DPP-4 inhibitors: focus on safety

Bibliography

• Drucker DJ. The biology of incretin hormones. Cell Metab 2006;3:153-65
   PubMed Web of Science ®Google Scholar
• Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-57
   PubMed Web of Science ®Google Scholar
• Gautier JF, Fetita S, Sobngwi E, et al. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab 2005;31(3 Pt 1):233-42
   PubMed Web of Science ®Google Scholar
• Yip RG, Wolfe MM. GIP biology and fat metabolism. Life Sci 2000;66:91-103
   PubMed Web of Science ®Google Scholar
• Trümper A, Trümper K, Hörsch D. Mechanisms of mitogenic and anti-apoptotic signaling by glucose-dependent insulinotropic polypeptide in beta(INS-1) cells. J Endocrinol 2002;174:233-46
   PubMed Web of Science ®Google Scholar
• Trümper A, Trümper K, Trusheim H, et al. Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. Mol Endocrinol 2001;15:1559-70
   PubMed Web of Science ®Google Scholar
• Ross SA, Brown JC, Dupré J. Hypersecretion of gastric inhibitory polypeptide following oral glucose in diabetes mellitus. Diabetes 1977;26:525-9
   PubMed Web of Science ®Google Scholar
• Calanna S Christensen M, Holst JJ, Laferriere B, et al. Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 Diabetes. Systematic review and meta-analysis of clinical studies. Diabetes Care 2013;36(10):3346-52
   PubMed Web of Science ®Google Scholar
• Christensen M, Vedtofte L, Holst JJ, et al. GIP: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes 2011;60:3103-9
   PubMed Web of Science ®Google Scholar
• Christensen M, Calanna S, Sparre-Ulrich AH, et al. Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. Diabetes 2014;63:1-7
   Google Scholar
• Nauck MA, Verdari I, Deacon CF, et al. Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down? Diabetologia 2011;54(1):10-18
   PubMed Web of Science ®Google Scholar
• Holst JJ, Christensen M, Lund A, et al. Regulation of glucagon secretion by incretins. Diabetes Obes Metab 2011;13(Suppl 1):89-94
   PubMed Web of Science ®Google Scholar
• Ahrén B, Foley JE, Ferrannini E, et al. Changes in prandial glucagon levels after a 2-year treatment with vildagliptin or glimepiride in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Diabetes Care 2010;33(4):730-2
   PubMed Web of Science ®Google Scholar
• 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(1):301-7
   PubMed Web of Science ®Google Scholar
• Little TJ, Pilichiewicz AN, Russo A, et al. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. Diabetes Care 2013;36:1396-405
   PubMedGoogle Scholar
• Ahrén B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res 2004;36:867-76
   PubMed Web of Science ®Google Scholar
• Dupre J. Glycaemic effects of incretins in type 1 diabetes mellitus: a concise review, with emphasis on studies in humans. Regul Pept 2005;128:149-57
   PubMed Web of Science ®Google Scholar
• Neumiller JJ, Campbell RK. Liraglutide: a once-daily incretin mimetic for the treatment of type 2 diabetes mellitus. Ann Pharmacother 2009;43:1433-44
   PubMed Web of Science ®Google Scholar
• Norris SL, Lee N, Thakurta S, Chan BK. Exenatide efficacy and safety: a systematic review. Diabet Med 2009;26(9):837-46
   PubMed Web of Science ®Google Scholar
• Trujillo JM, Nuffer W. Albiglutide: a new GLP-1 receptor agonist for the treatment of type 2 diabetes. Ann Pharmacother 2014;48(11):1494-501
   PubMed Web of Science ®Google Scholar
• Amblee A. Dulaglutide for the treatment of type 2 diabetes. Drugs Today (Barc) 2014;50(4):277-89
   PubMed Web of Science ®Google Scholar
• Lyseng-Williamson KA. Sitagliptin. Drugs 2007;67:587-97
   PubMed Web of Science ®Google Scholar
• Karasik A, Aschner P, Katzeff H, et al. Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 2008;24:489-96
   PubMed Web of Science ®Google Scholar
• Croxtall JD, Keam SJ. Vildagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs 2008;68:2387-409
   PubMed Web of Science ®Google Scholar
• Forst T, Bramlage P. Vildagliptin, a DPP-4 inhibitor for the twice-daily treatment of type 2 diabetes mellitus with or without metformin. Expert Opin Pharmacother 2014;15:1299-313
   PubMed Web of Science ®Google Scholar
• Borja-Hart NL, Whalen KL. Saxagliptin: a new dipeptidyl peptidase 4 inhibitor for type 2 diabetes. Ann Pharmacother 2010;44:1046-53
