Skip to main content

Advertisement

SpringerLink
Log in

The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a Bayesian network meta-analysis of 58 randomized controlled trials

  • Review Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Aims

The aim is to evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4-I: sitagliptin, saxagliptin, linagliptin, vildagliptin and alogliptin) in patients with type 2 diabetes.

Methods

We searched the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), and the Wanfang Database from inception to April, 2018. Randomized controlled trials were included if they compared the different versions of DPP4-I with each other or with placebo in treatment of type 2 diabetes. Bayesian network meta-analysis and pairwise meta-analysis were performed to evaluate the efficacy and safety of the different kinds of DPP4-I and placebo. The data were analyzed using STATA 12.0 and WinBUGS1.4 software.

Results

We identified 58 eligible studies (with 31356 patients) involving 14 treatment arms. Indirect comparison results showed that except for alogliptin, a decrease was found for all DPP4-I versus the placebo for hemoglobin A1c (HbA1c) with vildagliptin50 twice daily (BID) showing the highest probability. Linagliptin5 once daily (QD) decreased the level of fasting plasma glucose (FPG) the most for all DPP4-I versus the placebo; when comparing them with each other, alogliptin25QD was more effective when compared with sitagliptin100QD and vildaglipti50BID; linagliptin5qd had the highest decrease impact on body mass index (BMI). Except for hypoglycemia and upper respiratory tract infection (URTI), there are no statistical significance on incidence of adverse events and the body weight when DPP4-I are compared with each other or with placebo.

Conclusion

Our network meta-analysis presents the associations of DPP4-I versus placebos on HbA1c, FPG, 2 h postprandial blood glucose (2HPPG), BMI, body weight and adverse events. DPP4-I have a lowering effect on the glycemic level (HbA1c, FPG), especially vildaglipti50BID and linagliptin10QD, respectively. Besides, linagliptin5QD has the greatest probabilities of reducing BMI. In addition, DPP4-I were associated with not increasing the incidence of adverse events. Among them, vildagliptin100QD and sitagliptin100QD have the lowest probability in reducing the incidence of hypoglycemia and URTI, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Diabetes facts and figures. Brussels. International Diabetes Federation (2018). https://www.idf.org/ news/94:new-idf-figures-show-continued -increase-in-diabetes-across-the-globe,-reiterating-the-need-for-urgent-action.html. Accessed 1 Jan 2018

  2. International Diabetes Federation. IDFDIABETESATLAS, 7th edn. http://www.idf.org/files/idf_publications/idf_diabetes_atlas_EN/idf_diabetes_atlas_EN/assets/common/downloads/publication.pdf. Accessed 01 Jan 2018

  3. Deacon CF (2011) Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 13:17–18

    Article  Google Scholar 

  4. Holst JJ, Deacon CF (1998) Inhibition of the activity of dipeptidyl peptidase IV as a treatment for type 2 diabetes. Diabetes 47:1663–1670

    Article  PubMed  CAS  Google Scholar 

  5. Thornberry NA, Weber AE (2007) Discovery of JANUVIA (sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Curr Top Med Chem 7:557–568

    Article  PubMed  CAS  Google Scholar 

  6. Tahrani AA, Piya MK, Barnett AH (2009) Saxagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Adv Ther 26:249–262

    Article  PubMed  CAS  Google Scholar 

  7. Ckhardt ME, Angkop EL, Mark M et al (2007) 8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl) methyl]-3, 7-dihydro-1H-purine-2, 6-dione a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type-2 diabetes. Med Chem 50:6450–6453

    Article  CAS  Google Scholar 

  8. Feng J, Zhang ZY, Wallace MB (2007) Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. Med Chem 50:2297–2300

    Article  CAS  Google Scholar 

  9. Gerrald KR, Van SE, Wines RC et al (2012) Saxagliptin and sitagliptin in adult patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 14(6):481–492

    Article  PubMed  CAS  Google Scholar 

  10. Wan LY, Zhang C, Guo WH et al (2013) Efficacy and safety of sitagliptin in patients with type 2 diabetes mellitus: a meta-analysis. Advers Drug React J 15(6):306–313

