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Sitagliptin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus

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Abstract

Sitagliptin (Januvia®, Xelevia™, Glactiv®, Tesavel®) is an orally administered, potent and highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) and was the first agent of its class to be approved for use in the management of adults with type 2 diabetes. Numerous randomized placebo- or active comparator-controlled trials have demonstrated the efficacy of sitagliptin in terms of improving glycaemic control in patients with type 2 diabetes, including its use as monotherapy, initial combination therapy (usually with fixed-dose combinations of sitagliptin/metformin), or add-on therapy to metformin or to other antihyperglycaemic drugs, with or without metformin. The primary endpoint of the clinical trials was the reduction from baseline in glycosylated haemoglobin (HbA1c), although sitagliptin also showed beneficial effects for other endpoints, such as the proportion of patients who achieved target HbA1c, and reductions from baseline in fasting plasma glucose (FPG) levels and 2-h postprandial glucose (PPG) levels. Sitagliptin was generally well tolerated in clinical trials, had a low risk of hypoglycaemia (although this depends on background therapy) and had a neutral effect on body weight. Despite concerns regarding a possible increased risk of rare pancreatic adverse events (e.g. pancreatitis) with glucagon-like peptide-1 (GLP-1)-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, no causal association has been found; regulators in Europe recently conducted a review of available data, concluding that there is little evidence that these drugs could cause pancreatic inflammation or pancreatic cancer. A similar review is planned in the USA and postmarketing surveillance will continue. Thus, oral sitagliptin is an effective and generally well tolerated treatment option for the management of patients with type 2 diabetes.

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References

  1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia 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). Diabetes Care. 2012;35(6):1364–79.

    CAS  PubMed  Google Scholar 

  2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35 Suppl 1:S64–71.

    Google Scholar 

  3. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2012;35 Suppl 1:S11–63.

    Google Scholar 

  4. International Diabetes Federation. Global diabetes plan 2011–2021. http://www.idf.org/sites/default/files/Global_Diabetes_Plan_Final.pdf. Accessed 11 Jul 2013.

  5. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.

    CAS  PubMed  Google Scholar 

  6. Roglic G, Unwin N. Mortality attributable to diabetes: estimates for the year 2010. Diabetes Res Clin Pract. 2010;87(1):15–9.

    PubMed  Google Scholar 

  7. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405–12.

    CAS  PubMed  Google Scholar 

  8. Moss SE, Klein R, Klein BE, et al. The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med. 1994;154(21):2473–9.

    CAS  PubMed  Google Scholar 

  9. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281(21):2005–12.

    CAS  PubMed  Google Scholar 

  10. Inzucchi SE, McGuire DK. New drugs for the treatment of diabetes: part II. Incretin-based therapy and beyond. Circulation. 2008;117(4):574–84.

    PubMed  Google Scholar 

  11. Ahren B. Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care. 2007;30(6):1344–50.

    CAS  PubMed  Google Scholar 

  12. Campbell RK. Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for the treatment of type 2 diabetes mellitus. Ann Pharmacother. 2007;41(1):51–60.

    CAS  PubMed  Google Scholar 

  13. Rosenstock J, Zinman B. Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. 2007;14(2):98–107.

    CAS  PubMed  Google Scholar 

  14. Dhillon S. Sitagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2010;70(4):489–512.

    CAS  PubMed  Google Scholar 

  15. Sitagliptin (Januvia) US prescribing information. 2013. http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf. Accessed 9 Jul 2013.

  16. Sitagliptin summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000722/WC500039054.pdf. Accessed 9 Jul 2013.

  17. Kim D, Wang L, Beconi M, et al. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1, 2, 4]triazolo[4,3-a]pyrazin-7(8H)- yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005;48(1):141–51.