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet 2010;49(9):573-88
   PubMed Web of Science ®Google Scholar
• Deeks ED. Linagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs 2012;72(13):1793-824
   PubMed Web of Science ®Google Scholar
• Andukuri R, Drincic A, Rendell M. Alogliptin: a new addition to the class of DPP-4 inhibitors. Diabetes Metab Dis Obes 2009;2:117-26
   PubMedGoogle Scholar
• Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs 2011;71(11):1441-67
   PubMed Web of Science ®Google Scholar
• Herman GA, Stevens C, Van Dyck K, et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005;78(6):675-88
   PubMed Web of Science ®Google Scholar
• Thomas L, Eckhardt M, Langkopf E, et al. BI 1356- a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther 2008;325(1):175-82
   PubMed Web of Science ®Google Scholar
• Graefe-Mody U, Retlich S, Friedrich C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin Pharmacokinet 2012;51(7):411-27
   PubMed Web of Science ®Google Scholar
• He YL Clinical pharmacokinetics and pharmacodynamics of vildagliptin. Clin Pharmacokinet 2012;51(3):147-62
   PubMed Web of Science ®Google Scholar
• He YL, Serra D, Wang Y, et al. Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus. Clin Pharmacokinet 2007;46(7):577-88
   PubMed Web of Science ®Google Scholar
• He YL, 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes. Diabetes Res Clin Pract 2007;76:132-8
   PubMed Web of Science ®Google Scholar
• He YL, Kulmatycki K, Zhang Y, et al. Pharmacokinetics of vildagliptin in patients with varying degrees of renal impairment. Int J Clin Pharmacol Ther 2013;51(9):693-703
   PubMed Web of Science ®Google Scholar
• Golightly LK, Drayna CC, McDermott MT. Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet 2012;51(8):501-14
   PubMed Web of Science ®Google Scholar
• Graefe-Mody U, Giessmann T, Ring A, et al. A randomized, open-label, crossover study evaluating the effect of food on the relative bioavailability of linagliptin in healthy subjects. Clin Ther 2011;33(8):1096-103
   PubMed Web of Science ®Google Scholar
• He YL, Flannery B, Campestrini J, et al. Effect of food on the pharmacokinetics of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet in healthy volunteers. Curr Med Res Opin 2008;24(6):1703-9
   PubMed Web of Science ®Google Scholar
• Karim A, Covington P, Christopher R, et al. Pharmacokinetics of alogliptin when administered with food, metformin, or cimetidine: a two- phase, crossover study in healthy subjects. Int J Clin Pharmacol Ther 2010;48(1):46-58
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacokinetic and pharmacodynamic evaluation of sitagliptin plus metformin. Expert Opin Drug Metab Toxicol 2010;6(10):1265-76
   PubMed Web of Science ®Google Scholar
• Mistry GC, Bergman AJ, Zheng W, et al. Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects. Br J Clin Pharmacol 2008;66(1):36-42
   PubMed Web of Science ®Google Scholar
• Patel CG, Kornhauser D, Vachharajani N, et al. Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects. Diabetes Obes Metab 2011;13(7):604-14
   PubMed Web of Science ®Google Scholar
• Serra D, He YL, Bullock J, et al. Evaluation of pharmacokinetic and pharmacodynamic interaction between the dipeptidyl peptidase IV inhibitor vildagliptin, glyburide and pioglitazone in patients with type 2 diabetes. Int J Clin Pharmacol Ther 2008;46(7):349-64
   PubMed Web of Science ®Google Scholar
• Graefe-Mody U, Rose P, Ring A, et al. Assessment of the pharmacokinetic interaction between the novel DPP-4 inhibitor linagliptin and a sulfonylurea, glyburide, in healthy subjects. Drug Metab Pharmacokinet 2011;26(2):123-9
   PubMed Web of Science ®Google Scholar
• Graefe-Mody EU, Padula S, Ring A, et al. Evaluation of the potential for steady-state pharmacokinetic and pharmacodynamic interactions between the DPP-4 inhibitor linagliptin and metformin in healthy subjects. Curr Med Res Opin 2009;25(8):1963-72
   PubMed Web of Science ®Google Scholar
• Graefe-Mody EU, Jungnik A, Ring A, et al. Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase-4 inhibitor linagliptin and pioglitazone in healthy volunteers. Int J Clin Pharmacol Ther 2010;48(10):652-61
   PubMed Web of Science ®Google Scholar