    Google Scholar 

  11. Ying L, Yu MZ, Xu XZ et al (2015) Efficacy and safety of linagliptin for type 2 diabetes mellitus: a meta-analysis. Chin J Evid Based Med 15(9):1068–1077

    Google Scholar 

  12. Bafeta A, Trinquart L, Seror R, Ravaud P (2014) Reporting of results from network meta-analyses: methodological systematic review. BMJ 348:g1741

    Article  PubMed  PubMed Central  Google Scholar 

  13. Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [EB/OL]. The Cochrane Collaboration. http://www.cochrane-handbook.org. Accessed 3 Feb 2018

  14. Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chaimani A, Higgins JP, Mavridis D et al (2013) Graphical tools for network meta-analysis in STATA. PLoS One 8:e76654

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Higgins JP, Altman DG (2008) Assessing risk of bias in included studies[M]/Cochrane handbook for systematic reviews of interventions: Cochrane book series. John Wiley, Hoboken, pp 187–241

    Book  Google Scholar 

  17. Dersimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28(2):105

    Article  PubMed  Google Scholar 

  18. Hartung J, Knapp G (2001) A refined method for the meta-analysis of controlled clinical trials with binary outcome. Stat Med 20:3875–3889

    Article  PubMed  CAS  Google Scholar 

  19. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  20. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bulpitt C (1988) Subgroup analysis. Lancet 332(8601):31–34

    Article  Google Scholar 

  22. Valkenhoef GV, Kuiper J (2016) Network meta-analysis using bayesian methods[M]/evidence synthesis for decision making in healthcare. John Wiley, Hoboken, pp 76–93

    Google Scholar 

  23. Lu G, Ades AE (2004) Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 23:3105–3124

    Article  PubMed  CAS  Google Scholar 

  24. Dias S, Sutton AJ, Ades AE et al (2013) Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network metaanalysis of randomized controlled trials. Med Decis Making 33:607–617

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gelman A, Rubin DB (1992) Inference from iterative simulation using multiple sequences. Stat Sci 7:457–472

    Article  Google Scholar 

  26. Salanti G, Ades AE, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64(2):163–171

    Article  PubMed  Google Scholar 

  27. Donegan S, Williamson P, D’Alessandro U, Tudur-Smith C (2013) Assessing key assumptions of network meta-analysis: a review of methods. Res Synth Methods 4:291–323

    Article  PubMed  Google Scholar 

  28. Spiegelhalter DJ, Best NG, Carlin BP, Van Der Linde A (2002) Bayesian measures of model complexity an fit. J R Stat Soc Ser B (Stat Methodol) 64:583–639

    Article  Google Scholar 

  29. Tian JH, Zhang J, Ge L, Yang KH, Song FJ (2017) The methodological and reporting quality of systematic reviews from China and the USA are similar. J Clin Epidemiol 85:50–58

    Article  PubMed  Google Scholar 

  30. Xiaoyan C, Jing W, Xiaochun H, Yuyu T, Shunyou D, Yingyu F (2016) Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea. Curr Med Res Opin 6:1–6

    Google Scholar 

  31. Koyanagawa N, Miyoshi H, Ono K et al (2016) Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus. Endocr J 63(8):747

    Article  PubMed  CAS  Google Scholar 

  32. Asti A, D’Alessandro A, Zito FP et al (2016) Sitagliptin versus saxagliptin in decompensated type 2 diabetes mellitus patients. Italian J Med 10(1):36

    Article  CAS  Google Scholar 

  33. Huang HH, Xu WQ et al (2015) Comparative study on the efficacy of saxagliptin and vildagliptin in treating type 2 diabetes mellitus. Jiangxi Med J 2015(9):859–860

    Google Scholar 

  34. Chen P (2015) Clinical efficacy of DPP-IV inhibitor combined with metformin on type 2 diabetes mellitus. North Pharmaceutical (9):88–89

  35. Tang YZ, Wang G, Jiang ZH et al (2015) Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent. Diabetol Metab Syndrome 7(1):91

    Article  CAS  Google Scholar 

  36. Kothny W, Lukashevich V, Foley JE et al (2015) Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial. Diabetologia 58(9):2020–2026

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Göke R, Eschenbach P, Dütting ED (2015) Efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose: results of a randomized controlled trial. Diabetes Metabol 41(3):244–247

    Article  CAS  Google Scholar 

  38. Li LY, He X, Xie M et al (2014) Comparative study on the efficacy of Sitagliptin and saxagliptin in treating type 2 diabetes mellitus. 14(6):11–12.

