Top

Clinical Drug Investigation

Published in:

01-03-2017 | Systematic Review

Factors Related to the Glucose-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis Focusing on Ethnicity and Study Regions

Authors: Kayo Fujita, Masayuki Kaneko, Mamoru Narukawa

Published in: Clinical Drug Investigation | Issue 3/2017

Abstract

Background and objective

Several systematic reviews and meta-analyses have been conducted including an analysis to investigate the difference between ethnic groups in the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors. This study assessed the factors related to the glucose-lowering efficacy and explored potential differences among ethnicities; in particular, Japanese subjects were dealt separately from other Asian subjects.

Methods

A systematic literature search was conducted using the MEDLINE, EMBASE, Cochrane Central Register, Japan Medical Abstracts Society, and ClinicalTrials.gov databases. Electronically searchable study results from the US/EU/Japanese regulatory approval reviews were also used. The weighted mean difference (WMD) for glycosylated hemoglobin (HbA_1c) change from baseline in DPP-4 inhibitors compared with placebo was calculated. Heterogeneity was assessed by using the Q statistic and I ² statistic. Univariate and multivariate meta-regression analyses were performed.

Results

The literature search identified 79 studies with 91 arms and 25,095 patients. The WMD in the change from baseline of HbA_1c between the DPP-4 inhibitor group and placebo group was −0.695% (95% confidence interval −0.734 to −0.656) with considerable heterogeneity (I ² = 69.7%). In univariate meta-regression, factors including study duration, percentage of males, age, duration of diabetes mellitus, baseline HbA_1c values, body mass index, body weight, and percentage of Asian subjects showed associations with the glucose-lowering efficacy. Additionally, studies in Asian subjects, studies in Japanese subjects, and studies conducted in Japan showed relations when three classifications regarding ethnicity and study regions were applied. In multivariate meta-regression, studies in Japanese subjects/studies conducted in Japan as well as the baseline HbA_1c values were identified as influencing factors.

Conclusion

These identified factors—Japanese subjects/studies conducted in Japan and the baseline HbA_1c values—should be taken into account when planning and conducting future clinical studies.

World Health Organization. Global report on diabetes. 2016. http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf?ua=1&ua=1. Accessed 14 Jun 2016.

Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–49. doi:10.1016/j.diabres.2013.11.002.CrossRefPubMed

International Diabetes Federation. Diabetes atlas, seventh edition. 2015. http://www.diabetesatlas.org/component/attachments/?task=download&id=116. Accessed 14 Jun 2016.

Survey of the state of diabetes in Japan in 1997 [in Japanese]. 1997. http://www.mhlw.go.jp/toukei/kouhyo/indexkk_4_1.html. Accessed 14 Jun 2016.

National Health and Nutrition Survey Japan, 2012 [in Japanese]. 2012. http://www.mhlw.go.jp/bunya/kenkou/eiyou/h24-houkoku.html. Accessed 14 Jun 2016.

Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response. Diabetes Care. 2013;36(6):1789–96.CrossRefPubMedPubMedCentral

DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88(4):787–835. doi:10.1016/j.mcna.2004.04.013.CrossRefPubMed

Kim DJ, Lee MS, Kim KW, Lee MK. Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus. Metabolism. 2001;50(5):590–3. doi:10.1053/meta.2001.22558.CrossRefPubMed

Qian L, Xu L, Wang X, Fu X, Gu Y, Lin F, et al. Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation. Diabetes Metab Res Rev. 2009;25(2):144–9. doi:10.1002/dmrr.922.CrossRefPubMed

10.

Matsumoto K, Miyake S, Yano M, Ueki Y, Yamaguchi Y, Akazawa S, et al. Glucose tolerance, insulin secretion, and insulin sensitivity in nonobese and obese Japanese subjects. Diabetes Care. 1997;20(10):1562–8.CrossRefPubMed

11.

Fukushima M, Usami M, Ikeda M, Nakai Y, Taniguchi A, Matsuura T, et al. Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes. Metabolism. 2004;53(7):831–5.CrossRefPubMed

12.

Flatt PR, Bailey CJ, Green BD. Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes. Front Biosci. 2008;13:3648–60.CrossRefPubMed

13.

Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35(6):992–1019.CrossRefPubMed

14.

