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Cardiovascular Drugs and Therapy

Published in:

01-06-2008

Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance

Authors: Markolf Hanefeld, Frank Schaper, Carsta Koehler

Published in: Cardiovascular Drugs and Therapy | Issue 3/2008

Abstract

Introduction

Excessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of α-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation.

Results and discussion

Flow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events.

Conclusion

Thus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.

Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434–44.PubMedCrossRef

Wallander M, Bartnik M, Efendic S, Hamsten A, Malmberg K, Ohrvik J, Ryden L, Silveira A, Norhammar A. Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study. Diabetologia 2005;48:2229–35.PubMedCrossRef

Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 1999;34:146–54.PubMedCrossRef

Scognamiglio R, Negut C, De Kreutzenberg SV, Tiengo A, Avogaro A. Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation 2005;112:179–84.PubMedCrossRef

Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, Ziegelasch HJ, Lindner J, the DIS Group. Risk factors for myocardial infarction and death in newly detected NIDDM: The Diabetes Intervention Study, 11 years follow-up. Diabetologia 1996;39:1577–83.PubMedCrossRef

DECODE Study Group, European Diabetes Epidemiology Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care 2003;26:688–96.CrossRef

Guideline for management of postmeal glucose. International Diabetes Federation, 2007. Belgien, http://www.idf.org.

Salsburg DS. The UGDP study. JAMA 1971;218:1704–5.PubMedCrossRef

Puls W, Keup U, Krause HP, Thomas G, Hoffmeister F. Glucosidase inhibition. A new approach to the treatment of diabetes, obesity and hyperlipoproteinemia. Naturwissenschaften 1977;64:536–7.PubMedCrossRef

10.

Schmidt DD, Frommer W, Junge B Müller L, Wingender W, Truscheit E, Schäfer D. Alpha-glucosidase inhibitors. New complex oligosaccharides of microbial origin. Naturwissenschaften 1977;64:535–6.PubMedCrossRef

11.

Hanefeld M. The role of alpha-glucosidase inhibitors (acarbose). In: Mogensen CE, editor. Pharmacotherapy of diabetes: new development. Berlin, Springer, 2007. pp. 143–152.

12.

Esposito K, Guiliano D, et al. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation 2004;110:214–9.PubMedCrossRef

13.

Joubert PH, Venter HL, Foukaridis GN. The effect of miglitol and acarbose after an oral glucose load: a novel hypoglycaemic mechanism. Br J Clin Pharmacol 1990;30:391–6.PubMed

14.

Van de Laar FA, Lucassen PL, Akkermans RP, van de Lisdonk EH, Rutten GE, van Weel C. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care 2005;28:154–63.PubMedCrossRef

15.

Mertes G. Safety and efficacy of acarbose in the treatment of Type 2 Diabetes: data from 5-year surveillance study. Diabetes Res Clin Pract 2001;2:193–204.CrossRef

16.

Chiasson JL, Josse RG, Hunt JA, Palmason C, Rodger NW, Ross SA, Ryan EA, Tan MH, Wolever TM. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. Ann Intern Med 1994;121:928–35.PubMed

17.

Holman RR, Cull CA, Turner RC. A randomised double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care 1999;22:960–4.PubMedCrossRef

18.

Chiasson JL. Prevention of type 2 diabetes: fact or fiction? Expert Opin Pharmacother 2007;8:3147–58.PubMedCrossRef

19.

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.PubMedCrossRef

20.

Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V, Indian Diabetes Prevention Programme (IDPP). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006;49:289–97.PubMedCrossRef

21.

DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial InvestigatorsGerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman RR. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006;368:1096–105.PubMedCrossRef

22.

Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002;359:2072–7.PubMedCrossRef

23.

Yang WY, Lin L, Qi J. [The preventive affect of acarbose and metformin on the IGT population from diabetes mellitus: a 3-year multicentre prospective trial]. Chin J Endocrinol Metab 2001;17:131–6.

24.

Hanefeld M, Karasik A, Koehler C, Westermeier T, Saunders G, Chiasson JL. Metabolic syndrome and its single traits as risk factors of diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial. Diabetes Care. 2008 (Submitted).

25.

Yudkin JS. Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology. Diabetologia. 2007;50:1576–86.PubMedCrossRef

26.

Meneilly G, Ryan EA, Radziuk J, Lau DC, Yale JF, Morais J, Chiasson JL, Rabasa-Lhoret R, Maheux P, Tessier D, Wolever T, Josse RG, Elahi D. Effect of acarbose on insulin sensitivity in elderly patients with diabetes. Diabetes Care. 2000;23:1162–7.PubMedCrossRef

27.

Chiasson JL, Josse RG, Leiter LA, Mihic M, Nathan DM, Palmason C, Cohen RM, Wolever TM. The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance. Diabetes Care. 1996;19:1190–3.PubMedCrossRef

28.

Laube H, Linn T, Heyen P. The effects of acarbose on insulin sensitivity and proinsulin in overweight subjects with impaired glucose tolerance. Exp Clin Endocrinol Diabetes. 1998;106:231–3.PubMedCrossRef

29.

