Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: Comparison, efficacy and safety

Expert Opinion on Pharmacotherapy

Volumn 14, Issue 15, 2013, Pages 2047-2058

  Deacon, Carolyn F ^a   Holst, Jens J ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Alogliptin; Dipeptidyl peptidase 4; Glucagon like peptide 1; Incretin; Linagliptin; Saxagliptin; Sitagliptin; Type 2 diabetes; Vildagliptin

Indexed keywords

ALOGLIPTIN; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; HEMOGLOBIN A1C; INCRETIN; LINAGLIPTIN; METFORMIN; SAXAGLIPTIN; SITAGLIPTIN; VILDAGLIPTIN;

ADD ON THERAPY; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED CANCER; DRUG METABOLISM; DRUG SAFETY; ENZYME INHIBITION; GLOMERULUS FILTRATION; GLOMERULUS FILTRATION RATE; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS CANCER; PANCREATITIS; REVIEW; SIDE EFFECT; WEIGHT GAIN;

ANIMALS; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HUMANS; TREATMENT OUTCOME;

EID: 84884538670     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2013.824966     Document Type: Review

References (111)

1. Holst JJ. The physiology of glucagon-like peptide. Physiol Rev 2007;87:1409-39
2. Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967;46:1954-62
3. Holst JJ, Deacon CF, Vilsbøll T, et al. Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol Med 2008;14:161-8
4. Deacon CF, Holst JJ. Pharmacology of GLP-1-based therapies. Rev Endocrinol 2008;17-22
5. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986;29:46-52
6. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301-7
7. Vilsbøll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia 2002;45:1111-19
8. Nauck MA, Kleine N, Orskov C, et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulindependent) diabetic patients. Diabetologia 1993;36:741-4
9. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-30
10. Nauck MA, Wollschlager D, Werner J, et al. Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia 1996;39:1546-53
11. Deacon CF, Nauck MA, Toft-Nielsen M, et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126-31
12. Deacon CF, Hughes TE, Holst JJ. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes 1998;47:764-9
13. Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 2011;13:7-18
14. Ahren B, Schweizer A, Dejager S, et al. Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans. Diabetes Obes Metab 2011;13:775-83
15. Aroda VR, Henry RR, Han J, et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther 2012;34:1247-58
16. Park H, Park C, Kim Y, Rascati KL. Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta-analysis. Ann Pharmacother 2012;46:1453-69
17. Scheen AJ, Charpentier G, Ostgren CJ, et al. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2010;26:540-9
18. Asti A, D'Alessandro A, D'Alessandro G, et al. Sitagliptin vs saxagliptin in decompensated type 2 diabetes mellitus patients [abstract]. Diabetologia 2012;55(Suppl 1):S343
19. Marfella R, Barbieri M, Grella R, et al. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-h acute glucose fluctuations. J Diabetes Complications 2010;24:79-83
20. Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care 2012;35:2076-82
21. Guerci B, Monnier L, Serusclat P, et al. Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized Optima study. Diabetes Metab 2012;38:359-66
22. Avogaro A. Comments on the article Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-h acute glucose fluctuations by Marfella et al.: (Journal of Diabetes and Its Complications 24 [2010] 79-83). J Diabetes Complications 2011;25:352-3
23. Marfella R, Paolisso G. Reply to the Comments on the article 'Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-h acute glucose fluctuations', by Avogaro (Journal of Diabetes and Its Complications 25 [2011] 352-353). J Diabetes Complications 2011;25:405-6
24. Siegelaar SE, Kerr L, Jacober SJ, Devries JH. A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study. Diabetes Care 2011;34:855-7
25. Kilpatrick ES, Rigby AS, Atkin SL. Effect of glucose variability on the long-term risk of microvascular complications in type 1 diabetes. Diabetes Care 2009;32:1901-3
26. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012;55:1577-96
27. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009;15:540-59
28. Migoya EM, Bergeron R, Miller JL, et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin Pharmacol Ther 2010;88:801-8
29. Pratley RE, McCall T, Fleck PR, et al. Alogliptin use in elderly people: a pooled analysis from phase 2 and 3 studies. J Am Geriatr Soc 2009;57:2011-19
30. Barzilai N, Guo H, Mahoney EM, et al. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin 2011;27:1049-58
31. Schweizer A, Dejager S, Foley JE, et al. 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
32. Furukawa S, Kumagi T, Miyake T, et al. Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: a case report and a review of the literature. Endocr J 2012;59:329-33
33. Kim YG, Hahn S, Oh TJ, et al. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 2013;56:696-708
34. Karagiannis T, Paschos P, Paletas K, et al. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ 2012;344:e1369
35. Seck T, Nauck M, Sheng D, et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study. Int J Clin Pract 2010;64(5):562-76
36. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012;380:475-83
37. 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;27:318-26
38. Deacon CF, Mannucci E, Ahren B. Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2 diabetes-a review and meta analysis. Diabetes Obes Metab 2012;14:762-7
39. Nowicki M, Rychlik I, Haller H, et al. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab 2011;13:523-32
40. Kothny W, Shao Q, Groop PH, Lukashevich V. One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab 2012;14:1032-9
41. Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency. Diabetes Care 2013;36:1067-73
42. McGill JB, Sloan L, Newman J, et al. Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind, placebo-controlled study. Diabetes Care 2013;36:237-44
43. Yki-Jarvinen H, Rosenstock J, Duran-Garcia S, et al. Long-term safety and efficacy of linagliptin as add-on therapy to basal insulin in patients with type 2 diabetes: a 52-week randomised, placebo-controlled trial [abstract]. Diabetologia 2012;55(Suppl 1):S9. Available from: http://www.easdvirtualmeeting. org/resources/2894 [Accessed 12 June 2013]
44. Arjona Ferreira JC, Corry D, Mogensen CE, et al. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis 2013;61:579-87
45. Ito M, Abe M, Okada K, et al. The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis. Endocr J 2011;58:979-897
46. Lane JT, Odegaard DE, Haire CE, et al. Sitagliptin therapy in kidney transplant recipients with new-onset diabetes after transplantation. Transplantation 2011;92:e56-7
47. Werzowa J, Hecking M, Haidinger M, et al. Vildagliptin and pioglitazone in patients with impaired glucose tolerance after kidney transplantation: a randomized, placebo-controlled clinical trial. Transplantation 2013;95:456-62
48. Ligueros-Saylan M, Foley JE, Schweizer A, et al. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes Metab 2010;12:495-509
49. Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin 2011;27(Suppl 3):57-64
50. 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
51. Goo-en K, Graber S. Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2012;14:1061-72
52. Cai L, Cai Y, Lu ZJ, et al. The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. J Clin Pharm Ther 2012;37:386-98
53. Engel SS, Round E, Golm GT, et al. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diab Ther 2013;4:119-45
54. Price JD, Linder G, Li WP, et al. Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study. Clin Exp Immunol 2013; [Epub ahead of print]
55. Goodwin SR, Reeds DN, Royal M, et al. Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study. J Clin Endocrinol Metab 2013;98:743-51
56. Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med 2008;358:1970-1
57. Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care 2009;32:834-8
58. Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care 2010;33:2349-254
59. Girman CJ, Kou TD, Cai B, et al. Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes. Diabetes Obes Metab 2010;12:766-71
