title: On the potential of acarbose to reduce cardiovascular disease.
abstract: In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted - though not undisputed - the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.
authors.affiliation: Munich Diabetes Research Group e,V, at Helmholtz Centre, Ingolstaedter Landstrasse 1, 85764 Munich, Neuherberg, Germany. Eberhard.Standl@lrz.uni-muenchen.de.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Standl
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Theodorakis
authors.forename: Michael
authors.initials: M
authors.lastname: Erbach
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
mesh_terms: D020909:Acarbose / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D020909:Acarbose
references.citation: J Am Coll Cardiol. 2013 Sep 3;62(10):921-5
references.pmid: 23850922
references.citation: Diabetes Res Clin Pract. 1998 Jul;41(1):49-55
references.pmid: 9768372
references.citation: BMJ Open. 2012 Nov 30;2(6):
references.pmid: 23204139
references.citation: Diabet Med. 2008 Apr;25(4):435-41
references.pmid: 18341596
references.citation: Diabetes Obes Metab. 2012 Mar;14(3):283-7
references.pmid: 22051162
references.citation: JAMA. 2003 Jul 23;290(4):486-94
references.pmid: 12876091
references.citation: Diabetes Obes Metab. 2011 Mar;13(3):221-8
references.pmid: 21205121
references.citation: Diabetes Obes Metab. 2007 Nov;9(6):853-8
references.pmid: 17924867
references.citation: Cardiovasc Diabetol. 2010 Mar 24;9:12
references.pmid: 20334663
references.citation: Clin Drug Investig. 2005;25(9):589-95
references.pmid: 17532703
references.citation: Diabetes Res Clin Pract. 2013 Jan;99(1):e1-2
references.pmid: 23146372
references.citation: Diabetologia. 2012 Jun;55(6):1577-96
references.pmid: 22526604
references.citation: Diab Vasc Dis Res. 2012 Jul;9(3):163-9
references.pmid: 22508699
references.citation: J Clin Endocrinol Metab. 2006 Mar;91(3):837-42
references.pmid: 16368744
references.citation: N Engl J Med. 2013 Oct 3;369(14):1327-35
references.pmid: 23992602
references.citation: Clin Drug Investig. 2007;27(6):397-405
references.pmid: 17506590
references.citation: Diabetes Obes Metab. 2009 Mar;11(3):213-22
references.pmid: 18564177
references.citation: Diabetes Obes Metab. 2004 Mar;6(2):133-56
references.pmid: 14746579
references.citation: Diabetes Res Clin Pract. 2005 Mar;67(3):204-10
references.pmid: 15713352
references.citation: J Thromb Haemost. 2010 Apr;8(4):828-37
references.pmid: 20088941
references.citation: Circulation. 2007 Jul 10;116(2):151-7
references.pmid: 17576864
references.citation: Diabetes Care. 2000 Jan;23(1):45-50
references.pmid: 10857967
references.citation: J Diabetes Complications. 2011 Sep-Oct;25(5):332-8
references.pmid: 21813293
references.citation: Diabetes Res Clin Pract. 2011 Apr;92(1):57-64
references.pmid: 21251726
references.citation: Lancet. 2002 Jun 15;359(9323):2072-7
references.pmid: 12086760
references.citation: Acta Diabetol. 2012 Jun;49(3):225-30
references.pmid: 21898126
references.citation: JAMA. 2003 Dec 17;290(23):3066-7; author reply 3067-9
references.pmid: 14679261
references.citation: Diabetes Metab Syndr Obes. 2012;5:357-67
references.pmid: 23093911
references.citation: N Engl J Med. 2013 Oct 3;369(14):1317-26
references.pmid: 23992601
references.citation: N Engl J Med. 2012 Jul 26;367(4):319-28
references.pmid: 22686416
references.citation: Lancet. 1999 Aug 21;354(9179):617-21
references.pmid: 10466661
references.citation: Diabetologia. 2011 May;54(5):1219-26
references.pmid: 21287141
references.citation: N Engl J Med. 2008 Jun 12;358(24):2545-59
references.pmid: 18539917
references.citation: Atherosclerosis. 2011 Sep;218(1):214-9
references.pmid: 21640349
references.citation: Diabet Med. 2010 Dec;27(12):1436-42
references.pmid: 21059097
references.citation: Diabet Med. 2005 Feb;22(2):158-63
references.pmid: 15660732
references.citation: Circulation. 2004 Jul 13;110(2):214-9
references.pmid: 15197140
references.citation: Diabetes Care. 2005 Jan;28(1):154-63
references.pmid: 15616251
references.citation: Lancet. 1998 Sep 12;352(9131):854-65
references.pmid: 9742977
references.citation: Diabetes Technol Ther. 2012 Aug;14(8):736-40
references.pmid: 22853724
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G752-63
references.pmid: 11518688
references.citation: J Gerontol A Biol Sci Med Sci. 2011 Aug;66(8):917-24
references.pmid: 21628676
references.citation: Ann Intern Med. 1994 Dec 15;121(12):928-35
references.pmid: 7734015
references.citation: Horm Metab Res. 2009 Feb;41(2):132-6
references.pmid: 19214923
references.citation: Stroke. 2004 May;35(5):1073-8
references.pmid: 15073402
references.citation: Diabet Med. 2004 Mar;21(3):208-13
references.pmid: 15008828
references.citation: Adv Ther. 2012 Sep;29(9):736-46
references.pmid: 22923161
references.citation: Nature. 2012 Oct 4;490(7418):55-60
references.pmid: 23023125