  39. Takihata M, Nakamura A, Terauchi Y et al (2014) Comparative study of three DPP-4 inhibitors, namely sitagliptin, vildagliptin, and alogliptin, in Japanese type 2 diabetic patients: the cosva randomized, controlled trial. Clin Diabetes Ther Posters 106:1024

    Google Scholar 

  40. Li CJ, Yu Q, Yu P et al (2014) Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes. Exp Clin Endocrinol Diabetes 122(8):469

    Article  PubMed  CAS  Google Scholar 

  41. Sakamoto M, Nishimura R, Irako T et al (2012) Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): crossover pilot study (J-VICTORIA study). Cardiovasc Diabetol 11(1):92

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Rizzo MR, Barbieri M, Marfella R, Paolisso G (2012) Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Pathophysiol Complicat 35(10):2076–2082

    CAS  Google Scholar 

  43. Guerci B, Monnier L, Serusclat P et al (2012) Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized optima study. Diabetes Metab 38(4):359–366

    Article  PubMed  CAS  Google Scholar 

  44. Wang W, Yang J, Yang G et al (2016) 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 8(2):229

    Article  PubMed  CAS  Google Scholar 

  45. Yang W, Xing X, Lv X et al (2015) Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus. J Diabetes 7(2):174

    Article  PubMed  CAS  Google Scholar 

  46. Sheu WHH, Park SW, Yan G et al (2015) Linagliptin improves glycemic control after 1 year as add-on therapy to basal insulin in Asian patients with type 2 diabetes mellitus. Curr Med Res Opin 31(3):1–34

    Article  CAS  Google Scholar 

  47. Schmieder RE, Friedrich S, Kistner I et al (2015) Effects of linagliptin on early alterations of renal endothelial function in patients with type-2 diabetes. Nephrol Dial Transplant 30(suppl_3):iii11

    Article  Google Scholar 

  48. Chantal M, Ravi SR, Daniel L et al (2015) A randomized clinical trial to evaluate the efficacy and safety of co-administration of sitagliptin with intensively titrated insulin glargine. Diabetes Ther 6(2):127

    Article  CAS  Google Scholar 

  49. Leibowitz G, Cahn A, Bhatt DL et al (2015) Impact of treatment with saxagliptin on glycaemic stability and β-cell function in the SAVOR-TIMI 53 study. Diabetes Obes Metab 17(5):487

    Article  PubMed  CAS  Google Scholar 

  50. Laakso M, Rosenstock J, Groop PH et al (2015) Treatment with the dipeptidyl peptidase-4 inhibitor linagliptin or placebo followed by glimepiride in patients with type 2 diabetes with moderate to severe renal impairment: a 52-week, randomized, double-blind clinical trial. Diabetes Care 38(2):15–17

    Article  CAS  Google Scholar 

  51. Kohei K, Takashi K, Yasuo T et al (2015) Sitagliptin improves glycemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance. Diabetes Obes Metab 17:11

    Google Scholar 

  52. Wu YF (2013) The effect of saxagliptin monotherapy on treating new type 2 diabetes. Doctoral dissertation, Zhejiang University

  53. Yang W, Guan Y, Yue S et al (2012) The addition of sitagliptin to ongoing metformin therapy significantly improves glycemic control in Chinese patients with type 2 diabetes. J Diabetes 4(3):227–237

    Article  PubMed  CAS  Google Scholar 

  54. Rauch T, Graefe-Mody U, Deacon CF et al (2012) Linagliptin increases incretin levels, lowers glucagon, and improves glycemic control in type 2 diabetes mellitus. Diabetes Ther 3(1):10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Pan CY, Yang W, Tou C et al (2011) Efficacy and safety of saxagliptin in drug-naïve Asian patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Res Clin Pract 28(3):217–224

    Google Scholar 

  56. Pan C, Xing X, Han P et al (2012) Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus. Diabetes Obes Metab 14(8):737–744