    CAS  PubMed  Google Scholar 

  18. Bergman AJ, Stevens C, Zhou Y, et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther. 2006;28(1):55–72.

    CAS  PubMed  Google Scholar 

  19. Herman GA, Bergman A, Liu F, et al. Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol. 2006;46(8):876–86.

    CAS  PubMed  Google Scholar 

  20. Herman GA, Bergman A, Stevens C, et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab. 2006;91(11):4612–9.

    CAS  PubMed  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

  22. Lyseng-Williamson KA. Sitagliptin. Drugs. 2007;67(4):587–97.

    CAS  PubMed  Google Scholar 

  23. Golightly LK, Drayna CC, McDermott MT. Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012;51(8):501–14.

    CAS  PubMed  Google Scholar 

  24. Bergman A, Mistry GC, Luo WL, et al. Dose-proportionality of a final market image sitagliptin formulation, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers. Biopharm Drug Dispos. 2007;28(6):307–13.

    CAS  PubMed  Google Scholar 

  25. Bergman A, Ebel D, Liu F, et al. Absolute bioavailability of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers. Biopharm Drug Dispos. 2007;28(6):315–22.

    CAS  PubMed  Google Scholar 

  26. Vincent SH, Reed JR, Bergman AJ, et al. Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin in humans. Drug Metab Dispos. 2007;35(4):533–8.

    CAS  PubMed  Google Scholar 

  27. Migoya EM, Stevens CH, Bergman AJ, et al. Effect of moderate hepatic insufficiency on the pharmacokinetics of sitagliptin. Can J Clin Pharmacol. 2009;16(1):e165–70.

    PubMed  Google Scholar 

  28. Bergman AJ, Cote J, Yi B, et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care. 2007;30(7):1862–4.

    CAS  PubMed  Google Scholar 

  29. Fraser I, Neufeld N, Fox LA, et al. Pharmacokinetics and pharmacodynamics of sitagliptin in adolescents with type 2 diabetes [abstract]. 73rd Annual Meeting of the American Diabetes Association; 21–25 June 2013; Chicago (IL).

  30. Herman GA, Mistry GC, Yi B, et al. Evaluation of pharmacokinetic parameters and dipeptidyl peptidase-4 inhibition following single doses of sitagliptin in healthy, young Japanese males. Br J Clin Pharmacol. 2011;71(3):429–36.

    CAS  PubMed  Google Scholar 

  31. Migoya E, Larson P, Bergman A, et al. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, does not affect the pharmacokinetics of ethinyl estradiol or norethindrone in healthy female subjects. J Clin Pharmacol. 2011;51(9):1319–25.

    CAS  PubMed  Google Scholar 

  32. 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.

    CAS  PubMed  Google Scholar 

  33. Cerra M, Luo WL, Li S, et al. Effect of simvastatin on the pharmacokinetics of sitagliptin. J Popul Ther Clin Pharmacol. 2012;19(3):e356–60.

    PubMed  Google Scholar 

  34. Migoya EM, Miller JL, Gutierrez M, et al. Bioequivalence of sitagliptin/metformin fixed-dose combination tablets and concomitant administration of sitagliptin and metformin in healthy adult subjects: a randomized, open-label, crossover study. Clin Drug Investig. 2010;30(12):855–66.

    CAS  PubMed  Google Scholar 

  35. Iwamoto Y, Taniguchi T, Nonaka K, et al. Dose-ranging efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus. Endocr J. 2010;57(5):383–94.

    CAS  PubMed  Google Scholar 

  36. Hanefeld M, Herman GA, Wu M, et al. Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes. Curr Med Res Opin. 2007;23(6):1329–39.

    CAS  PubMed  Google Scholar 

  37. Scott R, Wu M, Sanchez M, et al. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract. 2007;61(1):171–80.

    CAS  PubMed  Google Scholar 

  38. Aschner P, Kipnes MS, Lunceford JK, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29(12):2632–7.

    CAS  PubMed  Google Scholar 

  39. 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(5):1049–58.

    CAS  PubMed  Google Scholar 

  40. Mohan V, Yang W, Son HY, et al. Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea. Diabetes Res Clin Pract. 2009;83(1):106–16.

    CAS  PubMed  Google Scholar 

  41. Nonaka K, Kakikawa T, Sato A, et al. Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2008;79(2):291–8.

    CAS  PubMed  Google Scholar 

  42. Raz I, Hanefeld M, Xu L, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia. 2006;49(11):2564–71.

    CAS  PubMed  Google Scholar 

  43. Aschner P, Katzeff HL, Guo H, et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12(3):252–61.

    CAS  PubMed  Google Scholar 

  44. Iwamoto Y, Tajima N, Kadowaki T, et al. Efficacy and safety of sitagliptin monotherapy compared with voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind trial. Diabetes Obes Metab. 2010;12(7):613–22.