references.citation: Diabetes. 2013 May;62(5):1697-708
references.pmid: 23364453
references.citation: JAMA. 2006 Apr 12;295(14):1681-7
references.pmid: 16609090
references.citation: Diabetes Res Clin Pract. 2004 Dec;66 Suppl 1:S169-72
references.pmid: 15563971
references.citation: Clin Ther. 2010 Aug;32(9):1610-7
references.pmid: 20974318
references.citation: Eur J Clin Invest. 2005 Sep;35(9):551-7
references.pmid: 16128861
references.citation: J Res Med Sci. 2013 May;18(5):391-4
references.pmid: 24174943
references.citation: J Atheroscler Thromb. 2008 Jun;15(3):154-9
references.pmid: 18603822
references.citation: Diabetologia. 2009 Mar;52(3):415-24
references.pmid: 19130039
references.citation: Circ Cardiovasc Qual Outcomes. 2009 May;2(3):279-85
references.pmid: 20031849
references.citation: Diabetes Care. 1999 Jun;22(6):960-4
references.pmid: 10372249
references.citation: Scand J Gastroenterol. 1995 Sep;30(9):892-6
references.pmid: 8578189
references.citation: Diabetes. 2008 May;57(5):1349-54
references.pmid: 18299315
references.citation: J Pharmacol Sci. 2010;114(1):32-40
references.pmid: 20703014
references.citation: Diabetes Obes Metab. 2010 Apr;12(4):288-98
references.pmid: 20380649
references.citation: Circ Heart Fail. 2013 Mar;6(2):203-10
references.pmid: 23388113
references.citation: Clin Exp Nephrol. 2011 Feb;15(1):58-63
references.pmid: 20824296
references.citation: J Clin Endocrinol Metab. 2008 Apr;93(4):1345-50
references.pmid: 18198229
references.citation: Endocr J. 2013;60(4):431-9
references.pmid: 23220949
references.citation: Diabetes Care. 2011 May;34 Suppl 2:S120-7
references.pmid: 21525442
references.citation: Cardiovasc Diabetol. 2013 May 04;12:73
references.pmid: 23642288
references.citation: Circulation. 2007 Oct 23;116(17):1942-51
references.pmid: 17965405
references.citation: Stroke. 2013 Sep;44(9):2590-3
references.pmid: 23899915
references.citation: J Clin Epidemiol. 1991;44(2):183-90
references.pmid: 1995775
references.citation: Cardiovasc Diabetol. 2013 Jun 19;12:92
references.pmid: 23777506
references.citation: Eur Heart J. 2013 Oct;34(39):3035-87
references.pmid: 23996285
references.citation: J Hypertens. 2012 Jul;30(7):1440-3
references.pmid: 22573126
references.citation: Diabetes Res Clin Pract. 1995 May;28(2):103-17
references.pmid: 7587918
references.citation: Diabetes Metab Res Rev. 2013 Oct;29(7):582-91
references.pmid: 23908125
references.citation: Horm Metab Res. 2009 Feb;41(2):104-8
references.pmid: 19061152
references.citation: Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E550-9
references.pmid: 16219666
references.citation: Eur Heart J. 2004 Jan;25(1):10-6
references.pmid: 14683737
references.citation: N Engl J Med. 2014 Jan 30;370(5):483
references.pmid: 24476445
references.citation: Diabetes Care. 2006 Jan;29(1):95-100
references.pmid: 16373903
references.citation: Diabetologia. 2011 Jan;54(1):69-72
references.pmid: 20886203
references.citation: Horm Metab Res. 2004 Sep;36(9):630-8
references.pmid: 15486815
references.citation: Diabetes Care. 2011 May;34 Suppl 2:S251-7
references.pmid: 21525464
references.citation: JAMA. 2003 Dec 17;290(23):3066; author reply 3067-9
references.pmid: 14679260
references.citation: Diabetes Care. 1999 Feb;22(2):233-40
references.pmid: 10333939
references.citation: Lancet. 2004 Sep 11-17;364(9438):937-52
references.pmid: 15364185
references.citation: Clin Chim Acta. 2008 Apr;390(1-2):110-4
references.pmid: 18230353
references.citation: Diabetes Care. 1999 Jun;22(6):920-4
references.pmid: 10372242
references.citation: Clin Ther. 2013 Jun;35(6):880-99
references.pmid: 23602502
references.citation: Diabetes Res Clin Pract. 2003 May;60(2):111-8
references.pmid: 12706319
references.citation: Expert Rev Cardiovasc Ther. 2008 Feb;6(2):153-63
references.pmid: 18248270
references.citation: Diabetologia. 2004 Mar;47(3):385-394
references.pmid: 14985967
references.citation: Diabetes Care. 1995 Jul;18(7):928-32
references.pmid: 7555551
references.citation: Clin Invest Med. 1995 Aug;18(4):303-11
references.pmid: 8549017
references.citation: Eur Heart J. 2012 Jun;33(12):1491-9
references.pmid: 21920963
references.citation: Diabetologia. 1996 Dec;39(12):1577-83
references.pmid: 8960845
references.citation: Lancet Diabetes Endocrinol. 2014 Jan;2(1):46-55
references.pmid: 24622668
references.citation: J Clin Endocrinol Metab. 2006 Mar;91(3):813-9
references.pmid: 16352690
references.citation: Int J Cardiol. 2013 Sep 1;167(5):2108-13
references.pmid: 22721642
references.citation: Nature. 2013 Jun 6;498(7452):99-103
references.pmid: 23719380
references.citation: J Neurol. 2013 Feb;260(2):475-83
references.pmid: 22983428
references.citation: Diabetes Metab Res Rev. 1999 Jul-Aug;15(4):289-96
references.pmid: 10495478
references.citation: Diabetologia. 2011 Jan;54(1):10-8
references.pmid: 20871975
references.citation: Diabet Med. 2000 Jan;17(1):20-5
references.pmid: 10691155