A review of dipeptidyl peptidase-4 inhibitors. Hot topics from randomized controlled trials

Diabetes, Obesity and Metabolism

Volumn 20, Issue , 2018, Pages 34-46

  Deacon, Carolyn F ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

dipeptidyl peptidase 4; incretin therapy; type 2 diabetes

Indexed keywords

ACARBOSE; ALBIGLUTIDE; ALOGLIPTIN; CANAGLIFLOZIN; DAPAGLIFLOZIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; DULAGLUTIDE; EMPAGLIFLOZIN; EXENDIN 4; GLIBENCLAMIDE; GLICLAZIDE; GLIMEPIRIDE; GLIPIZIDE; INSULIN; LINAGLIPTIN; LIRAGLUTIDE; LIXISENATIDE; METFORMIN; MIGLITOL; NATEGLINIDE; PIOGLITAZONE; REPAGLINIDE; ROSIGLITAZONE; SAXAGLIPTIN; SEMAGLUTIDE; SITAGLIPTIN; VILDAGLIPTIN; VOGLIBOSE; ANTIDIABETIC AGENT; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN;

CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC KIDNEY FAILURE; CLINICAL EFFECTIVENESS; DIABETIC NEPHROPATHY; DISEASE SEVERITY; DOSE RESPONSE; DRUG DOSE INCREASE; DRUG DOSE INTENSIFICATION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG RESEARCH; DRUG SAFETY; DRUG TOLERABILITY; FATTY LIVER; GLYCEMIC CONTROL; HEART FAILURE; HIGH RISK POPULATION; HOSPITAL MANAGEMENT; HUMAN; HYPERGLYCEMIA; KIDNEY DYSFUNCTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENAL PROTECTION; REVIEW; TREATMENT PLANNING; BLOOD; CHEMICALLY INDUCED; DRUG EFFECT; GLUCOSE BLOOD LEVEL; HYPOGLYCEMIA; TREATMENT OUTCOME;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; GLYCATED HEMOGLOBIN A; HUMANS; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TREATMENT OUTCOME;

EID: 85041084254     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.13135     Document Type: Review

References (112)