Seino Y, Kuwata H, Yabe D. Incretin-based drugs for type 2 diabetes: focus on East Asian perspectives. J Diabetes Investig. 2016;7(Suppl 1):102–9.CrossRefPubMedPubMedCentral

15.

Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM. 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(4):696–708. doi:10.1007/s00125-012-2827-3.CrossRefPubMed

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(11):1453–69. doi:10.1345/aph.1R041.CrossRefPubMed

17.

Monami M, Cremasco F, Lamanna C, Marchionni N, Mannucci E. Predictors of response to dipeptidyl peptidase-4 inhibitors: evidence from randomized clinical trials. Diabetes Metab Res Rev. 2011;27(4):362–72. doi:10.1002/dmrr.1184.CrossRefPubMed

18.

Esposito K, Cozzolino D, Bellastella G, Maiorino MI, Chiodini P, Ceriello A, et al. Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2011;13(7):594–603. doi:10.1111/j.1463-1326.2011.01380.x.CrossRefPubMed

19.

Esposito K, Chiodini P, Capuano A, Maiorino MI, Bellastella G, Giugliano D. Baseline glycemic parameters predict the hemoglobin A1c response to DPP-4 inhibitors: meta-regression analysis of 78 randomized controlled trials with 20,053 patients. Endocrine. 2014;46(1):43–51. doi:10.1007/s12020-013-0090-0.CrossRefPubMed

20.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. doi:10.1136/bmj.b2700.CrossRefPubMedPubMedCentral

21.

Kashiwagi A, Kasuga M, Araki E, Oka Y, Hanafusa T, Ito H, et al. International clinical harmonization of glycated hemoglobin in Japan: from Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J Diabetes Investig. 2012;3(1):39–40.CrossRefPubMedPubMedCentral

22.

R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2015. http://www.R-project.org/. Accessed 14 Jun 2016.

23.

DeFronzo RA, Fleck PR, Wilson CA, Mekki Q. Alogliptin Study 010 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diabetes Care. 2008;31(12):2315–7. doi:10.2337/dc08-1035.CrossRefPubMedPubMedCentral

24.

Nauck MA, Ellis GC, Fleck PR, Wilson CA, Mekki Q. 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. 2009;63(1):46–55. doi:10.1111/j.1742-1241.2008.01933.x.CrossRefPubMed

25.

Pratley RE, Reusch JE, Fleck PR, Wilson CA, Mekki Q. 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. 2009;25(10):2361–71. doi:10.1185/03007990903156111.CrossRefPubMed

26.

Pratley RE, Kipnes MS, Fleck PR, Wilson C, Mekki Q. 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. doi:10.1111/j.1463-1326.2008.01016.x.CrossRefPubMed

27.

Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, dose-ranging comparison with placebo, followed by a long-term extension study. Curr Med Res Opin. 2011;27(9):1781–92. doi:10.1185/03007995.2011.599371.CrossRefPubMed

28.

Kaku K, Itayasu T, Hiroi S, Hirayama M, Seino Y. Efficacy and safety of alogliptin added to pioglitazone in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label long-term extension study. Diabetes Obes Metab. 2011;13(11):1028–35. doi:10.1111/j.1463-1326.2011.01460.x.CrossRefPubMed

29.

Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K. Alogliptin plus voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension. Curr Med Res Opin. 2011;27(Suppl 3):21–9. doi:10.1185/03007995.2011.614936.CrossRefPubMed

30.

Seino Y, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. J Diabetes Investig. 2012;3(6):517–25. doi:10.1111/j.2040-1124.2012.00226.x.CrossRefPubMedPubMedCentral

31.

Seino Y, Miyata Y, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin added to metformin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. Diabetes Obes Metab. 2012;14(10):927–36. doi:10.1111/j.1463-1326.2012.01620.x.CrossRefPubMed

32.

Pan C, Han P, Ji Q, Li C, Lu J, Yang J, et al. Efficacy and safety of alogliptin in patients with type 2 diabetes mellitus: a multicentre randomized double-blind placebo-controlled phase 3 study in mainland China, Taiwan, and Hong Kong. J Diabetes. 2016;. doi:10.1111/1753-0407.12425 [Epub ahead of print].

33.

Forst T, Uhlig-Laske B, Ring A, Graefe-Mody U, Friedrich C, Herbach K, et al. Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled type 2 diabetes. Diabet Med. 2010;27(12):1409–19. doi:10.1111/j.1464-5491.2010.03131.x.CrossRefPubMed

34.

Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab. 2011;13(3):258–67. doi:10.1111/j.1463-1326.2010.01350.x.CrossRefPubMed

35.

Taskinen MR, Rosenstock J, Tamminen I, Kubiak R, Patel S, Dugi KA, et al. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2011;13(1):65–74. doi:10.1111/j.1463-1326.2010.01326.x.CrossRefPubMed

36.

Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med. 2011;28(11):1352–61. doi:10.1111/j.1464-5491.2011.03387.x.CrossRefPubMed

37.

Lewin AJ, Arvay L, Liu D, Patel S, von Eynatten M, Woerle HJ. Efficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(9):1909–19 e15. doi: 10.1016/j.clinthera.2012.07.008.

38.

Kawamori R, Inagaki N, Araki E, Watada H, Hayashi N, Horie Y, et al. Linagliptin monotherapy provides superior glycaemic control versus placebo or voglibose with comparable safety in Japanese patients with type 2 diabetes: a randomized, placebo and active comparator-controlled, double-blind study. Diabetes Obes Metab. 2012;14(4):348–57. doi:10.1111/j.1463-1326.2011.01545.x.CrossRefPubMed

39.

Ross SA, Rafeiro E, Meinicke T, Toorawa R, Weber-Born S, Woerle HJ. Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial. Curr Med Res Opin. 2012;28(9):1465–74. doi:10.1185/03007995.2012.714360.

40.

Haak T, Meinicke T, Jones R, Weber S, von Eynatten M, Woerle HJ. Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2012;14(6):565–74. doi:10.1111/j.1463-1326.2012.01590.x.CrossRefPubMed

41.

Barnett AH, Patel S, Harper R, Toorawa R, Thiemann S, von Eynatten M, et al. Linagliptin monotherapy in type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III trial with a 34-week active-controlled extension. Diabetes Obes Metab. 2012;14(12):1145–54. doi:10.1111/dom.12011.CrossRefPubMed

42.

Bajaj M, Gilman R, Patel S, Kempthorne-Rawson J. Lewis-D’Agostino D, Woerle HJ. Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study. Diabet Med. 2014;31(12):1505–14. doi:10.1111/dme.12495.CrossRefPubMedPubMedCentral

43.

Chen Y, Ning G, Wang C, Gong Y, Patel S, Zhang C, et al. Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: a multinational, 24-week, randomized, clinical trial. J Diabetes Investig. 2015;6(6):692–8. doi:10.1111/jdi.12346.CrossRefPubMedPubMedCentral

44.

Wang W, Yang J, Yang G, Gong Y, Patel S, Zhang C, et al. Efficacy and safety of linagliptin in Asian patients with type 2 diabetes mellitus inadequately controlled by metformin: a multinational 24-week, randomized clinical trial. J Diabetes. 2016;8(2):229–37. doi:10.1111/1753-0407.12284.CrossRefPubMed

45.

Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008;10(5):376–86. doi:10.1111/j.1463-1326.2008.00876.x.CrossRefPubMed

46.

Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R, et al. Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin. 2009;25(10):2401–11. doi:10.1185/03007990903178735.CrossRefPubMed

47.

DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009;32(9):1649–55. doi:10.2337/dc08-1984.CrossRefPubMedPubMedCentral

48.

Hollander P, Li J, Allen E, Chen R, 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. 2009;94(12):4810–9. doi:10.1210/jc.2009-0550.CrossRefPubMed

49.

Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R, et al. 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. 2009;63(9):1395–406. doi:10.1111/j.1742-1241.2009.02143.x.CrossRefPubMedPubMedCentral

50.

Yang W, Pan CY, Tou C, Zhao J, Gause-Nilsson I. Efficacy and safety of saxagliptin added to metformin in Asian people with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Res Clin Pract. 2011;94(2):217–24. doi:10.1016/j.diabres.2011.07.035.CrossRefPubMed

51.

Pan CY, Yang W, Tou C, Gause-Nilsson I, Zhao J. Efficacy and safety of saxagliptin in drug-naive Asian patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Metab Res Rev. 2012;28(3):268–75. doi:10.1002/dmrr.1306.CrossRefPubMed

52.

Frederich R, McNeill R, Berglind N, Fleming D, Chen R. The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naive patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetol Metab Syndr. 2012;4(1):36. doi:10.1186/1758-5996-4-36.CrossRefPubMedPubMedCentral

53.