    Article  PubMed  CAS  Google Scholar 

  57. Minervini G, Iqbal N, Charbonnel B et al (2012) Efficacy and safety of saxagliptin in combination with insulin in patients with long-standing type 2 diabetes. Intern Med J 61:A290

    Google Scholar 

  58. Kothny W, Shao Q, Groop P et al (2012) One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab 14(11):1032–1039

    Article  PubMed  CAS  Google Scholar 

  59. Kawamori R, Inagaki N, Araki E et al (2011) 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 14(4):348–357

    Article  Google Scholar 

  60. Gerosa D, Ragonesi PD, Anna C et al (2012) Vildagliptin action on some adipocytokine levels in type 2 diabetic patients: a 12-month, placebo-controlled study. Expert Opin Pharmacother 13(18):2581–2591

    Article  CAS  Google Scholar 

  61. Derosa G, Carbone A, Franzetti I et al (2012) Effects of a combination of sitagliptin plus metformin vs metformin monotherapy on glycemic control, β-cell function and insulin resistance in type 2 diabetic patients. Diabetes Res Clin Pract 98(1):51–60

    Article  PubMed  CAS  Google Scholar 

  62. Barnett A, Huisman H, Jones R et al (2012) Efficacy and safety of linagliptin in elderly patients (≥ 70 Years) with type 2 diabetes. Can J Diabetes 36(5):S39

    Article  Google Scholar 

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

    Article  Google Scholar 

  64. Seino Y, Fujita T, Hiroi S et al (2011) 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 27(9):1781–1792

    Article  PubMed  CAS  Google Scholar 

  65. Del PS, Barnett AH, Huisman H et al (2011) Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab 13(3):258

    Article  Google Scholar 

  66. Nowicki M, Rychlik I, Haller H et al (2011) Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab 13(6):523

    Article  PubMed  CAS  Google Scholar 

  67. Nowicki M, Rychlik I, Haller H et al (2011) Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment: a randomised controlled 52-week efficacy and safety study. Int J Clin Pract 65(12):1230

    Article  PubMed  CAS  Google Scholar 

  68. Mcgill JB, Sloan L, Newman J et al (2013) Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment. A 1-year, randomized, double-blind, placebo-controlled study. Diabetes Care 36(2):237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Lukashevich V, Schweizer A, Shao Q et al (2011) Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial. Diabetes Obes Metab 13(10):947–954

    Article  PubMed  CAS  Google Scholar 

  70. Lukashevich V, Schweizer A, Foley J, Shao Q, Groop PH, Kothny W et al (2011) Efficacy of vildagliptin therapy in combination with insulin in patients with type 2 diabetes and severe renal impairment. Diabetologia 54(Suppl1):S332

    Google Scholar 

  71. Kothny W, Schweizer A, Naik R, Groop PH, Shao Q, Lukashevich V et al (2011) Comparison of vildagliptin with placebo in a 24-week study of 221 patients with type 2 diabetes and severe renal impairment (eGFR < 30). Diabetologia. 54(Suppl1):S332

    Google Scholar 

  72. Newman J, Mcgill JB, Patel S, Friedrich C, Sauce C, Woerle HJ et al (2011) Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment. Diabetologia 54(Suppl1):S333

    Google Scholar 

  73. Horie Y, Kanada S, Watada H et al (2011) Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor linagliptin: a 4-week multicenter, randomized, double-blind, placebo-controlled phase IIa study in Japanese type 2 diabetes patients. Clin Ther 33(7):973

    Article  PubMed  CAS  Google Scholar 

  74. Dandona P, Makdissi A, Chang S et al (2011) Sitagliptin exerts an anti-inflammatory effect. Am Diabetes Assoc 60:A306

    Google Scholar 

  75. Barzilai N, Guo H, Mahoney EM et al (2011) Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin 27(5):1049–1058

    Article  PubMed  CAS  Google Scholar 

  76. Garber AJ, Foley JE, Banerji MA et al (2010) Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab 10(11):1047–1056

    Article  CAS  Google Scholar 

  77. Defronzo RA, Fleck PR, Wilson CA et al (2008) 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 31(12):2315–2317

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Chan JC, Scott R, Arjona Ferreira JC et al (2008) Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 10(7):545–555