• Gomis R, Espadero RM, Jones R, et al. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011;13(7):653-61
   PubMed Web of Science ®Google Scholar
• Fleck P, Karim A, Harris S, et al. Lack of effect of multiple doses of alogliptin benzoate (syr-322) on the pharmacokinetics of glyburide in healthy subjects [abstract]. Diabetes 2007;56(Suppl 1):541
   PubMedGoogle Scholar
• Munsaka M, Wann E, Fleck P, et al. Coadministration of pioglitazone or glyburide and alogliptin: pharmacokinetic drug interaction assessment in healthy participants. J Clin Pharmacol 2009;49(10):1210-19
   PubMed Web of Science ®Google Scholar
• Ayalasomayajula SP, Dole K, He YL, et al. Evaluation of the potential for steady-statepharmacokinetic interaction between vildagliptin and simvastatin in healthy subjects. Curr Med Res Opin 2007;23(12):2913-20
   PubMed Web of Science ®Google Scholar
• Cerra M, Luo WL, Li SX, et al. The effects of simvastatin on the pharmacokinectics of sitagliptin. J Popul Ther Clin Pharmacol 2012;19(3):e356-60
   PubMedGoogle Scholar
• Scheen AJ. Pharmacokinetic evaluation of atorvastatin and sitagliptin in combination for the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol 2012;8(6):745-58
   PubMed Web of Science ®Google Scholar
• Patel CG, Li L, Girgis S, et al. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole. Clin Pharmacol 2011;3:13-25
   PubMedGoogle Scholar
• Graefe-Mody U, Huettner S, Stähle H, et al. Effect of linagliptin (BI 1356) on the steady-state pharmacokinetics of simvastatin. Int J Clin Pharmacol Ther 2010;48(6):367-74
   PubMed Web of Science ®Google Scholar
• Karim A, Harris S, Fleck P, et al. Effect of fluconazole, ketoconazole, and gemfibrozil on the pharmacokinetics of alogliptin benzoate (SYR-322) in healthy subjects [abstract 105]. J Clin Pharmacol 2007;47(9):1207
   Web of Science ®Google Scholar
• Karim A, Fleck P, Harris S, et al. Lack of pharmacokinetic interaction between alogliptin, a highly selective dipeptidyl peptidase-4 inhibitor, and atorvastatin in healthy subjects [abstract]. Clin Pharmacol Ther 2008;83(Suppl 1):S14
   PubMed Web of Science ®Google Scholar
• Friedrich C, Port A, Ring A, et al. Effect of multiple oral doses of linagliptin on the steady-state pharmacokinetics of a combination oral contraceptive in healthy female adults: an open-label, two-period, fixed-sequence, multiple-dose study. Clin Drug Investig 2011;31(9):643-53
   PubMed Web of Science ®Google Scholar
• Friedrich C, Port A, Ring A, et al. Effect of multiple oral doses of linagliptin on the steady-state pharmacokinetics of a combination oral contraceptive in healthy female adults: an open-label, two-period, fixed-sequence, multiple-dose study. Clin Drug Investig 2011;31(9):643-53
   PubMed Web of Science ®Google Scholar
• Karim A, Copa A, Fleck P, et al. Effects of alogliptin on the pharmacokinetics and pharmacodynamics of norethindrone and ethinyl estradiol (ORTHO-NOVUM(R) 1/35) in healthy adult female subjects [abstract]. Clin Pharmacol Ther 2008;83(Suppl):S13
   Google Scholar
• Wright DH, Herman GA, Maes A, et al. Multiple doses of sitagliptin, a selective DPP-4 inhibitor, do not meaningfully alter pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 2009;49(10):1157-67
   PubMed Web of Science ®Google Scholar
• He YL, Sabo R, Riviere GJ, et al. Effect of the novel oral dipeptidyl peptidase IV inhibitor vildagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Curr Med Res Opin 2007;23(5):1131-8
   PubMed Web of Science ®Google Scholar
• Graefe-Mody EU, Brand T, Ring A, et al. Effect of linagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. Int J Clin Pharmacol Ther 2011;49(5):300-10
   PubMed Web of Science ®Google Scholar
• Karim A, Harris S, Fleck P, et al. Assessment of drug interaction between alogliptin benzoate (SYR-322), a highly selective dipeptidyl peptidase-4 inhibitor, and warfarin at steady state [abstract106]. J Clin Pharmacol 2007;47(9):1207
   Google Scholar
• He YL, Sabo R, Sunkara G, et al. Evaluation of pharmacokinetic interactions between vildagliptin and digoxin in healthy volunteers. J Clin Pharmacol 2007;47(8):998-1004
   PubMed Web of Science ®Google Scholar
• Friedrich C, Ring A, Brand T, et al. Evaluation of the pharmacokinetic interaction after multiple oral doses of linagliptin and digoxin in healthy volunteers. Eur J Drug Metab Pharmacokinet 2011;36(1):17-24