60. Yang L, He Z, Tang X, Liu J. Type 2 diabetes mellitus and the risk of acute pancreatitis: a meta-analysis. Eur J Gastroenterol Hepatol 2013;25:225-31
61. Brodovicz KG, Kou TD, Alexander CM, et al. Impact of diabetes duration and chronic pancreatitis on the association between type 2 diabetes and pancreatic cancer risk. Diabetes Obes Metab 2012;14:1123-8
62. Matveyenko AV, Dry S, Cox HI, et al. Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes 2009;58:1604-15
63. Gier B, Matveyenko AV, Kirakossian D, et al. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras (G12D) mouse model. Diabetes 2012;61:1250-62
64. Nachnani JS, Bulchandani DG, Nookala A, et al. Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas. Diabetologia 2010;53:153-9
65. Aston-Mourney K, Subramanian SL, Zraika S, et al. One year of sitagliptin treatment protects against islet amyloid-associated beta-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice. Am J Physiol Endocrinol Metab 2013; [Epub ahead of print]
66. Koehler JA, Baggio LL, Lamont BJ, et al. Glucagon-like peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice. Diabetes 2009;582148-2161
67. Tatarkiewicz K, Smith PA, Sablan EJ, et al. Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents. Am J Physiol Endocrinol Metab 2010;299:E1076-86
68. Engel SS, Williams-Herman DE, Golm GT, et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract 2010;64:984-90
69. Busch SJ, Hoffmann P, Sahota P, et al. Studies in rodents with the dipeptidyl peptidase-4 inhibitor vildagliptin to evaluate possible drug-induced pancreatic histological changes that are predictive of pancreatitis and cancer development in man. Diabetes Obes Metab 2013;15:72-6
70. Nyborg NC, Mølck AM, Madsen LW, Knudsen LB. The human GLP-1 analog liraglutide and the pancreas: evidence for the absence of structural pancreatic changes in three species. Diabetes 2012;61:1243-9
71. Lando HM, Alattar M, Dua AP. Elevated amylase and lipase levels in patients using glucagonlike peptide-1 receptor agonists or dipeptidyl-peptidase- 4 inhibitors in the outpatient setting. Endocr Pract 2012;18:472-27
72. Garg R, Hussey C, Ibrahim S. Pancreatitis associated with the use of sitagliptin and orlistat combination: a case report. Diabet Med 2010;27:485-6
73. Girgis CM, Champion BL. Vildagliptin-induced acute pancreatitis. Endocr Pract 2011;17:e48-50
74. Singh S, Chang HY, Richards TM, et al. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013;173:534-9
75. Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141:150-6 . Controversial, analysis suggesting incretin therapies may be associated with increased risk of pancreatitis and malignancies.
76. Drucker DJ, Sherman SI, Bergenstal RM, Buse JB. The safety of incretin-based therapies-review of the scientific evidence. J Clin Endocrinol Metab 2011;96:2027-31
77. Raschi E, Piccinni C, Poluzzi E, et al. The association of pancreatitis with antidiabetic drug use: gaining insight through the FDA pharmacovigilance database. Acta Diabetol 2011; [Epub ahead of print]
78. Scheen A. Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis. Expert Opin Drug Saf 2013;12:545-57
79. Butler AE, Campbell-Thompson M, Gurlo T, et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 2013;62:2595-604
80. Kahn SE. Incretin therapy and islet pathology-a time for caution. Diabetes 2013;62:2178-80
81. Schweizer A, Dejager S, Foley JE, Kothny W. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies. Vasc Health Risk Manag 2011;7:49-57
82. Schernthaner G, Barnett AH, Emser A, et al. Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus. Diabetes Obes Metab 2012;14:470-8
83. Gokhale M, Sturmer T, Gray C, et al. Dipeptidyl peptidase 4 inhibitors and comparative pancreatic cancer risk. Late-breaking abstract presented at 73rd Scientific Sessions of the American Diabetes association; 21-25 June 2013; Chicago. Available from: http://www. abstractsonline.com/Plan/ViewAbstract. aspx?sKey=0687e7c8-c97d-442b-92ecae505e051854&cKey=8aeb2da8-eb73-4212-8ff0- 86b510c085b4&mKey= {89918D6D-3018-4EA9-9D4F-711F98A7AE5D} [Accessed 4 July 2013]
84. Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin 2009;25:1019-27
