Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: Systematic review and meta-analysis of randomised and observational studies

The BMJ

Volumn 352, Issue , 2016, Pages

  Li, Ling ^a   Li, Sheyu ^a   Deng, Ke ^b   Liu, Jiali ^a   Vandvik, Per Olav ^c,d   Zhao, Pujing ^a   Zhang, Longhao ^a   Shen, Jiantong ^a   Bala, Malgorzata M ^e   Sohani, Zahra N ^f,g   Wong, Evelyn ^h   Busse, Jason W ^f,i   Ebrahim, Shanil ^f,j,k   Malaga, German ^l   Rios, Lorena P ^m   Wang, Yingqiang ⁿ   Chen, Qunfei ^o   Guyatt, Gordon H ^f   Sun, Xin ^a  

^a SICHUAN UNIVERSITY   (China)

^b SICHUAN UNIVERSITY   (China)

^c NORWEGIAN KNOWLEDGE CENTRE FOR THE HEALTH SERVICES   (Norway)

^d INNLANDET HOSPITAL TRUST   (Norway)

^e JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

^f MCMASTER UNIVERSITY   (Canada)

^g UNIVERSITY OF TORONTO   (Canada)

^h UNIVERSITY OF BRITISH COLUMBIA   (Canada)

ⁱ MCMASTER UNIVERSITY   (Canada)

^j STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k HOSPITAL FOR SICK CHILDREN   (Canada)

^l UNIVERSIDAD PERUANA CAYETANO HEREDIA   (Peru)

^m Hospital Clinico FUSAT   (Chile)

ⁿ Aviation Industry of China   (China)

^o LANZHOU UNIVERSITY   (China)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALOGLIPTIN; CANAGLIFLOZIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EMPAGLIFLOZIN; GLIBENCLAMIDE; GLIMEPIRIDE; GLIPIZIDE; HEMOGLOBIN A1C; INSULIN; LINAGLIPTIN; METFORMIN; PIOGLITAZONE; PLACEBO; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN; VOGLIBOSE; ANTIDIABETIC AGENT;

ADD ON THERAPY; ARTICLE; CONGESTIVE HEART FAILURE; DRUG SAFETY; HEART FAILURE; HEMOGLOBIN BLOOD LEVEL; HOSPITAL ADMISSION; HUMAN; META ANALYSIS; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBSERVATIONAL STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMATIC REVIEW; CARDIOVASCULAR DISEASE; CHEMICALLY INDUCED; COMPLICATION; DIABETES MELLITUS, TYPE 2; HOSPITALIZATION; ODDS RATIO; RISK FACTOR; STATISTICS AND NUMERICAL DATA;

CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HEART FAILURE; HOSPITALIZATION; HUMANS; HYPOGLYCEMIC AGENTS; OBSERVATIONAL STUDIES AS TOPIC; ODDS RATIO; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS;

EID: 84960100350     PISSN: 09598146     EISSN: 17561833     Source Type: Journal    
DOI: 10.1136/bmj.i610     Document Type: Article

References (119)

