clin Endocrinol Metab 89 2004 463 478
21. R.P. Robertson, J. Harmon, P.O. Tran, and V. Poitout β-Cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes Diabetes 53 suppl 1 2004 S119 S124
22. J.C. Beard, W.K. Ward, J.B. Halter, B.J. Wallum, and D. Porte Jr. Relationship of islet function to insulin action in human obesity J Clin Endocrinol Metab 65 1987 59 64
23. B. Balkau, A. Forhan, and E. Eschwge Two hour plasma glucose is not unequivocally predictive for early death in men with impaired fasting glucose: more results from the Paris Prospective Study Diabetologia 45 2002 1224 1230
24. M.Y. Donath, J.A. Ehses, and K. Maedler Mechanisms of beta-cell death in type 2 diabetes Diabetes 54 suppl 2 2005 S108 S113
25. G.C. Weir, and S. Bonner-Weir Five stages of evolving β-cell dysfunction during progression to diabetes Diabetes 53 suppl 3 2004 S16 S21
26. S.L. Aronoff, K. Berkowitz, B. Shreiner, and L. Want Glucose metabolism and regulation: beyond insulin and glucagon Diabetes Spectr 17 2004 183 190
27. C. Orskov, A. Wettergren, and J.J. Holst Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day Scand J Gastroenterol 31 1996 665 670
28. H.C. Fehmann, R. Goke, and B. Goke Cell and molecular biology of incretin hormones glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide Endocr Rev 16 1995 390 410
29. T. Vilsboll, and J.J. Holst Incretins, insulin secretion and type 2 diabetes mellitus Diabetologia 47 2004 357 366
30. 1c control among US adults with type 2 diabetes: NHANES 1999-2004 Curr Med Res Opin 25 2009 1605 1613
31. Canadian Diabetes Association Clinical practice guidelines for the prevention and management of diabetes in Canada2008 http://www.diabetes.ca/ files/cpg2008/cpg-2008.pdf Accessed August 23, 2010
32. E.S. Kilpatrick, A.K. Das, C. Orskov, and K. Berntorp Good glycaemic control: an international perspective on bridging the gap between theory and practice in type 2 diabetes Curr Med Res Opin 24 2008 2651 2661
33. K.L. Ong, B.M. Cheung, L.Y. Wong, N.M. Wat, K.C. Tan, and K.S. Lam Prevalence, treatment, and control of diagnosed diabetes in the U.S. National Health and Nutrition Examination Survey 1999-2004 Ann Epidemiol 18 2008 222 229
34. UK Prospective Diabetes Study Group UK Prospective Diabetes Study 16 Overview of 6 years' therapy of type II diabetes: a progressive disease Diabetes 44 1995 1249 1258
35. S.E. Kahn, S.M. Haffner, M.A. Heise ADOPT Study Group Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy N Engl J Med 355 2006 2427 2443
36. J. Levy, A.B. Atkinson, P.M. Bell, D.R. McCance, and D.R. Hadden Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study Diabet Med 15 1998 290 296
37. M.N. Cook, C.J. Girman, P.P. Stein, C.M. Alexander, and R.R. Holman Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes Diabetes Care 28 2005 995 1000
38. A.E. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, R.A. Rizza, and P.C. Butler β-Cell deficit and increased β-cell apoptosis in humans with type 2 diabetes Diabetes 52 2003 102 110
39. R. Cooper, J. Cutler, and P. Desvigne-Nickens Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: findings of the national conference on cardiovascular disease prevention Circulation 102 2000 3137 3147
40. C.S. Fox, S. Coady, and P.D. Sorlie Trends in cardiovascular complications of diabetes JAMA 292 2004 2495 2499
41. G. Danaei, C.M. Lawes, S. Vander Hoorn, C.J. Murray, and M. Ezzati Global and regional mortality from IHD and stroke attributable to higher-than-optimum blood glucose concentration: comparative risk assessment Lancet 368 2006 1651 1659
42. K.K. Ray, S.R. Seshasai, and S. Wijesuriya Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials Lancet 373 2009 1765 1772
43. American Diabetes Association Standards of medical care in diabetes2010 Diabetes Care 33 suppl 1 2010 S11 S61
44. D.M. Nathan, J.B. Buse, M.B. Davidson European Association for the Study of Diabetes Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes Diabetologia 52 2009 17 30