1. Andersen ES, Deacon CF, Holst JJ. Do we know the true mechanism of action of the DPP-4 inhibitors? Diabetes Obes Metab. 2017; May 24: https://doi.org/10.1111/dom.13018. [Epub ahead of print].
2. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995;44:1126–1131.
3. Ahrén B, Simonsson E, Larsson H, et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care. 2002;25:869–875.
4. Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011;13:7–18.
5. Deacon CF, Lebovitz HE. Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas. Diabetes Obes Metab. 2016;18:333–347.
6. Davidson JA. The placement of DPP-4 inhibitors in clinical practice recommendations for the treatment of type 2 diabetes. Endocr Pract. 2013;19:1050–1061.
7. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58:429–442.
8. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management alogorithm—2016 executive summary. Endocr Pract. 2016;22:84–113.
9. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–1326.
10. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–1335.
11. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–242.
12. Marx N, Rosenstock J, Kahn SE, et al. Design and baseline characteristics of the CARdiovascular outcome trial of LINAgliptin versus glimepiride in type 2 diabetes (CAROLINA®). Diab Vasc Dis Res. 2015;12:164–174.
13. Perkovic V, Rosenstock J, Alexander JH, et al. CARMELINA® trial baseline characteristics: a cardiovascular and renal microvascular outcome trial with linagliptin in patients with type 2 diabetes at high vascular risk: Poster presented: 53rd Annual Meeting of the EASD, 2017; Lisbon, Poster 779. https://www.easd.org/virtualmeeting/home.html. Accessed September 19, 2017.
14. 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;15:112–120.
15. Deacon CF, Marx N. Potential cardiovascular effects of incretin-based therapies. Expert Rev Cardiovasc Ther. 2012;10:337–351.
16. Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114:1788–1803.
17. Read PA, Khan FZ, Heck PM, Hoole SP, Dutka DP. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging. 2010;3:195–201.
18. McCormick LM, Kydd AC, Read PA, et al. Chronic dipeptidyl peptidase-4 inhibition with sitagliptin is associated with sustained protection against ischemic left ventricular dysfunction in a pilot study of patients with type 2 diabetes mellitus and coronary artery disease. Circ Cardiovasc Imaging. 2014;7:274–281.
19. Kato S, Fukui K, Kirigaya H, et al. Inhibition of DPP-4 by alogliptin improves coronary flow reserve and left ventricular systolic function evaluated by phase contrast cine magnetic resonance imaging in patients with type 2 diabetes and coronary artery disease. Int J Cardiol. 2016;223:770–775.
20. Yamada H, Tanaka A, Kusunose K, et al. Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study. Cardiovasc Diabetol. 2017;16:63.
21. Engel SS, Golm GT, Shapiro D, Davies MJ, Kaufman KD, Goldstein BJ. Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis. Cardiovasc Diabetol. 2013;12:3.
22. White WB, Pratley R, Fleck P, et al. Cardiovascular safety of the dipeptidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus. Diabetes Obes Metab. 2013;15:668–673.
23. Iqbal N, Parker A, Frederich R, Donovan M, Hirshberg B. Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials. Cardiovasc Diabetol. 2014;13:33.
24. McInnes G, Evans M, Del Prato S, et al. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17,000 patients. Diabetes Obes Metab. 2015;17:1085–1092.
25. Rosenstock J, Marx N, Neubacher D, et al. Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. 2015;14:57.
26. Barbieri M, Rizzo MR, Marfella R, et al. Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors. Atherosclerosis. 2013;227:349–354.
27. Mita T, Katakami N, Shiraiwa T, et al. Sitagliptin attenuates the progression of carotid intima-media thickening in insulin-treated patients with type 2 diabetes: the sitagliptin preventive study of intima-media thickness evaluation (SPIKE): a randomized controlled trial. Diabetes Care. 2016;39:455–464.
28. Mita T, Katakami N, Yoshii H, et al. Alogliptin, a dipeptidyl peptidase 4 inhibitor, prevents the progression of carotid atherosclerosis in patients with type 2 diabetes: the study of preventive effects of alogliptin on diabetic atherosclerosis (SPEAD-A). Diabetes Care. 2016;39:139–148.
29. Oyama J, Murohara T, Kitakaze M, et al. The effect of sitagliptin on carotid artery atherosclerosis in type 2 diabetes: the PROLOGUE randomized controlled trial. PLoS Med. 2016;13:e1002051.
