title: Antidiabetic treatment, stroke severity and outcome.
abstract: Ischemic stroke is a leading cause of mortality and long-term disability worldwide. Given the detrimental effects of acute stroke, several neuroprotective agents have been evaluated in these patients. However, the benefits of the evaluated agents appear to be limited and none is currently recommended for clinical use. On the other hand, prior treatment with agents that are used for the primary and secondary prevention of stroke, including statins and antiplatelets, has been associated with better outcome in patients who experience an acute stroke. In contrast, there are limited data as to whether prior treatment with antidiabetic agents is beneficial in diabetic patients who suffer a stroke. In this context, the findings of a recent study that showed reduced stroke size following pretreatment with linagliptin, a dipeptidyl peptidase-4 (DDP-4) inhibitor, compared with glimepiride, in both diabetic and non-diabetic mice, appear promising. Despite these preclinical findings suggesting neuroprotective effects of DPP-4 inhibitors in acute stroke, it is still unclear whether these actions will also be observed in humans. Of note, two recent large randomized, placebo-controlled studies did not show any effect of DPP-4 inhibitors on cardiovascular events, including stroke. Several other ongoing trials are evaluating the effects of DPP-4 inhibitors on cardiovascular morbidity and mortality. These studies also provide a major opportunity to assess whether patients treated with this class of antidiabetic agents will suffer from less severe strokes and whether their outcome after stroke will be more favorable.
authors.affiliation: Dimitra Magkou, Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Magkou
authors.affiliation: Dimitra Magkou, Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tziomalos
keywords: Dipeptidyl peptidase-4 inhibitors; Neuroprotection; Stroke; Sulfonylureas; Type 2 diabetes mellitus
references.citation: Int J Stroke. 2013 Oct;8(7):E49
references.pmid: 24024925
references.citation: Neurocrit Care. 2009;10(2):181-6
references.pmid: 18357419
references.citation: Clin Sci (Lond). 2012 May 1;122(10):473-83
references.pmid: 22150224
references.citation: Stroke. 2003 Mar;34(3):688-94
references.pmid: 12624292
references.citation: Postgrad Med. 2010 May;122(3):16-27
references.pmid: 20463410
references.citation: Brain Res. 2012 Jan 3;1427:23-34
references.pmid: 22055454
references.citation: Diabetes. 2013 Apr;62(4):1289-96
references.pmid: 23209191
references.citation: N Engl J Med. 2013 Oct 3;369(14):1327-35
references.pmid: 23992602
references.citation: Endocrinology. 2005 Apr;146(4):2055-9
references.pmid: 15604213
references.citation: J Mol Neurosci. 2002 Feb-Apr;18(1-2):7-14
references.pmid: 11931352
references.citation: Cochrane Database Syst Rev. 2011 Sep 07;(9):CD005346
references.pmid: 21901697
references.citation: Brain Res. 2013 Jun 23;1517:104-13
references.pmid: 23602966
references.citation: Diabet Med. 2013 Oct;30(10):1160-71
references.pmid: 23663156
references.citation: Nat Med. 2006 Apr;12(4):433-40
references.pmid: 16550187
references.citation: Stroke. 2011 Mar;42(3):710-5
references.pmid: 21330623
references.citation: Int J Stroke. 2012 Jul;7(5):407-18
references.pmid: 22394615
references.citation: Neurology. 2002 Sep 10;59(5):669-74
references.pmid: 12221155
references.citation: J Neurochem. 2005 Feb;92(4):798-806
references.pmid: 15686481
references.citation: Ann Intern Med. 2012 Nov 6;157(9):601-10
references.pmid: 23128859
references.citation: Regul Pept. 1999 Nov 30;85(1):9-24
references.pmid: 10588446
references.citation: Stroke. 2013 Feb;44(2):448-56
references.pmid: 23287777
references.citation: Lancet. 2008 May 10;371(9624):1612-23
references.pmid: 18468545
references.citation: N Engl J Med. 2013 Oct 3;369(14):1317-26
references.pmid: 23992601
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1285-90
references.pmid: 19164583
references.citation: J Pharmacol Exp Ther. 2004 May;309(2):469-75
references.pmid: 14724226
references.citation: Neurology. 2006 Feb 14;66(3):319-23
references.pmid: 16382033
references.citation: Behav Pharmacol. 2010 Sep;21(5-6):394-408
references.pmid: 20574409
references.citation: Stroke. 2007 Sep;38(9):2526-30
references.pmid: 17673715
references.citation: Lancet. 2012 Aug 4;380(9840):475-83
references.pmid: 22748821
references.citation: Stroke. 2000 Jun;31(6):1411-7
references.pmid: 10835464
references.citation: Stroke. 2001 Sep;32(9):2029-32
references.pmid: 11546892
references.citation: J Diabetes Complications. 2009 Jul-Aug;23(4):283-96
references.pmid: 18358748
references.citation: Stroke. 2010 May;41(5):e409-17
references.pmid: 20224058
references.citation: J Cereb Blood Flow Metab. 2011 Aug;31(8):1696-705
references.pmid: 21487412
references.citation: Neurochem Res. 2007 Apr-May;32(4-5):635-8
references.pmid: 16960755
references.citation: Neuroscience. 2012 May 3;209:171-86
references.pmid: 22402345
references.citation: Curr Vasc Pharmacol. 2008 Apr;6(2):124-33
references.pmid: 18393914
references.citation: Stroke. 2001 Oct;32(10):2426-32
references.pmid: 11588337
references.citation: Endocrinology. 2000 Apr;141(4):1301-9
references.pmid: 10746632
references.citation: Neuroreport. 2009 Aug 26;20(13):1161-6
references.pmid: 19617854
references.citation: Lancet. 2011 Jul 9;378(9786):169-81
references.pmid: 21705072
references.citation: Stroke. 2009 Feb;40(2):604-9
references.pmid: 19023097
references.citation: J Neurosci Res. 2011 Jul;89(7):1103-13
references.pmid: 21472764
references.citation: Int J Obes Relat Metab Disord. 2003 Mar;27(3):313-8
references.pmid: 12629557
references.citation: FEBS Lett. 1995 Jan 30;358(3):219-24
references.pmid: 7843404
references.citation: J Clin Endocrinol Metab. 2013 Feb;98(2):668-77
references.pmid: 23372169
references.citation: Ann Neurol. 2010 May;67(5):570-8
references.pmid: 20437554
references.citation: Lancet. 2010 Jun 26;375(9733):2215-22
references.pmid: 20609967
references.citation: Lancet Neurol. 2007 May;6(5):397-406
references.pmid: 17434094
references.citation: Curr Opin Neurol. 2011 Feb;24(1):81-8
references.pmid: 21124220
references.citation: Lancet Neurol. 2012 Mar;11(3):261-71
references.pmid: 22341034