45. H.W. Rodbard, L. Blonde, S.S. Braithwaite AACE Diabetes Mellitus Clinical Practice Guidelines Task Force American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus Endocrinol Pract 13 suppl 1 2007 3 68
46. IDF Clinical Guidelines Task Force Global guideline for type 2 diabetes Brussels: International Diabetes Federation, 2005 http://www.idf.org/webdata/ docs/IDF%20GGT2D.pdf Accessed August 23, 2010
47. National Institute for Health and Clinical Excellence Type 2 diabetes: national clinical guideline for management in primary and secondary care (update) http://www.nice.org.uk/nicemedia/pdf/CG66diabetesfullguideline.pdf Accessed August 23, 2010
48. B.R. Shah, J.E. Hus, A. Laupacis, B. Zinman, and C. van Walraven Clinical inertia in response to inadequate glycemic control Diabetes Care 28 2005 600 606
49. D.C. Ziemer, C.D. Miller, and M.K. Rhee Clinical inertia contributes to poor diabetes control in a primary care setting Diabetes Educ 31 2005 564 571
50. M. Peyrot, R.R. Rubin, T. Lauritzen International DAWN Advisory Panel Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study Diabetes Care 28 2005 2673 2679
51. J.B. Brown, and G.A. Nichols Slow response to loss of glycemic control in type 2 diabetes mellitus Am J Manag Care 9 2003 213 217
52. J. Belsey, and G. Krishnarajah Glycaemic control and adverse events in patients with type 2 diabetes treated with metformin + sulphonylurea: a meta-analysis Diabetes Obes Metab 10 suppl 1 2008 1 7
53. D. Einhorn, M. Rendell, J. Rosenzweig, J.W. Egan, A.L. Mathisen, R.L. Schneider Pioglitazone 027 Study Group Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study Clin Ther 22 2000 1395 1409
54. A. Hamann, J. Garcia-Puig, G. Paul, J. Donaldson, and M. Stewart Comparison of fixed-dose rosiglitazone/metformin combination therapy with sulphonylurea plus metformin in overweight individuals with type 2 diabetes inadequately controlled on metformin alone Exp Clin Endocrinol Diabetes 116 2008 6 13
55. G. Bakris, M. Hill, and G. Mancia Achieving blood pressure goals globally: five core actions for health-care professionals A worldwide call to action J Hum Hypertens 22 2008 63 70
56. M.H. Weinberger, R.D. Glazer, N.A. Crikelair, and Y.T. Chiang Achieving blood pressure goal: initial therapy with valsartan/hydrochlorothiazide combination compared with monotherapy J Hum Hypertens 24 12 2010 823 830
57. P.D. Feldman, G.Y. Zou, C.J. Wong, M.K. Vandervoort, S.A.E. Nelson, and B.G. Feagan A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial Hypertension 53 2009 646 653
58. K.A. Couville, and H. Ventura Hypertension and heart failure: diagnosis and management Curr Hypertens Rep 8 2006 185 190
59. J.R. Sowers, G. Lastra, R. Rocha, Y. Seifu, N. Crikelair, and D.G. Levy Initial combination therapy compared with monotherapy in diabetic hypertensive patients J Clin Hypertens (Greenwich) 10 2008 668 676
60. M. Leoncini, A. Toso, and M. Maioli Effects of tirofiban plus clopidogrel versus clopidogrel plus provisional abciximab on biomarkers of myocardial necrosis in patients with non-ST-elevation acute coronary syndromes treated with early aggressive approach: results of the CLOpidogrel, upstream Tirofiban, in cath Lab Downstream Abciximab (CLOTILDA) study Am Heart J 150 2005 401
61. M.L. Hetland, K. Stengaard-Pedersen, and P. Junker Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study Ann Rheum Dis 67 2008 815 822
62. World Health Organization Rapid advice: antiretroviral therapy for HIV infection in adults and adolescentsSwitzerland, 2009 http://www.who.int/hiv/pub/ arv/rapid-advice-art.pdf Accessed August 23, 2010
63. M. de Boer, C.H. van Deurzen, and J.A. van Dijck Micrometastases or isolated tumor cells and the outcome of breast cancer N Engl J Med 361 2009 653 663