    Article  PubMed  CAS  Google Scholar 

  79. Su Y, Lv LF, Li QZ, Zhao ZG (2014) A randomized controlled clinical trials for the treatment of type 2 diabetes by vildagliptin and alpha-glucosidase inhibitor. Chin J New Drugs 22:2655–2658

    Google Scholar 

  80. Lukashevich V, Kozlovski P, Foley J, Kothny W et al (2012) Vildagliptin combined with insulin reduces HBA1C without increasing risk of hypoglycemia and weight gain in patients with type 2 diabetes mellitus. Diabetes 61:A254

    Google Scholar 

  81. Moses RG, Kalra S, Brook D, Sockler J, Visvanathan J, Fisher SA (2012) Saxagliptin (SAXA) effectively reduces HbA1c and is well tolerated when added to a combination of metformin (MET) and sulfonylurea (SU). Clin Diabetes/Ther Posters 61:A282

    Google Scholar 

  82. Su Y, Lv LF, Li QZ, Zhao ZG, Su YL (2014) The clinical research on the treatment of type 2 diabetes mellitus by DPP-4 inhibitor. Chin J Diabetes 22(10):886–889

    CAS  Google Scholar 

  83. Ba J, Han P, Yuan G et al (2017) Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined with metformin. J Diabetes 09:667–676

    Article  CAS  Google Scholar 

  84. Pan C, Han P, Ji Q, li C, Lu J et al (2017) 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 09:386–395

    Article  CAS  Google Scholar 

  85. Shah A, Levesque K, Pierini E et al (2017) Effect of sitagliptin on glucose control in type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery. Diabetes Obes Metab 20:1–6

    CAS  Google Scholar 

  86. Tanaka K, Okada Y, Mori H et al (2017) Comparative analysis of the effects of alogliptin and vildagliptin on glucose metabolism in type 2 diabetes mellitus. Endocr J 64(2):179–189

    Article  PubMed  CAS  Google Scholar 

  87. Wang W, Ning G, Ma J et al (2017) A randomized clinical trial of the safety and efficacy of sitagliptin in patients with type 2 diabetes mellitus inadequately controlled by acarbose alone. Curr Med Res Opin 33(4):693–699

    Article  PubMed  CAS  Google Scholar 

  88. Sun F, Wu S, Guo S et al (2015) Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: a systematic review and network meta-analysis. Endocrine 48(3):794–803

    Article  PubMed  CAS  Google Scholar 

  89. Sun F, Wu S, Guo S et al (2015) Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis. Diabetes Res Clin Pract 10(1):26–37

    Article  CAS  Google Scholar 

  90. Jansen JP, Fleurence R, Devine B et al (2011) Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health 14(4):417–428

    Article  PubMed  Google Scholar 

  91. Cai L, Cai Y, Lu ZJ et al (2012) The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. J Clin Pharm Ther 37(4):386

    Article  PubMed  CAS  Google Scholar 

  92. Bekiari E, Rizava C, Athanasiadou E et al (2015) Systematic review and meta-analysis of vildagliptin for treatment of type 2 diabetes. Endocrine 52(3):458–480

    Article  PubMed  CAS  Google Scholar 

  93. Singhfranco D, Mclaughlinmiddlekauff J, Elrod S et al (2012) The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab 14(8):694–708

    Article  CAS  Google Scholar 

  94. Bryzinski BHB (2015) A pooled analysis of the efficacy and safety of saxagliptin as monotherapy in patients with type 2 diabetes. J Diabetes Metab 06:4

    Google Scholar 

  95. Shin S-J (2012) Glucagon-like peptide-1 receptor agonists and their effects on weight reduction. J Diabetes Investig 03:490–491

    Article  Google Scholar 

  96. Resnick HE, Valsania P, Halter JB et al (2000) Relation of weight gain and weight loss on subsequent diabetes risk in overweight adults. J Epidemiol Commun Health 54(8):596–602

    Article  CAS  Google Scholar 

  97. Ford ES, Williamson DF, Liu S (1997) Weight change and diabetes incidence: findings from a national cohort of US adults. Am J Epidemiol 146:214–222

    Article  PubMed  CAS  Google Scholar 

  98. Moghissi E, Ismailbeigi F, Devine RC (2013) Hypoglycemia: minimizing its impact in type 2 diabetes. Endocr Pract 19(3):1–33