1. International Diabetes Federation. IDF DIABETES ATLAS (Sixth edition). http://www.idf.org/files/idf-publications/idf-diabetes-Atlas-EN/idf-diabetes-Atlas-EN/assets/common/downloads/publication.pdf (accessed May 8 2015).
2. Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-Analysis. BMJ 2012;344:e1369. doi:10.1136/bmj.e1369.
3. Esposito K, Chiodini P, Maiorino MI, Bellastella G, Capuano A, Giugliano D. Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and metaanalysis of long-term randomised controlled trials. BMJ Open 2014;4:e005442. doi:10.1136/bmjopen-2014-005442.
4. Kawalec P, Mikrut A, opuch S. The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-Analysis. Diabetes Metab Res Rev 2014;30:269-83. doi:10.1002/dmrr.2494.
5. Monami M, Ahrén B, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-Analysis of randomized clinical trials. Diabetes Obes Metab 2013;15:112-20. doi:10.1111/dom.12000.
6. Patil HR, Al Badarin FJ, Al Shami HA, et al. Meta-Analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol 2012;110:826-33. doi:10.1016/j. amjcard.2012.04.061.
7. Savarese G, Perrone-Filardi P, D'Amore C, et al. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in diabetic patients: A meta-Analysis. Int J Cardiol 2015;181:239-44. doi:10.1016/j. ijcard.2014.12.017.
8. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140-9. doi:10.2337/dc14-2441.
9. Scirica BM, Bhatt DL, Braunwald E, et al. SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317-26. doi:10.1056/NEJMoa1307684.
10. U.S. Food and Drug Administration. Saxagliptin (marketed as Onglyza and Kombiglyze XR): drug safety communication-FDA to review heart failure risk. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm385471.htm (accessed August 27 2015).
11. Zannad F, Cannon CP, Cushman WC, et al. EXAMINE Investigators. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet 2015;385:2067-76. doi:10.1016/S0140-6736(14)62225-X.
12. Green JB, Bethel MA, Armstrong PW, et al. TECOS Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2015;373:232-42. doi:10.1056/NEJMoa1501352.
13. Fadini GP, Avogaro A, Degli Esposti L, et al. OsMed Health-DB Network. Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database. Eur Heart J 2015;36:2454-62. doi:10.1093/eurheartj/ehv301.
14. Fu AZ, Johnston S, Sheehan J, et al. Risk of hospitalization for heart failure with dipeptidyl peptidase-4 inhibitors vs. sulfonylureas and with saxagliptin vs. sitagliptin in a U.S. claims database. American Diabetes Association 75th Scientific Sessions (2015): 164-LB-2015 [Board 164]. Presented on June 7, 2015.
15. Wang KL, Liu CJ, Chao TF, et al. Sitagliptin and the risk of hospitalization for heart failure: a population-based study. Int J Cardiol 2014;177:86-90. doi:10.1016/j.ijcard.2014.09.038.
16. Weir DL, McAlister FA, Senthilselvan A, Minhas-Sandhu JK, Eurich DT. Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study. JACC Heart Fail 2014;2:573-82. doi:10.1016/j.jchf.2014.04.005.
17. Yu OH, Filion KB, Azoulay L, Patenaude V, Majdan A, Suissa S. Incretin-based drugs and the risk of congestive heart failure. Diabetes Care 2015;38:277-84. doi:10.2337/dc14-1459.
18. Stroup DF, Berlin JA, Morton SC, et al. Meta-Analysis of observational studies in epidemiology: a proposal for reporting. Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008-12. doi:10.1001/jama.283.15.2008.
19. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-Analyses: the PRISMA statement. BMJ 2009;339:b2535. doi:10.1136/bmj.b2535.
20. ClinicalTrials.gov. Why should i register and submit results? https://www.clinicaltrials.gov/ct2/manage-recs/background (accessed August 25 2015).
21. U.S. Food and Drug Administration. Food and Drug Administration Amendments Act (FDAAA) of 2007. US Public Law 110-85 section 801. https://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf (accessed August 25 2015).
22. Higgins JPTAD, Sterne JAC. Assessing risk of bias in included studies. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0.Cochrane Collaboration, 2011.
23. Akl EA, Sun X, Busse JW, et al. Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid. J Clin Epidemiol 2012;65:262-7. doi:10.1016/j. jclinepi.2011.04.015.