64. M.I. Harris, R. Klein, T.A. Welborn, and M.W. Knuiman Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis Diabetes Care 15 1992 815 819
65. A. Bagust, and S. Beale Deteriorating beta-cell function in type 2 diabetes: a long-term model QJM 96 2003 281 288
66. R.A. DeFronzo From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus [Banting lecture] Diabetes 58 2009 773 795
67. S. Colagiuri, C.A. Cull, R.R. Holman UKPDS Group Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes? UK Prospective Diabetes Study 61 Diabetes Care 25 2002 1410 1417
68. A. Festa, K. Williams, A.J. Hanley, and S.M. Haffner β-Cell dysfunction in subjects with impaired glucose tolerance and early type 2 diabetes: comparison of surrogate markers with first-phase insulin secretion from an intravenous glucose tolerance test Diabetes 57 2008 1638 1644
69. A.E. Kitabchi, M. Temprosa, W.C. Knowler Diabetes Prevention Program Research Group Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin Diabetes 54 2005 2404 2414
70. M. Karaca, C. Magnan, and C. Kargar Functional pancreatic beta-cell mass: involvement in type 2 diabetes and therapeutic intervention Diabetes Metab 35 2009 77 84
71. C.J. Rhodes Type 2 diabetesa matter of β-cell life and death Science 307 2005 380 384
72. M.K. Lingohr, R. Buettner, and C.J. Rhodes Pancreatic β-cell growth and survivala role in obesity-linked type 2 diabetes? Trends Mol Med 8 2002 375 384
73. S.A. Chang, H.S. Kim, and K.H. Yoon Body mass index is the most important determining factor for the degree of insulin resistance in non-obese type 2 diabetic patients in Korea Metabolism 53 2004 142 146
74. J.J. Meier The contribution of incretin hormones to the pathogenesis of type 2 diabetes Best Prac Res Clin Endocrinol Metab 23 2009 433 441
75. M. Nauck, F. Stckmann, R. Ebert, and W. Creutzfeldt Reduced incretin effect in type 2 (non-insulin-dependent) diabetes Diabetologia 29 1986 46 52
76. S. Del Prato Role of glucotoxicity and lipotoxicity in the pathophysiology of type 2 diabetes mellitus and emerging treatment strategies Diabet Med 26 2009 1185 1192
77. M.N. Cook, C.J. Girman, P.P. Stein, and C.M. Alexander Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with type 2 diabetes in UK primary care Diabet Med 24 2007 350 358
78. V.A. Fonseca Identification and treatment of prediabetes to prevent progression to type 2 diabetes Clin Cornerstone 9 2008 51 59
79. A. Ramachandran, C. Snehalatha, S. Mary, B. Mukesh, A.D. Bhaskar, and V. Vijay Indian Diabetes Prevention Programme (IDPP) The Indian Diabetes Prevention Programme Shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1) Diabetologia 49 2006 289 297
80. J. Tuomilehto, J. Lindstrm, J.G. Eriksson Finnish Diabetes Prevention Study Group Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance N Engl J Med 344 2001 1343 1350 (Pubitemid 32378388)
81. X.R. Pan, G.W. Li, and Y.H. Hu Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and Diabetes Study Diabetes Care 20 1997 537 544
82. K.S. Dale, J.I. Mann, K.A. McAuley, S.M. Williams, and V.L. Farmer Sustainability of lifestyle changes following an intensive lifestyle intervention in insulin resistant adults: follow-up at 2-years Asia Pac J Clin Nutr 18 2009 114 120
83. M.L. Jehn, M.R. Patt, L.J. Appel, and E.R. Miller III One year follow-up of overweight and obese hypertensive adults following intensive lifestyle therapy J Hum Nutr Diet 19 2006 349 354
84. H.C. Gerstein, S. Yusuf, J. Bosch DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial Lancet 368 2006 1096 1105
85. T.A. Buchanan, A.H. Xiang, and R.K. Peters Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women Diabetes 51 2002 2796 2803
86. J.L. Chiasson Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial Endocr Pract 12 suppl 1 2006 25 30
87. B. Zinman, S.B. Harris, and J. Neuman Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study Lancet 376 2010 103 111