30. de Boer SA, Heerspink HJL, Juárez Orozco LE, et al. Effect of linagliptin on pulse wave velocity in early type 2 diabetes: a randomized, double-blind, controlled 26-week trial (RELEASE). Diabetes Obes Metab. 2017;19:1147–1154.
31. 18F-fluorodeoxyglucose positron emission tomography uptake: a randomized controlled trial (RELEASE). J Am Coll Cardiol. 2017;69:1097–1098.
32. Iglay K, Hannachi H, Joseph Howie P, et al. Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus. Curr Med Res Opin. 2016;32:1243–1252.
33. Gross L, Theiss HD, Grabmaier U, et al. Combined therapy with sitagliptin plus granulocyte-colony stimulating factor in patients with acute myocardial infarction—long-term results of the SITAGRAMI trial. Int J Cardiol. 2016;215:441–445.
34. Scirica BM, Braunwald E, Raz I, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579–1588.
35. Zannad F, Cannon CP, Cushman WC, et al. 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;385:2067–2076.
36. McGuire DK, Van de Werf F, Armstrong PW, et al. Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: secondary analysis of a randomized clinical trial. JAMA Cardiol. 2016;1:126–135.
37. Filion KB, Azoulay L, Platt RW, et al. A multicenter observational study of incretin-based drugs and heart failure. N Engl J Med. 2016;374:1145–1154.
38. OH Y, Filion KB, Azoulay L, Patenaude V, Majdan A, Suissa S. Incretin-based drugs and the risk of congestive heart failure. Diabetes Care. 2015;38:277–284.
39. Koyani CN, Kolesnik E, Woelkart G, et al. Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure. Biochem Pharmacol. 2017;145:64–80.
40. 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;36:1067–1073.
41. Kothny W, Lukashevich V, Foley JE, Rendell MS, Schweizer A. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial. Diabetologia. 2015;58:2020–2026.
42. Kothny W, Shao Q, Groop PH, Lukashevich V. One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab. 2012;14:1032–1039.
43. 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;65:1230–1239.
44. McGill JB, Sloan L, Newman J, et al. 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. 2013;36:237–244.
45. 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;61:579–587.
46. Ito M, Abe M, Okada K, et al. The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis. Endocr J. 2011;58:979–987.
47. Abe M, Higuchi T, Moriuchi M, et al. Efficacy and safety of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in hemodialysis patients with diabetic nephropathy: a randomized open-label prospective trial. Diabetes Res Clin Pract. 2016;116:244–252.
48. Udell JA, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: observations from the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38:696–705.
49. Cornel JH, Bakris GL, Stevens SR, et al. Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2 diabetes: outcomes from TECOS. Diabetes Care. 2016;39:2304–2310.
50. Engel SS, Suryawanshi S, Stevens SR, et al. Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS. Diabetes Obes Metab. 2017;19:1587–1593.
51. Mosenzon O, Leibowitz G, Bhatt DL, et al. Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial. Diabetes Care. 2017;40:69–76.
52. Muskiet MH, Tonneijck L, Smits MM, Kramer MH, Heerspink HJ, van Raalte DH. Pleiotropic effects of type 2 diabetes management strategies on renal risk factors. Lancet Diabetes Endocrinol. 2015;3:367–381.
53. Rieg T, Gerasimova M, Murray F, et al. Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. Am J Physiol Renal Physiol. 2012;303:F963–F971.
54. Moroi M, Kubota T. Diuretic and natriuretic effects of dipeptidyl peptidase-4 inhibitor teneligliptin: the contribution of glucagon-like peptide-1. J Cardiovasc Pharmacol. 2015;66:159–164.
55. Takashima S, Fujita H, Fujishima H, et al. Stromal cell-derived factor-1 is upregulated by dipeptidyl peptidase-4 inhibition and has protective roles in progressive diabetic nephropathy. Kidney Int. 2016;90:783–796.
56. Liu WJ, Xie SH, Liu YN, et al. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther. 2012;340:248–255.
57. Sharkovska Y, Reichetzeder C, Alter M, et al. Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy. J Hypertens. 2014;32:2211–2223.
58. Mega C, de Lemos ET, Vala H, et al. Diabetic nephropathy amelioration by a low-dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat). Exp Diabetes Res. 2011;2011:162092.
59. Jung E, Kim J, Ho Kim S, Kim S, Cho MH. Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy. Eur J Pharmacol. 2015;761:116–124.
60. Tonneijck L, Smits MM, Muskiet MH, et al. Renal effects of DPP-4 inhibitor sitagliptin or GLP-1 receptor agonist liraglutide in overweight patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2016;39:2042–2050.