    CAS  PubMed  Google Scholar 

  45. 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(2):252–8.

    CAS  PubMed  Google Scholar 

  46. Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes andmoderate-to-severe chronic renal insufficiency. Diabetes Care. 2013;36(5):1067–73.

    PubMed  Google Scholar 

  47. 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(4):579–87.

    PubMed  Google Scholar 

  48. Arjona Ferreira JC, Engel SS, Guo H, et al. Consistency of the A1C-lowering effects of sitagliptin versus glipizide in patients with type 2 diabetes and chronic renal insufficiency across a variety of baseline characteristics [abstract no. 1089-P]. Diabetes. 2012;61 Suppl 1:A281.

    Google Scholar 

  49. Arjona Ferreira JC, Engel SS, Guo H, et al. Sitagliptin more effectively achieves a composite endpoint of a1c reduction, no body weight gain, and lack of hypoglycemia in patients with type 2 diabetes and renal insufficiency compared to glipizide [abstract no. 1009-P). Diabetes. 2012;61 Suppl 1:A258.

    Google Scholar 

  50. Chan JC, Scott R, Arjona Ferreira JC, et al. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab. 2008;10(7):545–55.

    CAS  PubMed  Google Scholar 

  51. Engel SS, Xu L, Golm GT, et al. Comparison of treatment with sitagliptin (SITA) or sulfonylurea (SU) in patients with type 2 diabetes mellitus (T2DM) and mild renal insufficiency [abstract]. 73rd Annual Meeting of the American Diabetes Association; 21–25 June 2013; Chicago (IL).

  52. Kubota A, Maeda H, Kanamori A, et al. Efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients. J Diabetes Investig. 2012;3(6):503–9.

    CAS  Google Scholar 

  53. Arase Y, Suzuki F, Suzuki Y, et al. Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus. Hepatol Res. 2011;41(6):524–9.

    CAS  PubMed  Google Scholar 

  54. Odawara M, Kadowaki T, Tajima N, et al. Long-term safety, tolerability, and efficacy of the dipeptidyl peptidase-4 inhibitor sitagliptin in Japanese patients with type 2 diabetes. Diabetol Int. 2011;2(2):94–105.

    Google Scholar 

  55. Goldstein BJ, Feinglos MN, Lunceford JK, et al. 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. 2007;30(8):1979–87.

    CAS  PubMed  Google Scholar 

  56. Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study. Curr Med Res Opin. 2009;25(3):569–83.

    CAS  PubMed  Google Scholar 

  57. Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12(5):442–51.

    CAS  PubMed  Google Scholar 

  58. Reasner C, Olansky L, Seck TL, et al. The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(7):644–52.

    CAS  PubMed  Google Scholar 

  59. Olansky L, Reasner C, Seck TL, et al. A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycaemic control versus metformin monotherapy due to a low rate of addition of antihyperglycaemic agents. Diabetes Obes Metab. 2011;13(9):841–9.

    CAS  PubMed  Google Scholar 

  60. Wainstein J, Katz L, Engel SS, et al. Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(5):409–18.

    CAS  PubMed  Google Scholar 

  61. Sitagliptin/metformin (Janumet) US prescribing information. 2013. http://www.merck.com/product/usa/pi_circulars/j/janumet/janumet_pi.pdf. Accessed 25 Jul 2013.

  62. Sitagliptin and metformin extended-release (Janumet XR) US prescribing information. 2013. http://www.merck.com/product/usa/pi_circulars/j/janumet_xr/janumet_xr_pi.pdf. Accessed 25 Jul 2013.

  63. Sitagliptin/metformin (Efficib) summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000896/WC500021374.pdf. Accessed 25 Jul 2013.

  64. Chwieduk CM. Sitagliptin/metformin fixed-dose combination: in patients with type 2 diabetes mellitus. Drugs. 2011;71(3):349–61.