88. J. Weng, Y. Li, and W. Xu Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial Lancet 371 2008 1753 1760
89. R. Retnakaran, N. Yakubovich, Y. Qi, C. Opsteen, and B. Zinman The response to short-term intensive insulin therapy in type 2 diabetes Diabetes Obes Metab 12 2010 65 71
90. G. Roman, and N. Hancu Early insulin treatment to prevent cardiovascular disease in prediabetes and overt diabetes Horm Metab Res 4 2009 116 122
91. M. Massi-Benedetti Changing targets in the treatment of type 2 diabetes Curr Med Res Opin 22 suppl 2 2006 S5 S13
92. P.C. Deedwania, and V.A. Fonseca Diabetes, prediabetes, cardiovascular risk: shifting the paradigm Am J Med 118 2005 939 947
93. K. Cusi, A. Consoli, and R.A. DeFronzo Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus J Clin Endocrinol Metab 81 1996 4059 4067
94. R.S. Hundal, M. Krssak, and S. Dufour Mechanism by which metformin reduces glucose production in type 2 diabetes Diabetes 49 2000 2063 2069
95. M. Lehtovirta, B. Forsn, and M. Gullstrm Metabolic effects of metformin in patients with impaired glucose tolerance Diabet Med 18 2001 578 583
96. M.J. Davies Insulin secretagogues Curr Med Res Opin 18 suppl 1 2002 S22 S30
97. A.J. Garber, J. Larsen, S.H. Schneider, B.A. Piper, D. Henry Glyburide/Metformin Initial Therapy Study Group Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes Diabetes Obes Metab 4 2002 201 208
98. A.J. Garber, D.S. Donovan Jr, P. Dandona, S. Bruce, and J.S. Park Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes J Clin Endocrinol Metab 88 2003 3598 3604
99. U. Panten, M. Schwanstecher, and C. Schwanstecher Sulfonylurea receptors and mechanism of sulfonylurea action Exp Clin Endocrinol Diabetes 104 1996 1 9
100. A.D. Rao, N. Kuhadiya, K. Reynolds, and V.A. Fonseca Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all-cause mortality? A meta-analysis of observational studies Diabetes Care 31 2008 1672 1678
101. Y.A. Hosokawa, and J.L. Leahy Parallel reduction of pancreas insulin content and insulin secretion in 48-h tolbutamide-infused normoglycemic rats Diabetes 46 1997 808 813
102. 2+ concentration J Biol Chem 273 1998 33501 33507
103. 2+ influx by glibenclamide induces apoptosis in RINm5F cells Biochem Biophys Res Commun 271 2000 422 428
104. K. Maedler, R.D. Carr, D. Bosco, R.A. Zuellig, T. Berney, and M.Y. Donath Sulfonylurea induced β-cell apoptosis in cultured human islets J Clin Endocrinol Metab 90 2005 501 506
105. S. Del Guerra, L. Marselli, and R. Lupi Effects of prolonged in vitro exposure to sulphonylureas on the function and survival of human islets J Diabetes Complications 19 2005 60 64
106. M.S. Remedi, and C.G. Nichols Chronic antidiabetic sulfonylureas in vivo: reversible effects on mouse pancreatic β-cells PLoS Med 5 2008 e206
107. H. Yki-Jrvinen Thiazolidinediones N Engl J Med 351 2004 1106 1118
108. L.A. Leiter β-Cell preservation: a potential role for thiazolidinediones to improve clinical care in Type 2 diabetes Diabet Med 22 2005 963 972
109. J. Rosenstock, J. Rood, A. Cobitz, N. Biswas, H. Chou, and A. Garber Initial treatment with rosiglitazone/metformin fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes Diabetes Obes Metab 8 2006 650 660
110. Avandia [prescribing information] 2008 GlaxoSmithKline Research Triangle Park, NC
111. Actos [prescribing information] 2009 Takeda Pharmaceuticals North America, Inc Deerfield, IL
112. Y.K. Loke, S. Singh, and C.D. Furberg Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis CMAJ 180 2009 32 39
113. I.J. Douglas, S.J. Evans, S. Pocock, and L. Smeeth The risk of fractures associated with thiazolidinediones: a self-controlled case-series study PLoS Med 6 2009 e1000154
114. C.R. Dormuth, G. Carney, B. Carleton, K. Bassett, and J.M. Wright Thiazolidinediones and fractures in men and women Arch Intern Med 169 2009 1395 1402