85. Richard KR, Shelburne JS, Kirk JK. Tolerability of dipeptidyl peptidase-4 inhibitors: a review. Clin Ther 2011;33:1609-29
86. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427-43
87. Nathan DM, Buse JB, Kahn SE, et al. Rationale and design of the glycemia reduction approaches in diabetes a comparative effectiveness study (GRADE). Diabetes Care 2013; [Epub ahead of print]
88. Hocher B, Reichetzeder C, Alter ML. Renal and cardiac effects of DPP4 inhibitors-from preclinical development to clinical research. Kidney Blood Press Res 2012;36(1):65-84
89. Mega C, de Lemos ET, Vala H, et al. Diabetic nephropathy amelioration by a low-dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat). Exp Diabetes Res 2011;2011:162092
90. Sharkovska Y, Alter M, Reichetzeder C, et al. Renoprotective effect of the DPP-4 inhibitor linagliptin in db/db mice [abstract]. Diabetes 2012;61(Suppl 1):A251
91. Hattori S. Sitagliptin reduces albuminuria in patients with type 2 diabetes. Endocr J 2011;58(1):69-73
92. Groop PH, Cooper M, Perkovic V, et al. Effects of the DPP-4 inhibitor linagliptin on albuminuria in patients with type 2 diabetes and diabetic nephropathy [abstract]. Diabetologia 2012; 44(Suppl 1):S20. Available from: http://www.easdvirtualmeeting.org/resources/2530 [Accessed 12 June 2013]
93. Cai B, Katz L, Alexander CM, et al. Characteristics of patients prescribed sitagliptin and other oral antihyperglycaemic agents in a large US claims database. Int J Clin Pract 2010;64:1601-8
94. Nauck MA. A critical analysis of the clinical use of incretin-based therapies: the benefits by far outweigh the potential risks. Diabetes Care 2013;36:2126-32
95. Cohen D. Has pancreatic damage from glucagon suppressing diabetes drugs been underplayed? BMJ 2013;346:f3680
96. Butler PC, Elashoff M, Elashoff R, Gale EA. A critical analysis of the clinical use of incretin-based therapies: are the GLP-1 therapies safe? Diabetes Care 2013;36:2118-25
97. Drucker DJ. Incretin action in the pancreas: potential promise, possible perils, and pathological pitfalls. Diabetes 2013; [Epub ahead of print]
98. NIDDK-NCI Workshop on Pancreatitis-Diabetes-Pancreatic Cancer. Available from: www2.niddk.nih.gov/News/Calendar/PDPC2013 [Accessed 10 July 2013]
99. ADA/EASD/IDF recommendations for clinicians and people with diabetes concerning the use of incretin therapy and pancreatic disease. Available from: http://easd.org/index.php? option=com-content&view=article&id=172 [Accessed 4 July 2013]
100. Deacon CF, Marx N. Potential cardiovascular effects of incretin-based therapies. Expert Rev Cardiovasc Ther 2012;10:337-51
101. Patil HR, Al Badarin FJ, Al Shami HA, et al. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol 2012;110:826-33
102. Monami M, Ahren B, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013;15:112-20
103. Schweizer A, Dejager S, Foley JE, et al. Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large phase III type 2 diabetes population. Diabetes Obes Metab 2010;12:485-94
104. Frederich R, Alexander JH, Fiedorek FT, et al. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 2010;122:16-27
105. Johansen OE, Neubacher D, von Eynatten M, et al. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol 2012;11:3
106. Engel SS, Golm GT, Shapiro D, et al. Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis. Cardiovasc Diabetol 2013;12:3
107. White WB, Pratley R, Fleck P, et al. Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus. Diabetes Obes Metab 2013;15:668-73
108. Zaruba MM, Theiss HD, Vallaster M, et al. Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell 2009;4:313-23
109. Theiss HD, Gross L, Vallaster M, et al. Antidiabetic gliptins in combination with G-CSF enhances myocardial function and survival after acute myocardial infarction. Int J Cardiol 2013; [Epub ahead of print]
110. Fadini GP, Boscaro E, Albiero M, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care 2010;33:1607-9
111. Theiss HD, Brenner C, Engelmann MG, et al. Safety and efficacy of SITAgliptin plus GRanulocyte-colony-stimulating factor in patients suffering from acute myocardial infarction (SITAGRAMI-Trial)-rationale, design and first interim analysis. Int J Cardiol 2010;145:282-3