    Article  Google Scholar 

  99. Mbanya JC, Al-Sifri S, Abdel-Rahim A et al (2015) Incidence of hypoglycemia in patients with type 2 diabetes treated with gliclazide versus DPP-4 inhibitors during Ramadan: a meta-analytical approach. Diabetes Res Clin Pract 109(2):226–232

    Article  PubMed  CAS  Google Scholar 

  100. Kim HM, Lim JS, Lee BW et al (2015) Optimal candidates for the switch from glimepiride to sitagliptin to reduce hypoglycemia in patients with type 2 diabetes mellitus. Endocrinol Metab 30(1):84–91

    Article  CAS  Google Scholar 

  101. Phung OJ, Scholle JM, Talwar M et al (2010) Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain and hypoglycemia in Type 2 diabetes. JAMA 303(14):1410–1418

    Article  PubMed  CAS  Google Scholar 

  102. Zhao Q, Hong D, Zheng D et al (2014) Risk of diarrhea in patients with type 2 diabetes mellitus treated with sitagliptin: a meta-analysis of 30 randomized clinical trials. Drug Des Dev Ther 8:2283

    CAS  Google Scholar 

  103. Bhattacharjee A, Gupta MC, Agrawal S (2016) Adverse drug reaction monitoring of newer oral anti-diabetic drugs—a pharmacovigilance perspective. Int J Pharmacol Res 6(04):142–151

    Google Scholar 

  104. Esposito K, Chiodini P, Maiorino MI et al (2014) Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term randomised controlled trials. BMJ Open 4(6):e005442–e005442

    Article  PubMed  PubMed Central  Google Scholar 

  105. Karagiannis T, Paschos P, Paletas K et al (2012) Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ 344:449–449

    Article  CAS  Google Scholar 

  106. Caldwell DM, Ades AE, Higgins JPT (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 331(7521):897–900

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the library of Lanzhou University for their database in accessing and acquiring the full texts. The authors are also grateful to the freelance editor for polishing and revising the language and the authors of the original studies included in this study.

Funding

No fund.

Author information

Author notes

  1. Juan Ling and Peng Cheng are co-first authors.

Authors and Affiliations

  1. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China

    Juan Ling, Long Ge, Jin-hui Tian, Xiu-xia Li, Jing-yun Zhang & Ke-hu Yang

  2. Key Laboratory of Evidence-based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, China

    Juan Ling, Long Ge, Jin-hui Tian, Xiu-xia Li, Jing-yun Zhang & Ke-hu Yang

  3. Chinese GRADE Center, Lanzhou University, Lanzhou, 730000, China

    Juan Ling, Long Ge, Jin-hui Tian, Xiu-xia Li, Jing-yun Zhang & Ke-hu Yang

  4. WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou, 730000, China

    Juan Ling, Long Ge, Jin-hui Tian, Xiu-xia Li, Jing-yun Zhang & Ke-hu Yang

  5. Department of Orthopedics, The Second Hospital of Lanzhou University, Lanzhou, China

    Peng Cheng

  6. First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China

    Long Ge

  7. Department of Endocrinology, Gansu Province Hospital of Traditional Chinese Medicine, Lanzhou, China

    Ding-hua Zhang

  8. Second Clinical Medical College of Lanzhou University, Lanzhou, 730000, China

    An-chen Shi

  9. School of Public Health of Lanzhou University, Lanzhou, 730000, Gansu, China

    Ya-jing Chen

Authors
  1. Juan Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Long Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ding-hua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. An-chen Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin-hui Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ya-jing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiu-xia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jing-yun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ke-hu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ke-hu Yang.

Ethics declarations

Conflict of interest

The authors have indicated that they have no conflict of interest regarding the content of this article.

Human and animal rights statement

This article is based on previously conducted studies and does not contain any studies with animals and humans performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Additional information

Managed by Massimo Porta.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ling, J., Cheng, P., Ge, L. et al. The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a Bayesian network meta-analysis of 58 randomized controlled trials. Acta Diabetol 56, 249–272 (2019). https://doi.org/10.1007/s00592-018-1222-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-018-1222-z

Keywords

Search

Navigation