115. FDA significantly restricts access to the diabetes drug Avandia [press release] Silver Spring, MD: US Food and Drug Administration, September 23, 2010 http://www.fda.gov/newsevents/newsroom/pressannouncements/UCM226975.htm Accessed October 20, 2010
116. European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim [press release] London: European Medicines Agency, September 23, 2010 http://www.ema.europa.eu/ema/index.jsp?curl=pages/news-and-events/news/2010/09/ news-detail-001119.jsp&murl=menus/news-and-events/news-and-events. jsp&mid=WC0b01ac058004d5c1&jsenabled=true Accessed October 20, 2010
117. I. Lingvay, P.F. Kaloyanova, B. Adams-Huet, K. Salinas, and P. Raskin Insulin as initial therapy in type 2 diabetes: effective, safe, and well accepted J Investig Med 55 2007 62 68
118. C.A. Leslie, W. Satin-Rapaport, D. Matheson, R. Stone, and G. Enfield Psychological insulin resistance: a missed diagnosis? Diabetes Spectr 7 1994 52 57
119. M.A. Nauck Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications Am J Med 2010 xx: xxx-xxx [this issue]
120. D.J. Drucker, and M.A. Nauck The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes Lancet 368 2006 1696 1705
121. J.A. Lovshin, and D.J. Drucker Incretin-based therapies for type 2 diabetes mellitus Nat Rev Endocrinol 5 2009 262 269
122. J. Buteau, S. Foisy, E. Joly, and M. Prentki Glucagon-like peptide 1 induces pancreatic β-cell proliferation via transactivation of the epidermal growth factor receptor Diabetes 52 2003 124 132
123. J. Buteau, S. Foisy, C.J. Rhodes, L. Carpenter, T.J. Biden, and M. Prentki Protein kinase Cζ activation mediates glucagon-like peptide-1-induced pancreatic β-cell proliferation Diabetes 50 2001 2237 2243
124. C. Tourrel, D. Bailb, M.J. Meile, M. Kergoat, and B. Portha Glucagon-like peptide-1 and exendin-4 stimulate β-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age Diabetes 50 2001 1562 1570
125. H. Hui, A. Nourparvar, X. Zhao, and R. Perfetti Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway Endocrinology 144 2003 1444 1455
126. L. Li, W. El-Kholy, C.J. Rhodes, and P.L. Brubaker Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B Diabetologia 48 2005 1339 1349
127. T.J. Moretto, D.R. Milton, and T.D. Ridge Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study Clin Ther 30 2008 1448 1460
128. R.A. DeFronzo, R.E. Ratner, J. Han, D.D. Kim, M.S. Fineman, and A.D. Baron 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
129. J.B. Buse, R.R. Henry, J. Han, D.D. Kim, M.S. Fineman, and A.D. Baron 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
130. B. Zinman, B.J. Hoogwerf, and S. Durn Garca The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial Ann Intern Med 146 2007 477 485
131. D.J. Drucker, J.B. Buse, K. Taylor DURATION-1 Study Group 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
132. M. Nauck, A. Frid, K. Hermansen LEAD-2 Study Group Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (Liraglutide Effect and Action in Diabetes)-2 study Diabetes Care 32 2009 84 90
133. R.E. Pratley, M. Nauck, T. Bailey 1860-LIRA-DPP-4 Study Group Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial Lancet 375 2010 1447 1456
134. P. Aschner, M.S. Kipnes, J.K. Lunceford, M. Sanchez, C. Mickel, and D.E. Williams-Herman 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
135. M. Hanefeld, G.A. Herman, M. Wu, C. Mickel, M. Sanchez, P.P. Stein Sitagliptin Study 014 Investigators Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes Curr Med Res Opin 23 2007 1329 1339
136. I. Raz, Y. Chen, and M. Wu Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes Curr Med Res Opin 24 2008 537 550
137. B. Charbonnel, A. Karasik, J. Liu, M. Wu, and G. Meininger 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
138. M.A. Nauck, G. Meininger, D. Sheng, L. Terranella, P.P. Stein 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 9 2007 194 205
139. R. Scott, T. Loeys, M.J. Davies, S.S. Engel Sitagliptin Study 801 Group Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes Diabetes Obes Metab 10 2008 959 969