    CAS  PubMed  Google Scholar 

  65. Yoon KH, Shockey GR, Teng R, et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycemic control and measures of β-cell function in patients with type 2 diabetes. Int J Clin Pract. 2011;65(2):154–64.

    CAS  PubMed  Google Scholar 

  66. Perez-Monteverde A, Seck T, Xu L, et al. Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naive patients with type 2 diabetes. Int J Clin Pract. 2011;65(9):930–8.

    CAS  PubMed  Google Scholar 

  67. Henry RR, Staels B, Fonseca VA, et al. Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone - a factorial study [abstract no. O-0597]. 21st World Diabetes Congress; 4–8 Dec 2011; Dubai.

  68. Charbonnel B, Karasik A, Liu J, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006;29(12):2638–43.

    CAS  PubMed  Google Scholar 

  69. Kadowaki T, Tajima N, Odawara M, et al. Addition of sitagliptin to ongoing metformin monotherapy improves glycemic control in Japanese patients with type 2 diabetes over 52 weeks. J Diabetes Investig. 2013;4(2):174–81.

    CAS  Google Scholar 

  70. Raz I, Chen Y, Wu M, et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes. Curr Med Res Opin. 2008;24(2):537–50.

    CAS  PubMed  Google Scholar 

  71. Yang W, Guan Y, Shentu Y, et al. The addition of sitagliptin to ongoing metformin therapy significantly improves glycemic control in Chinese patients with type 2 diabetes. J Diabetes. 2012;4(3):227–37.

    CAS  PubMed  Google Scholar 

  72. 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.

    CAS  PubMed  Google Scholar 

  73. Aschner P, Chan J, Owens DR, et al. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial. Lancet. 2012;379(9833):2262–9.

    CAS  PubMed  Google Scholar 

  74. 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(9739):431–9.

    PubMed  Google Scholar 

  75. Nauck MA, Meininger G, Sheng D, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007;9(2):194–205.

    CAS  PubMed  Google Scholar 

  76. Pratley RE, Nauck M, Bailey T, et al. 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 [Erratum appears in Lancet. 2010 Jul 24;376(9737):234]. Lancet. 2010;375(9724):1447–56.

    CAS  PubMed  Google Scholar 

  77. 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(7):540–9.

    CAS  PubMed  Google Scholar 

  78. Scott R, Loeys T, Davies MJ, et al. Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2008;10(10):959–69.

    CAS  PubMed  Google Scholar 

  79. 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.

    CAS  PubMed  Google Scholar 

  80. Best JH, Rubin RR, Peyrot M, et al. Weight-related quality of life, health utility, psychological well-being, and satisfaction with exenatide once weekly compared with sitagliptin or pioglitazone after 26 weeks of treatment. Diabetes Care. 2011;34(2):314–9.

    CAS  PubMed  Google Scholar 

  81. Pratley R, Nauck M, Bailey T, et al. One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract. 2011;65(4):397–407.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Pratley RE, Nauck MA, Bailey T, et al. Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes: a randomized, open-label trial. Diabetes Care. 2012;35(10):1986–93.

    CAS  PubMed  Google Scholar 

  83. Dobs AS, Goldstein BJ, Aschner P, et al. Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes. J Diabetes. 2013;5(1):68–79.

    CAS  PubMed  Google Scholar 

  84. Fonseca V, Staels B, Morgan IJD, et al. Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes. J Diabetes Complications. 2013;27(2):177–83.

    PubMed  Google Scholar 

  85. Kashiwagi A, Kadowaki T, Tajima N, et al. Sitagliptin added to treatment with ongoing pioglitazone for up to 52 weeks improves glycemic control in Japanese patients with type 2 diabetes. J Diabetes Investig. 2011;2(5):381–90.

    CAS  Google Scholar 

  86. Rosenstock J, Brazg R, Andryuk PJ, et al. 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. 2006;28(10):1556–68.

    CAS  PubMed  Google Scholar 

  87. Hermansen K, Kipnes M, Luo E, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007;9(5):733–45.

    CAS  PubMed  Google Scholar 

  88. Round E, Shentu Y, Golm GT, et al. Safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control [abstract]. 73rd Annual Meeting of the American Diabetes Association; 21–25 June. 2013; Chicago (IL).