   PubMed Web of Science ®Google Scholar
• Karim A, Fleck P, Harris S, et al. Lack of pharmacokinetic interaction between multiple doses of the dipeptidyl peptidase-4 inhibitor alogliptin and digoxin in healthy subjects [abstract]. Clin Pharmacol Ther 2008;83(Suppl 1):S12-13
   Google Scholar
• Brown NJ, Byiers S, Carr D, et al. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension 2009;54(3):516-23
   PubMed Web of Science ®Google Scholar
• He YL, Ligueros-Saylan M, Sunkara G, et al. Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects. J Clin Pharmacol 2008;48(1):85-95
   PubMed Web of Science ®Google Scholar
• Maes MB, Dubois V, Brandt I, et al. Dipeptidyl peptidase 8/9-like activity in human leukocytes. J Leukoc Biol 2007;81(5):1252-7
   PubMed Web of Science ®Google Scholar
• Reinhold D, Goihl A, Wrenger S, et al. Role of dipeptidyl peptidase IV (DPP IV)-like enzymes in T lymphocyte activation: investigations in DPP IV/CD26-knockout mice. Clin Chem Lab Med 2009;2009:47(3):268-74
   Google Scholar
• Burkey BF, Hoffmann PK, Hassiepen U, et al. Adverse effects of dipeptidyl peptidases 8 and 9 inhibition in rodents revisited. Diabetes Obes Metab 2008;10(11):1057-61
   PubMed Web of Science ®Google Scholar
• Shah Z, Kampfrath T, Deiuliis JA, et al. Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation 2011;124(21):2338-49
   PubMed Web of Science ®Google Scholar
• Anz D, Kruger S, Haubner S, et al. The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptiveimmune responses. Diabetes Obes Metab 2014;16(6):569-72
   PubMed Web of Science ®Google Scholar
• Schürmann C, Linke A, Engelmann-Pilger K, et al. The dipeptidyl peptidase-4 inhibitor linagliptin attenuates inflammation and accelerates epithelialization in wounds of diabetic ob/ob mice. J Pharmacol Exp Ther 2012;342(1):71-80
   PubMed Web of Science ®Google Scholar
• 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;174(1):120-8
   PubMed Web of Science ®Google Scholar
• Willemen MJ, Mantel-Teeuwisse AK, Straus SM, et al. Use of dipeptidyl peptidase-4 inhibitors and the reporting of infections: a disproportionality analysis in the World Health Organization VigiBase. Diabetes Care 2011;34(2):369-74
   PubMed Web of Science ®Google Scholar
• Satoh-Asahara N, Sasaki Y, Wada H, et al. Dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients. Metabolism 2013;62(3):347-51
   PubMed Web of Science ®Google Scholar
• Ogawa T, Linz W, Stevenson M, et al. Evidence for load-dependent and load-independent determinants of cardiac natriuretic peptide production. Circulation 1996;93:2059-67
   PubMed Web of Science ®Google Scholar
• Boerrigter G, Costello-Boerrigter LC, et al. Des-serine–proline brain natriuretic peptide 3–32 in cardiorenal regulation. Am J Physiol Regul Integr Comp Physiol 2007;292:R897-901
   PubMed Web of Science ®Google Scholar
• Moilanen AM, Rysa J, Mustonen E, et al. Intramyocardial BNP gene delivery improves cardiac function through distinct context dependent mechanisms. Circ Heart Fail 2011;4:483-95
   PubMed Web of Science ®Google Scholar
• Palazzuoli A, Antonelli G, Quatrini I, Nuti R. Natriuretic peptides in heart failure: where we are, where we are going. Intern Emerg Med 2011;6:63-8
   PubMed Web of Science ®Google Scholar
• Brandt I, Lambeir AM, Ketelslegers JM, et al. Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-serpro form. Clin Chem 2006;52:82-7
   PubMed Web of Science ®Google Scholar
• Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964-7
   PubMed Web of Science ®Google Scholar
• Gomez N, Touihri K, Matheeussen V, et al. Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing induced heart failure. Europ J Heart Fail 2012;14:14-21
   PubMed Web of Science ®Google Scholar
• Zaruba MM, Theiss HD, Vallaster M, et al. 2009 Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell 2009;4:313-23
   PubMed Web of Science ®Google Scholar
• Huisamen B, Genis A, Marais E, Lochner A. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats. Cardiovasc Drugs and Therapy 2011;25:13-20
   PubMed Web of Science ®Google Scholar
• Hocher B, Sharkovska Y, Mark M, et al. The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats. Int J Cardiol 2013;167:87-93