140. B.J. Goldstein, M.N. Feinglos, J.K. Lunceford, J. Johnson, and D.E. Williams-Herman 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
141. I. Raz, M. Hanefeld, L. Xu, C. Caria, D. Williams-Herman, and H. Khatami Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus Diabetologia 49 2006 2564 2571
142. M. Marre, J. Shaw, M. Brndle LEAD-1 Sulfonylurea Study Group 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 Sulfonylurea) Diabet Med 26 2009 268 278
143. B. Zinman, J. Gerich, J.B. Buse LEAD-4 Study Investigators Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD) Diabetes Care 32 2009 1224 1230
144. D. Russell-Jones, A. Vaag, O. Schmitz Liraglutide Effect and Action in Diabetes 5 (LEAD-5) Met+Sulfonylurea Study Group Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 Met+Sulfonylurea): a randomised controlled trial Diabetologia 52 2009 2046 2055
145. J.B. Buse, J. Rosenstock, G. Sesti LEAD-6 Study Group Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6) Lancet 374 2009 39 47
146. K. Hermansen, M. Kipnes, E. Luo, D. Fanurik, H. Khatami, and P. Stein 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
147. J. Rosenstock, R. Brazg, P.J. Andryuk, K. Lu, and P. Stein 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 28 2006 1556 1568
148. J.E. Foley, and S. Sreenan Efficacy and safety comparison between the DPP-4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug-nave patients with type 2 diabetes Horm Metab Res 41 2009 905 909
149. E. Bosi, R.P. Camisasca, C. Collober, E. Rochotte, and A.J. Garber 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
150. A.J. Garber, J.E. Foley, and M.A. Banerji Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea Diabetes Obes Metab 10 2008 1047 1056
151. J. Rosenstock, M.A. Baron, R.P. Camisasca, F. Cressier, A. Couturier, and S. Dejager 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
152. A.J. Garber, A. Schweizer, M.A. Baron, E. Rochotte, and S. Dejager 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 9 2007 166 174
153. R.A. DeFronzo, P.R. Fleck, C.A. Wilson, Q. Mekki Alogliptin Study 010 Group Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in
154. J. Rosenstock, C. Aguilar-Salinas, E. Klein, S. Nepal, J. List, R. Chen CV181-011 Study Investigators Effect of saxagliptin monotherapy in treatment-nave patients with type 2 diabetes Curr Med Res Opin 25 2009 2401 2411
155. M. Jadzinsky, A. Pftzner, E. Paz-Pacheco, Z. Xu, E. Allen, R. Chen CV181-039 Investigators Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial Diabetes Obes Metab 11 2009 611 622
156. R.A. DeFronzo, M.N. Hissa, A.J. Garber Saxagliptin 014 Study Group The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes on metformin alone Diabetes Care 32 2009 1649 1655
157. P. Hollander, J. Li, E. Allen, R. Chen CV181-013 Investigators Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone J Clin Endocrinol Metab 94 2009 4810 4819
158. S. Mudaliar, and R.R. Henry Incretin therapies: effects beyond glycemic control Am J Med 122 suppl 2009 S25 S36
159. M.A. Nauck, M.M. Heimesaat, and K. Behle 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 87 2002 1239 1246
160. K.B. Degn, B. Brock, and C.B. Juhl Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia Diabetes 53 2004 2397 2403
161. K.B. Degn, C.B. Juhl, and J. Sturis 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
162. B. Ahrn, M. Landin-Olsson, P.A. Jansson, M. Svensson, D. Holmes, and A. Schweizer Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes J Clin Endocrinol Metab 89 2004 2078 2084
163. M.A. Nauck, U. Niedereichholz, and R. Ettler Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans Am J Physiol 273 pt 1 1997 E981 E988
164. W.T. Phillips, J.G. Schwartz, and C.A. McMahan Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients J Nucl Med 33 1992 1496 1500