  89. Tajima N, Kadowaki T, Odawara M, et al. Addition of sitagliptin to ongoing glimepiride therapy in Japanese patients with type 2 diabetes over 52 weeks leads to improved glycemic control. Diabetol Int. 2011;2(1):32–44.

    Google Scholar 

  90. Kadowaki T, Tajima N, Odawara M, et al. Addition of sitagliptin, an oral, highly-selective dipeptidyl peptidase-4 inhibitor, improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes on insulin monotherapy. Diabetes. 2011;60:A279–80.

    Google Scholar 

  91. Vilsboll T, Rosenstock J, Yki-Jarvinen H, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12(2):167–77.

    CAS  PubMed  Google Scholar 

  92. Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother. 2013;14(15):2047–58.

    CAS  PubMed  Google Scholar 

  93. Engel SS, Round E, Golm GT, et al. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies (Erratum appears in Diabetes Ther. 2013;4(2):487). Diabetes Ther. 2013;4(1):119–45.

    PubMed Central  PubMed  Google Scholar 

  94. Eurich DT, Simpson S, Senthilselvan A, et al. Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ. 2013;346:f2267.

    CAS  PubMed Central  PubMed  Google Scholar 

  95. 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(7):984–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011;141(1):150–6.

    CAS  PubMed  Google Scholar 

  97. 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.

    CAS  PubMed  Google Scholar 

  98. 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(4):1019–27.

    CAS  PubMed  Google Scholar 

  99. 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(11):2349–54.

    CAS  PubMed  Google Scholar 

  100. Monami M, Dicembrini I, Martelli D, et al. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011;27 Suppl 3:57–64.

    CAS  PubMed  Google Scholar 

  101. Singh S, Chang H-Y, 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(7):534–9.

    CAS  PubMed  Google Scholar 

  102. Brodovicz KG, Engel SS, Thornberry NA. Glucagon-like peptide 1-based drugs and pancreatic safety [letter]. JAMA Intern Med. 2013;173(19):1842–3.

    CAS  PubMed  Google Scholar 

  103. Scheen A. Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis. Expert Opin Drug Saf. 2013;12(4):545–57.

    CAS  PubMed  Google Scholar 

  104. Pollack A. European regulator finds little risk in diabetes drugs. 2013. http://www.nytimes.com/2013/07/27/business/european-regulator-finds-little-risk-in-diabetes-drugs.html?_r=1. Accessed 11 Sept 2013.

  105. 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(1):3.

    CAS  PubMed Central  PubMed  Google Scholar 

  106. 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.

    CAS  PubMed  Google Scholar 

  107. 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.

    CAS  PubMed  Google Scholar 

  108. Scheen AJ. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med. 2013;125(3):7–20.

    PubMed  Google Scholar 

  109. Bloomfield DM, Krishna R, Hreniuk D, et al. A thorough QTc study to assess the effect of sitagliptin, a DPP4 inhibitor, on ventricular repolarization in healthy subjects. J Clin Pharmacol. 2009;49(8):937–46.

    CAS  PubMed  Google Scholar 

  110. Pendergrass M, Fenton C, Haffner SM, et al. Exenatide and sitagliptin are not associated with increased risk of acute renal failure: a retrospective claims analysis. Diabetes Obes Metab. 2012;14(7):596–600.

    CAS  PubMed  Google Scholar 

  111. Glactiv (sitagliptin phosphate hydrate tablets): Japanese prescribing information. Osaka: Ono Pharmaceutical Co., Ltd. 2013.

  112. Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs. 2012;72(17):2289–312.

    CAS  PubMed  Google Scholar 

  113. Deeks ED. Linagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2012;72(13):1793–824.

    CAS  PubMed  Google Scholar 

  114. Tahrani AA, Bailey CJ, Del Prato S, et al. Management of type 2 diabetes: new and future developments in treatment. Lancet. 2011;378(9786):182–97.

    CAS  PubMed  Google Scholar 

  115. Barnett AH. New treatments in type 2 diabetes: a focus on the incretin-based therapies. Clin Endocrinol (Oxf). 2009;70(3):343–53.