24. Wells GASB, O'Connell D, Peterson J, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of non-randomized studies in meta-Analysis. http://www.ohri.ca/programs/clinical-epidemiology/oxford.asp (accessed August 25 2015).
25. Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0.Cochrane Collaboration, 2011.
26. Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A. Much ado about nothing: a comparison of the performance of meta-Analytical methods with rare events. Stat Med 2007;26:53-77. doi:10.1002/sim.2528.
27. Higgins JPTDJ, Altman DG. Special topics in statistics. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0.Cochrane Collaboration, 2011.
28. Guyatt GH, Oxman AD, Vist GE, et al. GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. doi:10.1136/bmj.39489.470347.AD.
29. Guyatt GH, Oxman AD, Vist G, et al. GRADE guidelines: 4. Rating the quality of evidence-study limitations (risk of bias). J Clin Epidemiol 2011;64:407-15. doi:10.1016/j.jclinepi.2010.07.017.
30. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines 6. Rating the quality of evidence-imprecision. J Clin Epidemiol 2011;64:1283-93. doi:10.1016/j.jclinepi.2011.01.012. 21839614.
31. Guyatt GH, Oxman AD, Kunz R, et al. GRADE Working Group. GRADE guidelines: 7. Rating the quality of evidence-inconsistency. J Clin Epidemiol 2011;64:1294-302. doi:10.1016/j.jclinepi.2011.03.017.
32. Guyatt GH, Oxman AD, Kunz R, et al. GRADE Working Group. GRADE guidelines: 8. Rating the quality of evidence-indirectness. J Clin Epidemiol 2011;64:1303-10. doi:10.1016/j.jclinepi.2011.04.014.
33. Guyatt GH, Oxman AD, Montori V, et al. GRADE guidelines: 5. Rating the quality of evidence-publication bias. J Clin Epidemiol 2011;64:1277-82. doi:10.1016/j.jclinepi.2011.01.011.
34. Guyatt GH, Oxman AD, Sultan S, et al. GRADE Working Group. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol 2011;64:1311-6. doi:10.1016/j.jclinepi.2011.06.004.
35. Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency. Diabetes Care 2013;36:1067-73. doi:10.2337/dc12-1365.
36. Merck. Sitagliptin versus glipizide in participants with type 2 diabetes mellitus and chronic renal insufficiency (MK-0431-063 AM1). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00509262.
37. Arjona Ferreira JC, Corry D, Mogensen CE, et al. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis 2013;61:579-87. doi:10.1053/j.ajkd.2012.11.043.
38. Merck. Sitagliptin versus glipizide in participants with type 2 diabetes mellitus and end-stage renal disease (MK-0431-073 AM1). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00509236.
39. Bosi E, Ellis GC, Wilson CA, Fleck PR. Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study. Diabetes Obes Metab 2011;13:1088-96. doi:10.1111/j.1463-1326. 2011.01463.x.
40. Ferrannini E, Fonseca V, Zinman B, et al. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Diabetes Obes Metab 2009;11:157-66. doi:10.1111/j.1463-1326. 2008.00994.x.
41. Fonseca V, Staels B, Morgan JD 2nd, 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;27:177-83. doi:10.1016/j.jdiacomp.2012.09.007.
42. 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;9:166-74. doi:10.1111/j.1463-1326.2006.00684.x.
43. Henry RR, Staels B, Fonseca VA, et al. Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone-A factorial study. Diabetes Obes Metab 2014;16:223-30. doi:10.1111/dom.12194.
44. Merck. MK0431 and pioglitazone co-Administration factorial study in patients with type 2 diabetes mellitus (0431-102 AM2). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00722371.
45. 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;57:383-94. doi:10.1507/endocrj.K09E-272.
46. Merck. A Study of an investigational drug sitagliptin for type 2 diabetes mellitus. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00127192.
47. Merck. An investigational drug study in patients with type 2 diabetes mellitus. National Library of Medicine (US), 2000. https://clinicaltrials. gov/show/NCT00094770.
48. Seck T, Nauck M, Sheng D, et al. Sitagliptin Study 024 Group. 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;64:562-76. doi:10.1111/j.1742-1241.2010. 02353.x.
49. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Sitagliptin Study 024 Group. 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;9:194-205. doi:10.1111/j.1463-1326.2006. 00704.x.