White JL, Buchanan P, Li J, Frederich R. A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy. BMC Endocr Disord. 2014;14:17. doi:10.1186/1472-6823-14-17.CrossRefPubMedPubMedCentral

54.

Moses RG, Kalra S, Brook D, Sockler J, Monyak J, Visvanathan J, et al. A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea. Diabetes Obes Metab. 2014;16(5):443–50. doi:10.1111/dom.12234.CrossRefPubMed

55.

Seino Y. Efficacy and safety of saxagliptin in Japanese patients with type 2 diabetes—two multi-centre, randomized, double-blind, placebo-controlled studies [in Japanese]. Jpn Pharmacol Ther. 2014;42(7):503–18.

56.

Matthaei S, Catrinoiu D, Celiński A, Ekholm E, Cook W, Hirshberg B, et al. Randomized, double-blind trial of triple therapy with saxagliptin add-on to dapagliflozin plus metformin in patients with type 2 diabetes. Diabetes Care. 2015;38(11):2018–24. doi:10.2337/dc15-0811.CrossRefPubMed

57.

AstraZeneca. Evaluate saxagliptin in adult indian patients with type 2 diabetes inadequate glycemic control [ClinicalTrials.gov identifier NCT00918879]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT00918879?term=NCT00918879&rank=1. Accessed 7 Jul 2016.

58.

Ristic S, Byiers S, Foley J, Holmes D. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab. 2005;7(6):692–8. doi:10.1111/j.1463-1326.2005.00539.x.CrossRefPubMed

59.

Dejager S, Razac S, Foley JE, Schweizer A. Vildagliptin in drug-naive patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study. Horm Metab Res. 2007;39(3):218–23. doi:10.1055/s-2007-970422.CrossRefPubMed

60.

Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetes. Diabetes Res Clin Pract. 2007;76(1):132–8. doi:10.1016/j.diabres.2006.12.009.CrossRefPubMed

61.

Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care. 2007;30(4):890–5. doi:10.2337/dc06-1732.CrossRefPubMed

62.

Garber AJ, Schweizer A, Baron MA, Rochotte E, Dejager S. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study. Diabetes Obes Metab. 2007;9(2):166–74. doi:10.1111/j.1463-1326.2006.00684.x.CrossRefPubMed

63.

Garber AJ, Foley JE, Banerji MA, Ebeling P, Gudbjornsdottir S, Camisasca RP, et al. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab. 2008;10(11):1047–56. doi:10.1111/j.1463-1326.2008.00859.x.CrossRefPubMed

64.

Kikuchi M, Abe N, Kato M, Terao S, Mimori N, Tachibana H. Vildagliptin dose-dependently improves glycemic control in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2009;83(2):233–40. doi:10.1016/j.diabres.2008.10.006.CrossRefPubMed

65.

Kikuchi M, Haneda M, Koya D, Tobe K, Onishi Y, Couturier A, et al. Efficacy and tolerability of vildagliptin as an add-on to glimepiride in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2010;89(3):216–23. doi:10.1016/j.diabres.2010.04.017.CrossRefPubMed

66.

Kikuchi M, Iwamoto Y, Inagaki N, Yoshioka T, Mimori N, Ebina H. Clinical evaluation of vildagliptin in patients with type 2 diabetes [in Japanese]. J New Rem Clin. 2010;59(2):121–36.

67.

Pan C, Xing X, Han P, Zheng S, Ma J, Liu J, et al. Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2012;14(8):737–44. doi:10.1111/j.1463-1326.2012.01593.x.CrossRefPubMed

68.

Odawara M, Hamada I, Suzuki M. Efficacy and safety of vildagliptin as add-on to metformin in Japanese patients with type 2 diabetes mellitus. Diabetes Ther. 2014;5(1):169–81. doi:10.1007/s13300-014-0059-x.CrossRefPubMedPubMedCentral

69.

Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H, 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. doi:10.1007/s00125-006-0416-z.CrossRefPubMed

70.

Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE, 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. doi:10.2337/dc06-0703.CrossRefPubMed

71.

Charbonnel B, Karasik A, Liu J, Wu M. Meininger G; Sitagliptin Study 020 Group. 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. doi:10.2337/dc06-0706.CrossRefPubMed

72.

Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. 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. doi:10.1016/j.clinthera.2006.10.007.CrossRefPubMed

73.

Hanefeld M, Herman GA, Wu M, Mickel C, Sanchez M, Stein PP, 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. doi:10.1185/030079907X188152.CrossRefPubMed

74.

Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE, Sitagliptin 036 Study Group. 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. doi:10.2337/dc07-0627.CrossRefPubMed

75.

Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P, 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. doi:10.1111/j.1463-1326.2007.00744.x.CrossRefPubMed

76.

Scott R, Wu M, Sanchez M, Stein P. 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. doi:10.1111/j.1742-1241.2006.01246.x.CrossRefPubMed

77.

Raz I, Chen Y, Wu M, Hussain S, Kaufman KD, Amatruda JM, 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. doi:10.1185/030079908X260925.CrossRefPubMed

78.

Scott R, Loeys T, Davies MJ, Engel SS. Sitagliptin Study 801 Group. 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. doi:10.1111/j.1463-1326.2007.00839.x.CrossRefPubMed

79.

Nonaka K, Kakikawa T, Sato A, Okuyama K, Fujimoto G, Kato N, et al. Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2008;79(2):291–8. doi:10.1016/j.diabres.2007.08.021.CrossRefPubMed

80.

Mohan V, Yang W, Son HY, Xu L, Noble L, Langdon RB, 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. doi:10.1016/j.diabres.2008.10.009.CrossRefPubMed

81.

Iwamoto Y, Taniguchi T, Nonaka K, Okamoto T, Okuyama K, Arjona Ferreira JC, 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.CrossRefPubMed

82.

Kashiwagi A, Kadowaki T, Tajima N, Nonaka K, Taniguchi T, Nishii M, 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. doi:10.1111/j.2040-1124.2011.00120.x.CrossRefPubMedPubMedCentral

83.

Barzilai N, Guo H, Mahoney EM, Caporossi S, Golm GT, Langdon RB, 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. doi:10.1185/03007995.2011.568059.CrossRefPubMed

84.

Tajima N, Kadowaki T, Odawara M, Nishii M, Taniguchi T, Arjona Ferreira JC. 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. doi:10.1007/s13340-011-0022-2.CrossRef

85.

Yang W, Guan Y, Shentu Y, Li Z, Johnson-Levonas AO, Engel SS, 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. doi:10.1111/j.1753-0407.2012.00213.x.CrossRefPubMed

86.

Nicolle LE, Capuano G, Ways K, Usiskin K. Effect of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on bacteriuria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week, phase 2 study. Curr Med Res Opin. 2012;28(7):1167–71. doi:10.1185/03007995.2012.689956.CrossRefPubMed

87.

Fonseca V, Staels B, Morgan JD 2nd, Shentu Y, Golm GT, Johnson-Levonas AO, 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. doi:10.1016/j.jdiacomp.2012.09.007.CrossRefPubMed

88.

Dobs AS, Goldstein BJ, Aschner P, Horton ES, Umpierrez GE, Duran L, 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. doi:10.1111/j.1753-0407.2012.00223.x.CrossRefPubMed

89.

Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle HJ, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013;1(3):208–19. doi:10.1016/s2213-8587(13)70084-6.CrossRefPubMed

90.

Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013;56(12):2582–92. doi:10.1007/s00125-013-3039-1.CrossRefPubMedPubMedCentral

91.

Tajima N, Kadowaki T, Okamoto T, Sato A, Okuyama K, Minamide T, et al. Sitagliptin added to voglibose monotherapy improves glycemic control in patients with type 2 diabetes. J Diabetes Investig. 2013;4(6):595–604. doi:10.1111/jdi.12116.CrossRefPubMedPubMedCentral

92.

Kadowaki T, Tajima N, Odawara M, Nishii M, Taniguchi T, Ferreira JC. 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. doi:10.1111/jdi.12001.CrossRefPubMed

93.

Amin NB, Aggarwal N, Pall D, Paragh G, Denney WS, Le V, et al. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015;17(8):751–9. doi:10.1111/dom.12474.CrossRefPubMed

94.

Ji L, Han P, Wang X, Liu J, Zheng S, Jou YM, et al. Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus. J Diabetes Investig. 2016;7(5):727–36. doi:10.1111/jdi.12511.CrossRefPubMedPubMedCentral

95.