61. Ott C, Kistner I, Keller M, et al. Effects of linagliptin on renal endothelial function in patients with type 2 diabetes: a randomised clinical trial. Diabetologia. 2016;59:2579–2587.
62. Groop PH, Cooper ME, Perkovic V, et al. Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA-T2D trial. Diabetes Obes Metab. 2017; 19:1610–1619.
63. Lovshin JA, Rajasekeran H, Lytvyn Y, et al. Dipeptidyl peptidase 4 inhibition stimulates distal tubular natriuresis and increases in circulating SDF-1α1-67 in patients with type 2 diabetes. Diabetes Care. 2017;40:1073–1081.
64. Yoon SA, Han BG, Kim SG, et al. Efficacy, safety and albuminuria-reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: a 12-week, double-blind randomized study (the GUARD study). Diabetes Obes Metab. 2017;19:590–598.
65. Cooper ME, Perkovic V, McGill JB, et al. Kidney disease end points in a pooled analysis of individual patient-level data from a large clinical trials program of the dipeptidyl peptidase 4 inhibitor linagliptin in type 2 diabetes. Am J Kidney Dis. 2015;66:441–449.
66. Mori H, Okada Y, Arao T, Tanaka Y. Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus. J Diabetes Invest. 2014;5:313–319.
67. Goldshtein I, Karasik A, Melzer-Cohen C, et al. Urinary albumin excretion with sitagliptin compared to sulfonylurea as add on to metformin in type 2 diabetes patients with albuminuria: a real-world evidence study. J Diabetes Complications. 2016;30:1354–1359.
68. Sakata K, Hayakawa M, Yano Y, et al. Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE) - receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes. Diabetes Metab Res Rev. 2013;29:624–630.
69. Tani S, Nagao K, Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study. Am J Cardiovasc Drugs. 2013;13:443–450.
70. Ahren B, Schweizer A, Dejager S, et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab. 2009;94:1236–1243.
71. Farngren J, Persson M, Schweizer A, Foley JE, Ahrén B. Glucagon dynamics during hypoglycaemia and food-re-challenge following treatment with vildagliptin in insulin-treated patients with type 2 diabetes. Diabetes Obes Metab. 2014;16:812–818.
72. Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia. 2007;50:1148–1155.
73. Rosenstock J, Rendell MS, Gross JL, Fleck PR, Wilson CA, Mekki Q. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab. 2009;11:1145–1152.
74. 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;12:167–177.
75. 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;28:513–523.
76. Kaku K, Mori M, Kanoo T, Katou M, Seino Y. Efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes: a randomized, double-blind, 12-week, placebo-controlled trial followed by an open-label, long-term extension phase. Expert Opin Pharmacother. 2014;15:2121–2130.
77. Sato S, Saisho Y, Kou K, et al. Efficacy and safety of sitagliptin added to insulin in Japanese patients with type 2 diabetes: the EDIT randomized trial. PLoS One. 2015;10:e0121988.
78. Durán-Garcia S, Lee J, Yki-Järvinen H, et al. Efficacy and safety of linagliptin as add-on therapy to basal insulin and metformin in people with type 2 diabetes. Diabet Med. 2016;33:926–933.
79. Tura A, Farngren J, Schweizer A, Foley JE, Pacini G, Ahrén B. Four-point preprandial self-monitoring of blood glucose for the assessment of glycemic control and variability in patients with type 2 diabetes treated with insulin and vildagliptin. Int J Endocrinol. 2015;2015:484231.
80. Li FF, Jiang LL, Yan RN, et al. Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes: a randomized, control, open-labeled trial. Medicine (Baltimore). 2016;95:e5229.
81. Li FF, Shen Y, Sun R, et al. Effects of vildagliptin add-on insulin therapy on nocturnal glycemic variations in uncontrolled type 2 diabetes. Diabetes Ther. 2017;8:1111–1122.
82. Barnett AH, Charbonnel B, Li J, Donovan M, Fleming D, Iqbal N. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy. Clin Drug Investig. 2013;33:707–717.
83. Kanazawa I, Tanaka KI, Notsu M, et al. Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment. Diabetes Res Clin Pract. 2017;123:9–17.
84. Kadowaki T, Kondo K, Sasaki N, et al. Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period. Expert Opin Pharmacother. 2017;18:1291–1300.
85. Kadowaki T, Muto S, Ouchi Y, Shimazaki R, Seino Y. Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension. Expert Opin Pharmacother. 2017; Sep 13, https://doi.org/10.1080/14656566.2017.1379990. [Epub ahead of print].