50. Merck. MK0431 (sitagliptin) and metformin co-Administration factorial study in patients with type 2 diabetes mellitus. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00103857.
51. 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;30:1979-87. doi:10.2337/dc07-0627.
52. Bristol-Myers Squibb. Saxagliptin treatment in subjects with type 2 diabetes who are not controlled with diet and exercise. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00121641.
53. Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R. CV181-011 Study Investigators. Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes. Curr Med Res Opin 2009;25:2401-11. doi:10.1185/03007990903178735.
54. Bristol-Myers Squibb. Study assessing saxagliptin treatment in type 2 diabetic subjects who are not controlled with metformin alone. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00121667.
55. DeFronzo RA, Hissa MN, Garber AJ, et al. Saxagliptin 014 Study Group. 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;32:1649-55. doi:10.2337/dc08-1984.
56. Takeda. Efficacy and safety of alogliptin combined with metformin in participants with type 2 diabetes mellitus. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00286442.
57. 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;63:46-55. doi:10.1111/j.1742-1241.2008.01933.x.
58. Takeda. Study of alogliptin combined with sulfonylurea in subjects with type 2 diabetes mellitus. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00286468.
59. 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;11:167-76. doi:10.1111/j.1463-1326.2008.01016.x.
60. Bristol-Myers Squibb. A study assessing saxagliptin treatment in type 2 diabetic subjects who are not controlled with TZD therapy alone. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00295633.
61. Hollander PL, Li J, Frederich R, Allen E, Chen R. CV181013 Investigators. Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus. Diab Vasc Dis Res 2011;8:125-35. doi:10.1177/1479164111404575.
62. 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;94:4810-9. doi:10.1210/jc.2009-0550.
63. Bristol-Myers Squibb. A phase 3 study of BMS-477118 in combination with metformin in subjects with type 2 diabetes who are not controlled with diet and exercise. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00327015.
64. Pfützner A, Paz-Pacheco E, Allen E, Frederich R, Chen R. CV181039 Investigators. Initial combination therapy with saxagliptin and metformin provides sustained glycaemic control and is well tolerated for up to 76 weeks. Diabetes Obes Metab 2011;13:567-76. doi:10.1111/j.1463-1326.2011.01385.x.
65. Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R. CV181-039 Investigators. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009;11:611-22. doi:10.1111/j.1463-1326.2009.01056.x.
66. Merck. Sitagliptin added-on to insulin study. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00395343.
67. Vilsbøll T, Rosenstock J, Yki-Järvinen H, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2010;12:167-77.
68. Merck. MK0431A comparative study in patients with type 2 diabetes. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00482729.
69. 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;13:644-52. doi:10.1111/j.1463-1326.2011.01390.x.
70. 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;13:841-9. doi:10.1111/j.1463-1326. 2011.01416.x.
71. AstraZeneca. Bristol-Myers Squibb. 52-week add-on to metformin comparison of saxagliptin and sulphonylurea, with a 52-week extension period. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00575588.
72. Göke B, Gallwitz B, Eriksson JG, Hellqvist A, Gause-Nilsson I. Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial. Int J Clin Pract 2013;67:307-16. doi:10.1111/ijcp.12119.
73. Göke B, Gallwitz B, Eriksson J, Hellqvist A, Gause-Nilsson I. D1680C00001 Investigators. Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. Int J Clin Pract 2010;64:1619-31. doi:10.1111/j.1742-1241.2010. 02510.x.
74. AstraZeneca. Treatment effect of saxagliptin compared with placebo in patients with type 2 diabetes and renal impairment. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00614939.
75. Nowicki M, Rychlik I, Haller H, et al. 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 2011;65:1230-9. doi:10.1111/j.1742-1241.2011.02812.x.