Moses RG, Round E, Shentu Y, Golm GT, O’Neill EA, Gantz I, et al. A randomized clinical trial evaluating the safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control. J Diabetes. 2016;8(5):701–11. doi:10.1111/1753-0407.12351.CrossRefPubMed

96.

Merck Sharp & Dohme Corp. Clinical trial to evaluate the safety and efficacy of the addition of sitagliptin in participants with type 2 diabetes mellitus receiving acarbose monotherapy (MK-0431-130) [ClinicalTrials.gov identifier NCT01177384]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01177384?term=NCT01177384&rank=1. Accessed 7 Jul 2016.

97.

Boehringer Ingelheim/Eli Lilly and Company. Safety and efficacy of empagliflozin (BI 10773) and sitagliptin versus placebo over 76 weeks in patients with type 2 diabetes [ClinicalTrials.gov identifier NCT01289990]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01289990?term=NCT01289990&rank=1. Accessed 7 Jul 2016.

98.

Pfizer. Study of safety and efficacy of PF-04991532 in subjects with type 2 diabetes [ClinicalTrials.gov identifier NCT01338870]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01338870?term=NCT01338870&rank=1. Accessed 7 Jul 2016.

99.

Pfizer. Study of safety and efficacy of PF-04991532 in subjects with type 2 diabetes mellitus [ClinicalTrials.gov identifier NCT01336738]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01336738?term=NCT01336738&rank=1. Accessed 7 Jul 2016.

100.

Merck Sharp & Dohme Corp. A study in China evaluating the safety and efficacy of adding sitagliptin to stable therapy with sulfonylurea with or without metformin in participants with type 2 diabetes mellitus (T2DM) (MK-0431-253) [ClinicalTrials.gov identifier NCT01590771]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01590771?term=NCT01590771&rank=1. Accessed 7 Jul 2016.

101.

Merck Sharp & Dohme Corp. Omarigliptin (MK-3102) clinical trial – placebo- and sitagliptin-controlled monotherapy study in japanese patients with type 2 diabetes mellitus (MK-3102-020) [ClinicalTrials.gov identifier NCT01703221]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01703221?term=NCT01703221&rank=1. Accessed 7 Jul 2016.

102.

Bloomgarden ZT, Dodis R, Viscoli CM, Holmboe ES, Inzucchi SE. Lower baseline glycemia reduces apparent oral agent glucose-lowering efficacy: a meta-regression analysis. Diabetes Care. 2006;29(9):2137–9. doi:10.2337/dc06-1120.CrossRefPubMed

103.

Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011;13(1):7–18. doi:10.1111/j.1463-1326.2010.01306.x.CrossRefPubMed

104.

Singh AK. Incretin response in Asian type 2 diabetes: are Indians different? Indian J Endocrinol Metab. 2015;19(1):30–8. doi:10.4103/2230-8210.146861.CrossRefPubMedPubMedCentral

Title: Factors Related to the Glucose-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis Focusing on Ethnicity and Study Regions
Authors: Kayo Fujita
Masayuki Kaneko
Mamoru Narukawa
Publication date: 01-03-2017
Publisher: Springer International Publishing
Published in: Clinical Drug Investigation / Issue 3/2017
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI: https://doi.org/10.1007/s40261-016-0478-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Factors Related to the Glucose-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis Focusing on Ethnicity and Study Regions

Abstract

Background and objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2017

A Randomized, Single-Blind Trial of Clobetasol Propionate 0.05% Cream Under Silicone Dressing Occlusion Versus Intra-Lesional Triamcinolone for Treatment of Keloid

Effect of Multiple Oral Doses of the Potent CYP3A4 Inhibitor Clarithromycin on the Pharmacokinetics of a Single Oral Dose of Vonoprazan: A Phase I, Open-Label, Sequential Design Study

Safety and Effectiveness of Sodium Stibogluconate and Paromomycin Combination for the Treatment of Visceral Leishmaniasis in Eastern Africa: Results from a Pharmacovigilance Programme

Cost-Effectiveness Analysis of Apixaban, Dabigatran, Rivaroxaban, and Warfarin for Stroke Prevention in Atrial Fibrillation in Taiwan

Quantifying the Exposure of Tapentadol Extended Release in Japanese Patients with Cancer Pain and Bridging Tapentadol Pharmacokinetics Across Populations Using a Modeling Approach

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers