Bonus Effects of Antidiabetic Drugs: Possible Beneficial Effects on Endothelial Dysfunction, Vascular Inflammation and Atherosclerosis

Basic and Clinical Pharmacology and Toxicology

Volumn 123, Issue 5, 2018, Pages 523-538

  Pereira, Camila A ^a   Carneiro, Fernando S ^a   Matsumoto, Takayuki ^b   Tostes, Rita C ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b HOSHI UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; GLUCOSE; MATRIX METALLOPROTEINASE;

APOPTOSIS; ATHEROSCLEROSIS; BODY WEIGHT CONTROL; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CELL MIGRATION; DIABETES MELLITUS; DISEASE ASSOCIATION; DRUG EFFECT; ENDOTHELIAL DYSFUNCTION; ENZYME ACTIVITY; GENE EXPRESSION; GENETIC ASSOCIATION; GLUCOSE LEVEL; HOMEOSTASIS; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERLIPIDEMIA; IMMUNOCOMPETENT CELL; LIFE EXPECTANCY; LIFESTYLE MODIFICATION; MORTALITY RISK; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; VASCULITIS; CARDIOVASCULAR DISEASE; DIABETIC ANGIOPATHY; IMMUNOLOGY; INFLAMMATION; METABOLISM; TREATMENT OUTCOME; VASCULAR RESISTANCE;

CARDIOVASCULAR DISEASES; DIABETIC ANGIOPATHIES; HUMANS; HYPOGLYCEMIC AGENTS; INFLAMMATION; OXIDATIVE STRESS; TREATMENT OUTCOME; VASCULAR RESISTANCE;

EID: 85050873934     PISSN: 17427835     EISSN: 17427843     Source Type: Journal    
DOI: 10.1111/bcpt.13054     Document Type: Review

References (127)

1. IDF Diabetes Atlas, 8th edn. International Diabetes Federation, 2017. www.diabetesatlas.org (last accessed on 27 May 2018)
2. ADA. American Diabetes Association – Standards of medical care in diabetes. Diabetes Care 2015;38(Suppl 1):S1–93
3. Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR et al. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 2003;46:760–5
4. Sharma NK, Archer DB, Hadden DR, Merrett JD, Maguire CJ. Morbidity and mortality in patients with diabetic retinopathy. Trans Ophthalmol Soc UK 1980;100:83–9
5. Bertoni AG, Krop JS, Anderson GF, Brancati FL. Diabetes-related morbidity and mortality in a national sample of U.S. elders. Diabetes Care 2002;25:471–5
6. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009;53:S35–42
7. Folli F, Corradi D, Fanti P, Davalli A, Paez A, Giaccari A et al. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and macrovascular complications: avenues for a mechanistic-based therapeutic approach. Curr Diabetes Rev 2011;7:313–24
8. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010;107:1058–70
9. Park JB, Charbonneau F, Schiffrin EL. Correlation of endothelial function in large and small arteries in human essential hypertension. J Hypertens 2001;19:415–20
10. Monnink SH, van Haelst PL, van Boven AJ, Stroes ES, Tio RA, Plokker TW et al. Endothelial dysfunction in patients with coronary artery disease: a comparison of three frequently reported tests. J Investig Med 2002;50:19–24
11. Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C et al. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 2002;106:3073–8
12. Bolton CH, Downs LG, Victory JG, Dwight JF, Tomson CR, Mackness MI et al. Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines. Nephrol Dial Transplant 2001;16:1189–97
13. Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A. The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol 2003;42:1037–43
14. Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Keaney JF Jr, Creager MA. Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 2003;285:H2392–8
15. Rizzoni D, Porteri E, Guelfi D, Muiesan ML, Valentini U, Cimino A et al. Structural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus. Circulation 2001;103:1238–44
16. Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation 2004;109:1750–5
17. Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 1996;94:1298–303
18. DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988;37:667–87
19. Cersosimo E, DeFronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 2006;22:423–36
20. Hunt JV, Dean RT, Wolff SP. Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J 1988;256:205–12
21. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787–90
22. James AM, Murphy MP. How mitochondrial damage affects cell function. J Biomed Sci 2002;9:475–87
23. Jiang BH, Zheng JZ, Aoki M, Vogt PK. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci USA 2000;97:1749–53
24. Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 2000;101:676–81
25. Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 1999;103:253–9
26. Steinberg HO, Paradisi G, Hook G, Crowder K, Cronin J, Baron AD. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 2000;49:1231–8
27. Matsumoto T, Kobayashi T, Kamata K. Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats. Am J Physiol Heart Circ Physiol 2003;285:H283–91
28. Coleman HA, Tare M, Parkington HC. Nonlinear effects of potassium channel blockers on endothelium-dependent hyperpolarization. Acta Physiol (Oxf) 2017;219:324–34
29. Feletou M, Vanhoutte PM. EDHF: new therapeutic targets? Pharmacol Res 2004;49:565–80
30. Feletou M. Endothelium-dependent hyperpolarization and endothelial dysfunction. J Cardiovasc Pharmacol 2016;67:373–87
31. Garland CJ, Dora KA. EDH: endothelium-dependent hyperpolarization and microvascular signalling. Acta Physiol (Oxf) 2017;219:152–61
32. Leung SW, Vanhoutte PM. Endothelium-dependent hyperpolarization: age, gender and blood pressure, do they matter? Acta Physiol (Oxf) 2017;219:108–23
33. Matsumoto T, Wakabayashi K, Kobayashi T, Kamata K. Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats. Am J Physiol Heart Circ Physiol 2005;289:H2234–43
34. Matsumoto T, Wakabayashi K, Kobayashi T, Kamata K. Diabetes-related changes in cAMP-dependent protein kinase activity and decrease in relaxation response in rat mesenteric artery. Am J Physiol Heart Circ Physiol 2004;287:H1064–71
35. Matsumoto T, Miyamori K, Kobayashi T, Kamata K. Specific impairment of endothelium-derived hyperpolarizing factor-type relaxation in mesenteric arteries from streptozotocin-induced diabetic mice. Vascul Pharmacol 2006;44:450–60
36. Nakazawa T, Kaneko Y, Mori A, Saito M, Sakamoto K, Nakahara T et al. Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats. Vascul Pharmacol 2007;46:153–9
37. Kamata K, Ohuchi K, Kirisawa H. Altered endothelium-dependent and -independent hyperpolarization and endothelium-dependent relaxation in carotid arteries isolated from streptozotocin-induced diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 2000;362:52–9
38. Shen B, Ye CL, Ye KH, Liu JJ. Mechanism underlying enhanced endothelium-dependent vasodilatation in thoracic aorta of early stage streptozotocin-induced diabetic mice. Acta Pharmacol Sin 2003;24:422–8
39. Malakul W, Thirawarapan S, Suvitayavat W, Woodman OL. Type 1 diabetes and hypercholesterolaemia reveal the contribution of endothelium-derived hyperpolarizing factor to endothelium-dependent relaxation of the rat aorta. Clin Exp Pharmacol Physiol 2008;35:192–200
40. Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res 2010;106:1319–31
41. Matsumoto T, Lopes RA, Taguchi K, Kobayashi T, Tostes RC. Linking the beneficial effects of current therapeutic approaches in diabetes to the vascular endothelin system. Life Sci 2014;118:129–35
42. Cosentino F, Hishikawa K, Katusic ZS, Luscher TF. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 1997;96:25–8
43. Matsumoto T, Noguchi E, Kobayashi T, Kamata K. Mechanisms underlying the chronic pioglitazone treatment-induced improvement in the impaired endothelium-dependent relaxation seen in aortas from diabetic rats. Free Radic Biol Med 2007;42:993–1007
44. Matsumoto T, Noguchi E, Ishida K, Kobayashi T, Yamada N, Kamata K. Metformin normalizes endothelial function by suppressing vasoconstrictor prostanoids in mesenteric arteries from OLETF rats, a model of type 2 diabetes. Am J Physiol Heart Circ Physiol 2008;295:H1165–76
45. Matsumoto T, Nakayama N, Ishida K, Kobayashi T, Kamata K. Eicosapentaenoic acid improves imbalance between vasodilator and vasoconstrictor actions of endothelium-derived factors in mesenteric arteries from rats at chronic stage of type 2 diabetes. J Pharmacol Exp Ther 2009;329:324–34
46. Matsumoto T, Watanabe S, Kawamura R, Taguchi K, Kobayashi T. Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis. Pflugers Arch 2014;466:331–42
47. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 2001;88:E14–22
48. Matsumoto T, Goulopoulou S, Taguchi K, Tostes RC, Kobayashi T. Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes. Br J Pharmacol 2015;172:3980–4001
49. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988;318:1315–21
50. Fulop N, Marchase RB, Chatham JC. Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system. Cardiovasc Res 2007;73:288–97
51. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 2013;13:709–21
52. Spitaler MM, Graier WF. Vascular targets of redox signalling in diabetes mellitus. Diabetologia 2002;45:476–94
53. Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med 2012;2012:918267
54. Zhu J, Krishnegowda G, Gowda DC. Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: the requirement of extracellular signal-regulated kinase, p38, c-Jun N-terminal kinase and NF-kappaB pathways for the expression of proinflammatory cytokines and nitric oxide. J Biol Chem 2005;280:8617–27
55. Pawate S, Bhat NR. C-Jun N-terminal kinase (JNK) regulation of iNOS expression in glial cells: predominant role of JNK1 isoform. Antioxid Redox Signal 2006;8:903–9
56. Quinn BJ, Kitagawa H, Memmott RM, Gills JJ, Dennis PA. Repositioning metformin for cancer prevention and treatment. Trends Endocrinol Metab 2013;24:469–80
57. Sena CM, Matafome P, Louro T, Nunes E, Fernandes R, Seica RM. Metformin restores endothelial function in aorta of diabetic rats. Br J Pharmacol 2011;163:424–37
58. Wang Q, Zhang M, Torres G, Wu S, Ouyang C, Xie Z et al. Metformin suppresses diabetes-accelerated atherosclerosis via the inhibition of Drp1-mediated mitochondrial fission. Diabetes 2017;66:193–205
59. Lu J, Ji J, Meng H, Wang D, Jiang B, Liu L et al. The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats. Cardiovasc Diabetol 2013;12:58
60. Zhou Z, Tang Y, Jin X, Chen C, Lu Y, Liu L et al. Metformin inhibits advanced glycation end products-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFkappaB pathway suppression. J Diabetes Res 2016;2016:4847812
61. Isoda K, Young JL, Zirlik A, MacFarlane LA, Tsuboi N, Gerdes N et al. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol 2006;26:611–7
62. Caballero AE, Delgado A, Aguilar-Salinas CA, Herrera AN, Castillo JL, Cabrera T et al. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 2004;89:3943–8
63. Lund SS, Tarnow L, Stehouwer CD, Schalkwijk CG, Teerlink T, Gram J et al. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Eur J Endocrinol 2008;158:631–41
64. Xu W, Deng YY, Yang L, Zhao S, Liu J, Zhao Z et al. Metformin ameliorates the proinflammatory state in patients with carotid artery atherosclerosis through sirtuin 1 induction. Transl Res 2015;166:451–8
65. Dehkordi EH, Sattari F, Khoshdel A, Kasiri K. Effect of folic acid and metformin on insulin resistance and inflammatory factors of obese children and adolescents. J Res Med Sci 2016;21:71
66. Victor VM, Rovira-Llopis S, Banuls C, Diaz-Morales N, Lopez-Domenech S, Escribano-Lopez I et al. Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients. Atherosclerosis 2015;242:167–73
67. Goldberg RB, Aroda VR, Bluemke DA, Barrett-Connor E, Budoff M, Crandall JP et al. Effect of long-term metformin and lifestyle in the diabetes prevention program and its outcome study on coronary artery calcium. Circulation 2017;136:52–64
68. Kalra S, Aamir AH, Raza A, Das AK, Azad Khan AK, Shrestha D et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: a consensus statement. Indian J Endocrinol Metab 2015;19:577–96
69. Kim HW, Li H, Kim HS, Shin SE, Jung WK, Ha KS et al. The anti-diabetic drug repaglinide induces vasorelaxation via activation of PKA and PKG in aortic smooth muscle. Vascul Pharmacol 2016;84:38–46
70. Chukwunonso Obi B, Chinwuba Okoye T, Okpashi VE, Nonye Igwe C, Olisah Alumanah E. Comparative study of the antioxidant effects of metformin, glibenclamide, and repaglinide in alloxan-induced diabetic rats. J Diabetes Res 2016;2016:1635361
71. Renier G, Desfaits AC, Serri O. Effect of gliclazide on monocyte-endothelium interactions in diabetes. J Diabetes Complications 2000;14:215–23
72. Schmoelzer I, Wascher TC. Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance. Cardiovasc Diabetol 2006;5:9
73. Gallagher EJ, LeRoith D. Obesity and diabetes: the increased risk of cancer and cancer-related mortality. Physiol Rev 2015;95:727–48
74. Kong X, Ma MZ, Qin L, Zhang Y, Li XY, Wang GD et al. Pioglitazone enhances the blood pressure-lowering effect of losartan via synergistic attenuation of angiotensin II-induced vasoconstriction. J Renin Angiotensin Aldosterone Syst 2014;15:259–70
75. Aliperti LA, Lasker GF, Hagan SS, Hellstrom JA, Gokce A, Trost LW et al. Efficacy of pioglitazone on erectile function recovery in a rat model of cavernous nerve injury. Urology 2014;84:1122–7
76. Gumieniczek A, Komsta L, Chehab MR. Effects of two oral antidiabetics, pioglitazone and repaglinide, on aconitase inactivation, inflammation and oxidative/nitrosative stress in tissues under alloxan-induced hyperglycemia. Eur J Pharmacol 2011;659:89–93
77. Behringer A, Trappiel M, Berghausen EM, Ten Freyhaus H, Wellnhofer E, Odenthal M et al. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension. Naunyn Schmiedebergs Arch Pharmacol 2016;389:369–79
78. Rudnicki M, Tripodi GL, Ferrer R, Bosca L, Pitta MG, Pitta IR et al. New thiazolidinediones affect endothelial cell activation and angiogenesis. Eur J Pharmacol 2016;782:98–106
79. Fidan E, Onder Ersoz H, Yilmaz M, Yilmaz H, Kocak M, Karahan C et al. The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus. Acta Diabetol 2011;48:297–302
80. Stocker DJ, Taylor AJ, Langley RW, Jezior MR, Vigersky RA. A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes. Am Heart J 2007;153:445.e1-6
81. Stojanovic M, Prostran M, Radenkovic M. Thiazolidinediones improve flow-mediated dilation: a meta-analysis of randomized clinical trials. Eur J Clin Pharmacol 2016;72:385–98
82. Saremi A, Schwenke DC, Buchanan TA, Hodis HN, Mack WJ, Banerji M et al. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol 2013;33:393–9
83. Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 2007;113:546–93
84. McDougall C, McKay GA et al. Drugs for diabetes: part 5 DPP-4 inhibitors. Br J Cardiol 2011;18:130–2
85. Li PC, Liu LF, Jou MJ, Wang HK. The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice. BMC Neurosci 2016;17:37
86. Kuroki T, Tanaka R, Shimada Y, Yamashiro K, Ueno Y, Shimura H et al. Exendin-4 inhibits matrix metalloproteinase-9 activation and reduces infarct growth after focal cerebral ischemia in hyperglycemic mice. Stroke 2016;47:1328–35
87. Arakawa M, Mita T, Azuma K, Ebato C, Goto H, Nomiyama T et al. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes 2010;59:1030–7
88. Liu H, Dear AE, Knudsen LB, Simpson RW. A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules. J Endocrinol 2009;201:59–66