   PubMed Web of Science ®Google Scholar
• 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-1a. Diabetes Care 2010;33:1607-9
   PubMed Web of Science ®Google Scholar
• Mistry GC, Maes AL, Lasseter KC, et al. Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension. J Clin Pharm 2008;48:592-8
   PubMed Web of Science ®Google Scholar
• Bergenstal RM, Wysham C, Macconell L, et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 2010;376:431-9
   PubMed Web of Science ®Google Scholar
• Russell-Jones D, Cuddihy RM, Hanefeld M, et al. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care 2012;35:252-8
   PubMed Web of Science ®Google Scholar
• Read PA, Khan FZ, Heck PM, et al. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging 2010;3:195-201
   PubMed Web of Science ®Google Scholar
• Mita T, Katakami N, Shiraiwa T, et al. Rationale, design, and baseline characteristics of a clinical trial for prevention of atherosclerosis in patients with insulin-treated type 2 diabetes mellitus using DPP-4 inhibitor: the Sitagliptin Preventive study of Intima-media thickness Evaluation (SPIKE). Diabetol Metab Syndr 2014;6(1):35
   PubMedGoogle Scholar
• McMurray J, Ponikowski P, Bolli G, et al. The vildagliptin in ventricular dysfunction diabetes trial (VIVIDD). Presented at the European Heart Failure Meeting; 25-28 May 2013; Lisbon
   Google Scholar
• Scheller NM, Mogensen UM, Andersson C, et al. All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population. Diabetes Obes Metab 2014;16(3):231-6
   PubMed Web of Science ®Google Scholar
• Engel S, 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
   PubMed Web of Science ®Google Scholar
• 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(6):485-94
   PubMed Web of Science ®Google Scholar
• Iqbal N, Parker A, Frederich R, et al. Assessment fof the cardiovascular safety of of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials. Cardiovasc Diabetol 2014;13:33
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369(14):1327-35
   PubMed Web of Science ®Google Scholar
• Zannad F, Cannon C, Cushman W, et al. Alogliptin in patients with type 2 diabetes after acute coronary syndromes: heart failure outcomes and cardiovascular safety in heart failure patients. J Am Coll Cardiol 2014;63:12_S
   PubMedGoogle Scholar
• Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369(14):1317-26
   PubMed Web of Science ®Google Scholar
• Weir DL, McAlister FA, Senthiselvan A, et al. Sitagliptin use in patients with diabetes and heart failure: a population based retrospective cohort study. JCHF 2014;2:573-82
   Google Scholar
• Wu S, Hopper I, Skiba M, Krum H. Dipeptidylpeptidase-4 inhibitors and cardiovascular outcomes: Meta-analysis of randomized clinical trials with 55,141 participants. Cardiovasc Ther 2014;32(4):147-58
   PubMed Web of Science ®Google Scholar
• Emea.europa.edu [homepage on the internet]. Summary of product characteristics of vildagliptin 2007. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf. [Last accessed 5 Dec 2014]
   Google Scholar
• Rosenstock J, Marx N, Kahn S, et al. Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial. Diab Vasc Dis Res 2013;10:289-301
   PubMed Web of Science ®Google Scholar
• CARMELINA: a multicenter, international, randomized, parallel group, double-blind, placebo-controlled, cardiovascular safety and renal microvascular outcome study with linagliptin, 5 mg once daily in patients with type 2 diabetes mellitus at high vascular risk NCT01897532
   Google Scholar
• Green JB, Bethel MA, Paul SK, et al. Rationale, design, and organization of a randomized, controlled trial evaluating cardiovascular outcomes with sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. Am Heart J 2013;166(6):983-9
   PubMed Web of Science ®Google Scholar
• Lee YS, Jun HS. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism 2014;63(1):9-19
   PubMed Web of Science ®Google Scholar
• Rondas D, D’Hertog W, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of beta-cell dysfunction and death. Diabetes Obes Metab 2013;15(Suppl 3):185-92
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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(7):2595-604
   PubMed Web of Science ®Google Scholar
• 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(7):2118-25
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and pancreatitis risk: a meta-analysis of randomized clinical trials. Diabetes Metab Res Rev 2013;29(8):624-30
   PubMedGoogle Scholar
• Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs — FDA and EMA assessment. N Engl J Med 2014;370:794-7
   PubMed Web of Science ®Google Scholar
• Saxagliptin (BMS-477118) FDA’s endocrinologic and metabolic drugs. Advisory committee briefing document for April 2009 Meeting NDA 22-350; 2 March 2009; Silver Spring, Maryland
   Google Scholar
• Emea.europa.edu [homepage on the internet]. Scientific discussion on vlidagliptin: pharmacodynamics, pharmacokinetics, efficacy and safety 2007. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000771/WC500020330.pdf. [Last accessed 5 Dec 2014]
   Google Scholar
• Merck shares Januvia safety data following FDA decision to delay approval of rival drug. Internal medicine World Report. 2006. Available from: http://www.hcplive.com/publications/internal-medicine-world-report/2006/2006-12. [Last accessed 5 Dec 2014]
   Google Scholar
• Fda.gov/medwatch[homepage on the internet]. Patient information Januvia. 2007. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm196611.htm. [Last accessed 5 Dec 2014]
   Google Scholar
• Rendell M, Drincic A, Andukuri R. Alogliptin benzoate for the treatment of type 2 diabetes. Expert Opin Pharmacother 2012;13(4):553-63
   PubMed Web of Science ®Google Scholar
• Miyazaki M, Kato M, Tanaka K, et al. Increased hepatic expression of dipeptidyl peptidase-4 in non-alcoholic fatty liver disease and its association with insulin resistance and glucose metabolism. Mol Med Rep 2012;5:729-33
   PubMed Web of Science ®Google Scholar
• Balaban YH, Korkusuz P, Simsek H, et al. Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol 2007;6:242-50
   PubMed Web of Science ®Google Scholar
• He YL, Sabo R, Campestrini J, et al. The influence of hepatic impairment on the pharmacokinetics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin. Eur J Clin Pharmacol 2007;63(7):677-86
   PubMed Web of Science ®Google Scholar
• Merck Sharp & Dohme Corp. Januvia PI 2010. http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf [Accessed May 2010]
   Google Scholar
• Bristol-Myers Squibb. Onglyza PI. http://packageinserts.bms.com/pi/pi_onglyza.pdf [Accessed Dec 2014]
   Google Scholar
• Takeda, Inc. Nesina package insert 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022271s000lbl.pdf [Accessed June 2014]
   Google Scholar
• Galvus product information 2013. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf [Accessed June 2014]
   Google Scholar
• Boehringer Ingelheim Pharmaceuticals, Inc. Trajenta SPC 2014. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002110/WC500115745.pdf [Accessed May 2013]
   Google Scholar
• ACCORD Study Group. Gerstein HC, Miller ME, Genuth S, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364(9):818-28
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009;180(8):821-7
   PubMed Web of Science ®Google Scholar
• Farngren J, Persson M, Schweizer A, et al. Vildagliptin reduces glucagon during hyperglycemia and sustains glucagon counterregulation during hypoglycemia in type 1 diabetes. Clin Endocrinol Metab 2012;97(10):3799-806
   Google Scholar
• Farngren J, Persson M, Schweizer A, et al. Glucagon dynamics during hypoglycaemia and food-re-challenge following treatment with vildagliptin in insulin-treated patients with type 2 diabetes. Diabetes Obes Metab 2014;16(9):812-18
   PubMed Web of Science ®Google Scholar
• 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(2):157-66
   PubMed Web of Science ®Google Scholar
• Arechavaleta R, Seck T, Chen Y, et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2011;13(2):160-8
   PubMed Web of Science ®Google Scholar
• Göke B, Gallwitz B, Eriksson J, D1680C00001 Investigators. Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. Int J Clin Pract 2010;64(12):1619-31
   PubMed Web of Science ®Google Scholar
• 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(9840):475-83
   PubMed Web of Science ®Google Scholar
• Pratley RE, Kipnes MS, Fleck PR. 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 2009;11(2):167-76
   PubMed Web of Science ®Google Scholar