    CAS  PubMed  Google Scholar 

  116. Burgmaier M, Heinrich C, Marx N. Cardiovascular effects of GLP-1 and GLP-1-based therapies: implications for the cardiovascular continuum in diabetes? Diabet Med. 2013;30(3):289–99.

    CAS  PubMed  Google Scholar 

  117. Peters AL. Patient and treatment perspectives: revisiting the link between type 2 diabetes, weight gain, and cardiovascular risk. Cleve Clin J Med. 2009;76 Suppl 5:S20–7.

    PubMed  Google Scholar 

  118. Schwarz B, Gouveia M, Chen J, et al. Cost-effectiveness of sitagliptin-based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy. Diabetes Obes Metab. 2008;10 Suppl 1:43–55.

    CAS  PubMed  Google Scholar 

  119. Lage MJ, Fabunmi R, Boye KS. Comparison of costs among patients with type 2 diabetes treated with exenatide or sitagliptin therapy. Adv Ther. 2009;26:217–29.

    PubMed  Google Scholar 

  120. Langer J, Hunt B, Valentine WJ. Evaluating the short-term cost-effectiveness of liraglutide versus sitagliptin in patients with type 2 diabetes failing metformin monotherapy in the United States. J Manag Care Pharm. 2013;19:237–46.

    PubMed  Google Scholar 

  121. Kaltenboeck A, Ivanova J, Thomas N, et al. Health care resource use and costs in patients with type 2 diabetes mellitus after treatment initiation with saxagliptin or sitagliptin [abstract no. PDB31]. Value Health. 2013;16(3):A161.

    Google Scholar 

  122. Hutchings A, Tolley K, Achana F, et al. Cost-effectiveness of saxagliptin compared to sitagliptin for the treatment of patients with type 2 diabetes mellitus (T2DM) [abstract no. PDB39]. Value Health. 2011;14(7):A478.

    Google Scholar 

  123. Romero M, Marrugo R, Sanchez O, et al. Cost-effectiveness analysis of using hypoglycemic agents (linagliptin, saxagliptin, sitagliptin, vildagliptin, glimepiride and glibenclamide) with metformin in diabetes in Colombia [abstract no. PDB44]. Value Health. 2013;16(3):A163.

    Google Scholar 

  124. Wilson BP, Beaudet A, Caputo J, et al. Projected long-term clinical and economic outcomes of exenatide once weekly versus sitagliptin for the treatment of Type 2 diabetes in the UK [abstract no. P371]. Diabet Med. 2012;29 Suppl 1:142.

    Google Scholar 

  125. Schlander M, Mentrup S, Lund N. Addition of incretin-therapy to metformin in type-2-diabetes mellitus (T2DM): cost-effectiveness of liraglutide versus sitagliptin from the perspective of the German statutory health insurance (SHI) [abstract no. PDB38]. Value Health. 2010;13(7):A290.

    Google Scholar 

  126. Aledort Gaebler J, Samyshkin Y, Guillermin ALG, et al. Long-term cost-consequence analysis of exenatide once weekly versus sitagliptin or pioglitazone in type 2 diabetes patients in the United States [abstract no. PDB36]. Value Health. 2010;13 (7):A290.

    Google Scholar 

  127. Lee WC, Samyshkin Y, Langer J, et al. Long-term clinical and economic outcomes associated with liraglutide versus sitagliptin therapy when added to metformin in the treatment of type 2 diabetes: a CORE Diabetes Model analysis. J Med Econ. 2012;15 Suppl 2:28–37.

    CAS  PubMed  Google Scholar 

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes based on any comments received were made by the author on the basis of scientific and editorial merit.

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    Greg L. Plosker

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The manuscript was reviewed by: D.T. Eurich, Department of Public Health, School of Public Health, University of Alberta, Edmonton, AB, Canada; I. Raz, Diabetes Unit, Department of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel; A.J. Scheen, Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, CHU Liège, University of Liège, Liège, Belgium.

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Plosker, G.L. Sitagliptin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus. Drugs 74, 223–242 (2014). https://doi.org/10.1007/s40265-013-0169-1

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