89. Lu HY, Huang CY, Shih CM, Chang WH, Tsai CS, Lin FY et al. Dipeptidyl peptidase-4 inhibitor decreases abdominal aortic aneurysm formation through GLP-1-dependent monocytic activity in mice. PLoS One 2015;10:e0121077
90. Koska J, Sands M, Burciu C, D'Souza KM, Raravikar K, Liu J et al. Exenatide protects against glucose- and lipid-induced endothelial dysfunction: evidence for direct vasodilation effect of GLP-1 receptor agonists in humans. Diabetes 2015;64:2624–35
91. Mason RP, Jacob RF, Kubant R, Walter MF, Bellamine A, Jacoby A et al. Effect of enhanced glycemic control with saxagliptin on endothelial nitric oxide release and CD40 levels in obese rats. J Atheroscler Thromb 2011;18:774–83
92. Akita K, Isoda K, Shimada K, Daida H. Dipeptidyl-peptidase-4 inhibitor, alogliptin, attenuates arterial inflammation and neointimal formation after injury in low-density lipoprotein (LDL) receptor-deficient mice. J Am Heart Assoc 2015;4:e001469
93. Matsubara J, Sugiyama S, Akiyama E, Iwashita S, Kurokawa H, Ohba K et al. Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes. Circ J 2013;77:1337–44
94. Jabbour SA. SGLT2 inhibitors to control glycemia in type 2 diabetes mellitus: a new approach to an old problem. Postgrad Med 2014;126:111–7
95. Salim HM, Fukuda D, Yagi S, Soeki T, Shimabukuro M, Sata M. Glycemic control with ipragliflozin, a novel selective SGLT2 inhibitor, ameliorated endothelial dysfunction in streptozotocin-induced diabetic mouse. Front Cardiovasc Med 2016;3:43
96. Naznin F, Sakoda H, Okada T, Tsubouchi H, Waise TM, Arakawa K et al. Canagliflozin, a sodium glucose cotransporter 2 inhibitor, attenuates obesity-induced inflammation in the nodose ganglion, hypothalamus, and skeletal muscle of mice. Eur J Pharmacol 2017;794:37–44
97. Han JH, Oh TJ, Lee G, Maeng HJ, Lee DH, Kim KM et al. The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE-/- mice fed a western diet. Diabetologia 2017;60:364–76
98. Leng W, Ouyang X, Lei X, Wu M, Chen L, Wu Q et al. The SGLT-2 inhibitor dapagliflozin has a therapeutic effect on atherosclerosis in diabetic ApoE-/- mice. Mediators Inflamm 2016;2016:6305735
99. Ishibashi Y, Matsui T, Yamagishi S. Tofogliflozin, a highly selective inhibitor of SGLT2 blocks proinflammatory and proapoptotic effects of glucose overload on proximal tubular cells partly by suppressing oxidative stress generation. Horm Metab Res 2016;48:191–5
100. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–65
101. Selvin E, Bolen S, Yeh HC, Wiley C, Wilson LM, Marinopoulos SS et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 2008;168:2070–80
102. Roussel R, Travert F, Pasquet B, Wilson PW, Smith SC Jr, Goto S et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med 2010;170:1892–9
103. Mita T, Katakami N, Shiraiwa T, Yoshii H, Onuma T, Kuribayashi N 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;39:455–64
104. Mizoguchi M, Tahara N, Tahara A, Nitta Y, Kodama N, Oba T et al. Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes a prospective, randomized, comparator-controlled study using serial FDG PET/CT imaging study of carotid artery and ascending aorta. JACC Cardiovasc Imaging 2011;4:1110–8
105. Kronmal RA, Barzilay JI, Smith NL, Psaty BM, Kuller LH, Burke GL et al. Mortality in pharmacologically treated older adults with diabetes: the Cardiovascular Health Study, 1989–2001. PLoS Med 2006;3:e400
106. Nystrom T, Bodegard J, Nathanson D, Thuresson M, Norhammar A, Eriksson JW. Novel oral glucose-lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes. Diabetes Obes Metab 2017;19:831–41
107. Jensterle M, Sebestjen M, Janez A, Prezelj J, Kocjan T, Keber I et al. Improvement of endothelial function with metformin and rosiglitazone treatment in women with polycystic ovary syndrome. Eur J Endocrinol 2008;159:399–406
108. Formoso G, De Filippis EA, Michetti N, Di Fulvio P, Pandolfi A, Bucciarelli T et al. Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects. Diabetes Metab Res Rev 2008;24:231–7
109. Preiss D, Lloyd SM, Ford I, McMurray JJ, Holman RR, Welsh P et al. Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. Lancet Diabetes Endocrinol 2014;2:116–24
110. Lundby-Christensen L, Tarnow L, Boesgaard TW, Lund SS, Wiinberg N, Perrild H et al. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial. BMJ Open 2016;6:e008376
111. Younis A, Eskenazi D, Goldkorn R, Leor J, Naftali-Shani N, Fisman EZ et al. The addition of vildagliptin to metformin prevents the elevation of interleukin 1ss in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study. Cardiovasc Diabetol 2017;16:69
112. Inayat UR, Khan RU, Khalil Ur R, Bashir M. Lower hypoglycemic but higher antiatherogenic effects of bitter melon than glibenclamide in type 2 diabetic patients. Nutr J 2015;14:13
113. Xiao CC, Ren A, Yang J, Ye SD, Xing XN, Li SM et al. Effects of pioglitazone and glipizide on platelet function in patients with type 2 diabetes. Eur Rev Med Pharmacol Sci 2015;19:963–70
114. Gerstein HC, Ratner RE, Cannon CP, Serruys PW, Garcia-Garcia HM, van Es GA et al. Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation 2010;121:1176–87
115. Han SJ, Hur KY, Kim YS, Kang ES, Kim SI, Kim MS et al. Effects of pioglitazone on subclinical atherosclerosis and insulin resistance in nondiabetic renal allograft recipients. Nephrol Dial Transplant 2010;25:976–84
116. Nicholls SJ, Tuzcu EM, Wolski K, Bayturan O, Lavoie A, Uno K et al. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. J Am Coll Cardiol 2011;57:153–9
117. Nitta Y, Tahara N, Tahara A, Honda A, Kodama N, Mizoguchi M et al. Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging. JACC Cardiovasc Imaging 2013;6:1172–82
118. Koyama H, Tanaka S, Monden M, Shoji T, Morioka T, Fukumoto S et al. Comparison of effects of pioglitazone and glimepiride on plasma soluble RAGE and RAGE expression in peripheral mononuclear cells in type 2 diabetes: randomized controlled trial (PioRAGE). Atherosclerosis 2014;234:329–34
119. Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Wu Y et al. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis 2010;212:223–9
120. Rizzo M, Chandalia M, Patti AM, Di Bartolo V, Rizvi AA, Montalto G et al. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol 2014;13:49
121. Nomoto H, Miyoshi H, Furumoto T, Oba K, Tsutsui H, Miyoshi A et al. A comparison of the effects of the GLP-1 analogue liraglutide and insulin glargine on endothelial function and metabolic parameters: a randomized, controlled trial sapporo athero-incretin study 2 (SAIS2). PLoS One 2015;10:e0135854
122. Barbieri M, Rizzo MR, Marfella R, Boccardi V, Esposito A, Pansini A et al. Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors. Atherosclerosis 2013;227:349–54
123. Ishikawa S, Shimano M, Watarai M, Koyasu M, Uchikawa T, Ishii H et al. Impact of sitagliptin on carotid intima-media thickness in patients with coronary artery disease and impaired glucose tolerance or mild diabetes mellitus. Am J Cardiol 2014;114:384–8
124. Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism 2014;63:1141–8
125. Nakamura K, Oe H, Kihara H, Shimada K, Fukuda S, Watanabe K et al. DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study. Cardiovasc Diabetol 2014;13:110
126. Widlansky ME, Puppala VK, Suboc TM, Malik M, Branum A, Signorelli K et al. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc Med 2017;22:189–96
127. Njerve IU, Akra S, Weiss TW, Solheim S, Ovstebo R, Aass HCD et al. A double-blinded randomized study investigating a possible anti-inflammatory effect of saxagliptin versus placebo as add-on therapy in patients with both type 2 diabetes and stable coronary artery disease. Mediators Inflamm 2017;2017:5380638