86. Inzucchi SE, Nauck MA, Hehnke U, Woerle HJ, von Eynatten M, Henry RR. Improved glucose control with reduced hypoglycaemic risk when linagliptin is added to basal insulin in elderly patients with type 2 diabetes. Diabetes Obes Metab. 2015;17:868–877.
87. Lukashevich V, Schweizer A, Foley JE, Dickinson S, Groop PH, Kothny W. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment. Vasc Health Risk Manag. 2013;9:21–28.
88. McGill JB, Yki-Järvinen H, Crowe S, Woerle HJ, von Eynatten M. Combination of the dipeptidyl peptidase-4 inhibitor linagliptin with insulin-based regimens in type 2 diabetes and chronic kidney disease. Diab Vasc Dis Res. 2015;12:249–257.
89. Hong ES, Khang AR, Yoon JW, et al. Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study. Diabetes Obes Metab. 2012;14:795–802.
90. Canadian Agency for Drugs and Technologies in Health. Combination use of insulin and incretins in type 2 diabetes. CADTH Optimal Use Report; vol.3, no. 1c. Ottawa: The Agency; 2013,
91. Mathieu C, Shankar RR, Lorber D, et al. A randomized clinical trial to evaluate the efficacy and safety of co-administration of sitagliptin with intensively titrated insulin glargine. Diabetes Ther. 2015;6:127–142.
92. Linjawi S, Sothiratnam R, Sari R, Andersen H, Hiort LC, Rao P. The study of once- and twice-daily biphasic insulin aspart 30 (BIAsp 30) with sitagliptin, and twice-daily BIAsp 30 without sitagliptin, in patients with type 2 diabetes uncontrolled on sitagliptin and metformin-the Sit2Mix trial. Prim Care Diabetes. 2015;9:370–376.
93. Cao Y, Gao F, Zhang Q, et al. Efficacy and safety of coadministration of sitagliptin with insulin glargine in type 2 diabetes. J Diabetes. 2017;9:502–509.
94. Hollander P, Raslova K, Skjøth TV, Råstam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab. 2011;13:268–275.
95. Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:16–38.
96. Umpierrez GE, Gianchandani R, Smiley D, et al. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013;36:3430–3435.
97. Pasquel FJ, Gianchandani R, Rubin DJ, et al. Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol. 2017;5:125–133.
98. Garg R, Schuman B, Hurwitz S, Metzger C, Bhandari S. Safety and efficacy of saxagliptin for glycemic control in non-critically ill hospitalized patients. BMJ Open Diabetes Res Care. 2017;5:e000394.
99. Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13:2062–2070.
100. Nakouti T, Karagiannis AK, Tziomalos K, Cholongitas E. Incretin-based antidiabetic agents for the management of non-alcoholic fatty liver disease. Curr Vasc Pharmacol. 2015;13:649–657.
101. Smits MM, Tonneijck L, Muskiet MH, et al. Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial. Diabetologia. 2016;59:2588–2593.
102. Cui J, Philo L, Nguyen P, et al. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol. 2016;65:369–376.
103. Joy TR, McKenzie CA, Tirona RG, et al. Sitagliptin in patients with non-alcoholic steatohepatitis: a randomized, placebo-controlled trial. World J Gastroenterol. 2017;23:141–150.
104. Macauley M, Hollingsworth KG, Smith FE, et al. Effect of vildagliptin on hepatic steatosis. Clin Endocrinol Metab. 2015;100:1578–1585.
105. Kato H, Nagai Y, Ohta A, et al. Effect of sitagliptin on intrahepatic lipid content and body fat in patients with type 2 diabetes. Diabetes Res Clin Pract. 2015;109:199–205.
106. Hussain M, Majeed Babar MZ, Hussain MS, Akhtar L. Vildagliptin ameliorates biochemical, metabolic and fatty changes associated with non alcoholic fatty liver disease. Pak J Med Sci. 2016;32:1396–1401.
107. Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382:1413–1423.
108. Leiter LA, Teoh H, Braunwald E, et al. Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38:1145–1153.
109. Bethel MA, Engel SS, Green JB, et al. Assessing the safety of sitagliptin in older participants in the trial evaluating cardiovascular outcomes with sitagliptin (TECOS). Diabetes Care. 2017;40:494–501.
110. Awata T, Shimada A, Maruyama T, et al. Possible long-term efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, for slowly progressive type 1 diabetes (SPIDDM) in the stage of non-insulin-dependency: an open-label randomized controlled pilot trial (SPAN-S). Diabetes Ther. 2017;8:1123–1134.
111. Lynch M, Ahern TB, Timoney I, et al. Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial. Trials. 2016;17:29.
112. Elkind-Hirsch KE, Paterson MS, Seidemann EL, Gutowski HC. Short-term therapy with combination dipeptidyl peptidase-4 inhibitor saxagliptin/metformin extended release (XR) is superior to saxagliptin or metformin XR monotherapy in prediabetic women with polycystic ovary syndrome: a single-blind, randomized, pilot study. Fertil Steril. 2017;107:253–260.