76. Nowicki M, Rychlik I, Haller H, Warren ML, Suchower L, Gause-Nilsson I. D1680C00007 Investigators. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab 2011;13:523-32. doi:10.1111/j.1463-1326.2011.01382.x.
77. Boehringer Ingelheim Pharmaceuticals. Efficacy and safety of BI 1356 in combination with metformin in patients with type 2 diabetes. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00622284.
78. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012;380:475-83. doi:10.1016/S0140-6736(12)60691-6.
79. Johnson & Johnson Pharmaceutical Research & Development. L.L.C. An efficacy, safety, and tolerability study of canagliflozin (JNJ-28431754) in patients with type 2 diabetes. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00642278.
80. Rosenstock J, Aggarwal N, Polidori D, et al. Canagliflozin DIA 2001 Study Group. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 2012;35:1232-8. doi:10.2337/dc11-1926.
81. Takeda. Efficacy and safety of alogliptin compared to glipizide in elderly diabetics. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00707993.
82. Rosenstock J, Wilson C, Fleck P. Alogliptin versus glipizide monotherapy in elderly type 2 diabetes mellitus patients with mild hyperglycaemia: a prospective, double-blind, randomized, 1-year study. Diabetes Obes Metab 2013;15:906-14. doi:10.1111/dom.12102.
83. Bristol-Myers Squibb. AstraZeneca. Safety and efficacy of saxagliptin plus insulin with or without metformin. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00757588.
84. Barnett AH, Charbonnel B, Donovan M, Fleming D, Chen R. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin 2012;28:513-23. doi:10.1185/03007995.2012.665046.
85. Boehringer Ingelheim Pharmaceuticals. Safety and efficacy of linagliptin (BI 1356) plus metformin in type 2 diabetes, factorial design. National Library of Medicine (US), 2000. https://clinicaltrials. gov/show/NCT00798161.
86. 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;14:565-74. doi:10.1111/j.1463-1326.2012.01590.x.
87. GlaxoSmithKline. Efficacy and safety of albiglutide in treatment of type 2 diabetes. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00838903.
88. Ahrén B, Johnson SL, Stewart M, et al. HARMONY 3 Study Group. HARMONY 3: 104-week randomized, double-blind, placebo-And active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care 2014;37:2141-8. doi:10.2337/dc14-0024.
89. Takeda. Efficacy and safety of alogliptin plus metformin compared to glipizide plus metformin in patients with type 2 diabetes mellitus (ENDURE). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00856284.
90. Del Prato S, Camisasca R, Wilson C, Fleck P. Durability of the efficacy and safety of alogliptin compared with glipizide in type 2 diabetes mellitus: a 2-year study. Diabetes Obes Metab 2014;16:1239-46. doi:10.1111/dom.12377.
91. Boehringer Ingelheim Pharmaceuticals; Eli Lilly and Company. Efficacy and safety of linagliptin in combination with insulin in patients with type 2 diabetes. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00954447.
92. AstraZeneca. Bristol-Myers Squibb. Saxagliptin compared to glimepiride in elderly type 2 diabetes patients, with inadequate glycemic control on metformin (GENERATION). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT01006603.
93. Merck. Safety and efficacy of sitagliptin compared with glimepiride in elderly participants with type 2 diabetes mellitus (MK-0431-251 AM2). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT01189890.
94. Takeda Pharmaceutical Company Limited. Efficacy and safety of alogliptin used in combination with ?-glucosidase inhibitor in participants with type 2 diabetes in Japan. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT01263483.
95. 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:10.1185/03 007995.2011.614936.
96. Ingelheim B; Eli Lilly and Company. Safety and efficacy of empagliflozin (BI 10773) and sitagliptin versus placebo over 76 weeks in patients with type 2 diabetes. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT01289990.
97. Pratley RE, Reusch JEB, 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;25:2361-71. doi:10.1185/03007990903156111.
98. Takeda. Study of alogliptin combined with pioglitazone in subjects with type 2 diabetes mellitus. National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00286494.