165. E. Bertin, N. Schneider, and N. Abdelli Gastric emptying is accelerated in obese type 2 diabetic patients without autonomic neuropathy Diabetes Metab 27 2001 357 364
166. C.B. Juhl, M. Hollingdal, and J. Sturis Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes Diabetes 51 2002 424 429
167. C.M. Edwards, S.A. Stanley, and R. Davis Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers Am J Physiol Endocrinol Metab 281 2001 E155 E161
168. A. Vella, G. Bock, and P.D. Giesler Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes Diabetes 56 2007 1475 1480
169. E. Ferrannini, V. Fonseca, and B. Zinman 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 11 2009 157 166
170. A.R. Chacra, G.H. Tan, A. Apanovitch, S. Ravichandran, J. List, R. Chen CV181-040 Investigators Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial Int J Clin Pract 63 2009 1395 1406
171. M.A. Nauck, G.C. Ellis, P.R. Fleck, C.A. Wilson, Q. Mekki Alogliptin Study 008 Group Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study Int J Clin Pract 63 2009 46 55
172. R.E. Pratley, J.E. Reusch, P.R. Fleck, C.A. Wilson, Q. Mekki Alogliptin Study 009 Group Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study Curr Med Res Opin 25 2009 2361 2371
173. D.M. Kendall, M.C. Riddle, and J. Rosenstock 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
174. M.A. Nauck, S. Duran, and D. Kim 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
175. J.B. Buse, G. Sesti, W.E. Schmidt Liraglutide Effect Action in Diabetes-6 Study Group Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 diabetes Diabetes Care 33 2010 1300 1303
176. Bergenstal R, Wysham C, Yan P, Macconell L, Malloy J, Porter L. DURATION-2: exenatide once weekly demonstrated superior glycemic control and weight reduction compared to sitagliptin or pioglitazone after 26 weeks of treatment. Presented at the American Diabetes Association 69th Scientific Sessions; June 5-9, 2009; New Orleans, Louisiana.
177. M.P. Gilbert, and R.E. Pratley Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus Am J Med 122 suppl 2009 S11 S24
178. G.C. Weir, S. Mojsov, G.K. Hendrick, and J.F. Habener Glucagon-like peptide I (7-37) actions on endocrine pancreas Diabetes 38 1989 338 342
179. A. Garber, R. Henry, R. Ratner 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 438 439
180. 1c over 1 year in drug-nave patients with type 2 diabetes Diabet Med 24 2007 955 961
181. F.X. Pi-Sunyer, A. Schweizer, D. Mills, and S. Dejager Efficacy and tolerability of vildagliptin monotherapy in drug-nave patients with type 2 diabetes Diabetes Res Clin Pract 76 2007 132 138 (Pubitemid 46240373)
182. V. Fonseca, A. Schweizer, D. Albrecht, M.A. Baron, I. Chang, and S. Dejager Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes Diabetologia 50 2007 1148 1155
183. R.E. Pratley, M.S. Kipnes, P.R. Fleck, C. Wilson, Q. Mekki Alogliptin Study 007 Group Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy Diabetes Obes Metab 11 2009 167 176
184. 1c without causing weight gain or increased hypoglycaemia Diabetes Obes Metab 11 2009 1145 1152
185. C.J. Girman, T.D. Kou, and B. Cai Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes Diabetes Obes Metab 12 2010 766 771
186. R.A. Noel, D.K. Braun, R.E. Patterson, and G.L. Bloomgren Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study Diabetes Care 32 2009 834 838
187. US Food and Drug Administration Information for Healthcare ProfessionalsAcute pancreatitis and sitagliptin (marketed as Januvia and Janumet) [09-25-2009] http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm183764.htm Accessed September 9, 2010
188. Byetta [package insert] 2009 Eli Lilly and Company Indianapolis, IN
189. US Food and Drug Administration FDA Briefing Materials: LiraglutideApril 2, 2009 http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4422b2-01-FDA.pdf Accessed August 24, 2010