99. Pratley RE, Fleck P, Wilson C. Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab 2014;16:613-21. doi:10.1111/dom.12258.
100. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. Sitagliptin Study 019 Group. 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;28:1556-68. doi:10.1016/j.clinthera.2006.10.007.
101. Rosenstock J, Inzucchi SE, Seufert J, Fleck PR, Wilson CA, Mekki Q. Initial combination therapy with alogliptin and pioglitazone in drug-naïve patients with type 2 diabetes. Diabetes Care 2010;33:2406-8. doi:10.2337/dc10-0159.
102. 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;14:927-36. doi:10.1111/j.1463-1326.2012.01620.x.
103. Yang HK, Min KW, Park SW, et al. A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes. Endocr J 2015;62:449-62. doi:10.1507/endocrj.EJ14-0544.
104. Krum K, Lukashevich V, Bolli GB, Kozlovski P, Kothny W, Ponikowski P. No significant difference in risk of heart failure hospitalization with vildagliptin in diabetic patients with systolic chronic heart failure: VIVIDD Study. American Diabetes Association 74th Scientific Sessions (2014): 1028-P-2014. Presented on June 15, 2014.
105. Laakso M, Rosenstock J, Groop PH, et al. 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 2015;38:e15-7. doi:10.2337/dc14-1684.
106. AstraZeneca. Bristol-Myers Squibb. Does saxagliptin reduce the risk of cardiovascular events when used alone or added to other diabetes medications (SAVOR-TIMI 53). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT01107886.
107. Takeda. Cardiovascular outcomes study of alogliptin in patients with type 2 diabetes and acute coronary syndrome(EXAMINE). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT00968708.
108. White WB, Cannon CP, Heller SR, et al. EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327-35. doi:10.1056/NEJMoa1305889.
109. Gitt AK, Bramlage P, Binz C, Krekler M, Deeg E, Tschöpe D. Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting-results of the 1 year follow-up of the prospective DiaRegis registry. Int J Clin Pract 2013;67:1005-14. doi:10.1111/ijcp.12179.
110. Sharp M, Corp D. An Observational Study of Type II Diabetics Treated With Dual Therapy With or Without Sitagliptin (Januvia®/Xelevia®, MK-0431-201). National Library of Medicine (US), 2000. https://clinicaltrials.gov/show/NCT01357135.
111. Kannan S, Pantalone KM, Matsuda S, Wells BJ, Karafa M, Zimmerman RS. Risk of overall mortality and cardiovascular events in patients with type 2 diabetes on dual drug therapy including metformin: A large database study from the Cleveland Clinic. J Diabetes 2015; [Epub ahead of print]. doi:10.1111/1753-0407.12301.
112. Eurich DT, Weir DL, Simpson SH, Senthilselvan A, McAlister FA. Risk of new onset heart failure in patients using sitagliptin. American Diabetes Association 74th Scientific Sessions (2014): 135-LB-2014. Presented on 15 June, 2014.
113. Seong JM, Choi NK, Shin JY, et al. Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study. PLoS One 2015;10:e0124287. doi:10.1371/journal.pone.0124287.
114. Suh S, Seo GH, Jung CH, et al. Increased risk of hospitalization for heart failure with newly prescribed dipeptidyl peptidase-4 inhibitors and pioglitazone using the Korean health insurance claims database. Diabetes Metab J 2015;39:247-52. doi:10.4093/dmj.2015.39.3.247.
115. Velez M, Peterson EL, Wells K, et al. Association of antidiabetic medications targeting the glucagon-like peptide 1 pathway and heart failure events in patients with diabetes. J Card Fail 2015;21:2-8. doi:10.1016/j.cardfail.2014.10.012.
116. Chen DY, Wang SH, Mao CT, et al. Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: A nationwide cohort study. Int J Cardiol 2015;181:200-6. doi:10.1016/j.ijcard.2014.12.029.
117. Wu S, Hopper I, Skiba M, Krum H. Dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes: meta-Analysis of randomized clinical trials with 55,141 participants. Cardiovasc Ther 2014;32:147-58. doi:10.1111/1755-5922.12075.
118. Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-Analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 2014;24:689-97. doi:10.1016/j. numecd.2014.01.017.
119. Clifton P. Do dipeptidyl peptidase IV (DPP-IV) inhibitors cause heart failureClin Ther 2014;36:2072-9. doi:10.1016/j.clinthera.2014. 10.009.