Hanefeld M, Haffner SM, Menschikowski M, Koehler C, Temelkova-Kurktschiev T, Wildbrett J, Fischer S. Different effects of acarbose and glibenclamide on proinsulin and insulin profiles in people with type 2 diabetes. Diabetes Res Clin Pract. 2002;55:221–7.PubMedCrossRef

30.

Qualmann C, Nauck MA, Hoist JJ, Orskov C, Creutzfeldt W. Glucagon-like peptide 1 (17–36 amide) secretion in response to luminal sucrose from the upper and lower gut: a study using a-glucosidase inhibition (acarbose). Scand J Gastroenterol. 1995;30:892–6.PubMedCrossRef

31.

Seifarth C, Bergmann J, Holst JJ, Ritzel R, Schmiegel W, Nauck MA. Prolonged and enhanced secretion of glucagon-like peptide 1 (7–36 Amide) after oral sucrose due to α-glucosidase inhibition (acarbose) in type 2 diabetic patients. Diabet Med. 1998;15:485–91.PubMedCrossRef

32.

Lindström J, Tuomilehto J, Spengler M. Acarbose treatment does not change the habitual diet of patients with type 2 diabetes mellitus. The Finnish Acarbose Study Group. Diabet Med 2000;17:20–5.PubMedCrossRef

33.

Leboritz HE. A-glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Rev. 1998;6:132–45.

34.

Wolever TMS, Chiasson JL, Josse R, Hunt JA, Palmason C, Rodger NW, Ross SA, Ryan EA, Tan MH. Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes. Int J Obes Relat Metab Disord. 1997;21:756–63.PubMedCrossRef

35.

Rosenbaum P, Peres RB, Zanella MT, Ferreira SR. Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure. Braz J Med Biol Res. 2002;35:877–84.PubMedCrossRef

36.

Rosenthal JH, Mauersberger H. Effects on blood pressure of the alpha-glucosidase inhibitor acarbose compared with the insulin enhancer glibenclamide in patients with hypertension and type 2 diabetes mellitus. Clin Drug Invest. 2002;22:695–701.CrossRef

37.

Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003;290:486–94.PubMedCrossRef

38.

Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004;25:10–6.PubMedCrossRef

39.

Hanefeld M, Fischer S, Schulze J, Spengler M, Wargenau M, Schollberg K, Fucker K. Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone. Diabetes Care. 1991;14:732–7.PubMedCrossRef

40.

Leonhardt W, Hanefeld M, Fischer S, Schulze J. Efficacy of alpha-glucosidase inhibitors on lipids in NIDDM subjects with moderate hyperlipidaemia. Eur J Clin Invest. 1994;24:45–9.PubMedCrossRef

41.

Inoue I, Shinoda Y, Nakano T, Sassa M, Goto S, Awata T, Komoda T, Katayama S. Acarbose ameliorates atherogenecity of low-density lipoprotein in patients with impaired glucose tolerance. Metabolism. 2006;55:946–52.PubMedCrossRef

42.

Heine RJ, Dekker JM. Beyond postprandial hyperglycaemia: metabolic factors associated with cardiovascular disease. Diabetologia. 2002;45:461–75.PubMedCrossRef

43.

Rudofsky G, Reismann P, Schiekofer S, Petrov D, van Eynatten M, Humpert PM, Müller-Hoff C, Thanh-Phuong T, Lichtenstein S, Bärtsch U, Hamann A, Nawroth P, Bierhaus A. Reduction of postprandial hyperglycemia in patients with type 2 diabetes reduces NF-κB activation in PBMCs. Horm Met Res. 2004;36:630–38.CrossRef

44.

Tschoepe D. Decreased fibrinogen by treatment with the alpha-glucosidase inhibitor acarbose. Diabetes. 2004;53:A189.

45.

Schäfer A, Widder J, Eigenthaler M, Bischoff H, Ertl G, Bauersachs J. Increased platelet activation in young Zucker rats with impaired glucose tolerance is improved by acarbose. Thromb Haemost. 2004;92:97–103.PubMed

46.

Ceriello A, Taboga C, Tonutti L, Giacomello R, Stel L, Motz E, Pirisi M. Post-meal coagulation activation in diabetes mellitus: the effect of acarbose. Diabetologia. 1996;39:469–73.PubMedCrossRef

47.

Wang X, Lu J, Pan C. Comparison of serum C-reactive protein level in different glucose tolerance subjects and the change in serum CRP level in IGT subjects with acarbose. Chin J Endocrinol Metab. 2003;19:254–6.

48.

Koehler C, Schaper F, Bergmann S, Hanefeld M. Effect of acarbose on subclinical inflammation and immune-response in early type 2 diabetes and risk of atherosclerosis (AI(I)DA) study. Diab Vasc Dis Res. 2007;4:S152.

49.

Wascher TC, Schmoelzer I, Wiegratz A, Stuehlinger M, Mueller-Wieland D, Kotzka J, Enderle M. Reduction of postchallenge hyperglycaemia prevents acute endothelial dysfunction in subjects with impaired glucose tolerance. Eur J Clin Invest. 2005;35:551–7.PubMedCrossRef

50.

Hanefeld M, Chiasson JL, Koehler C, Henkel E, Schaper F, Temelkova-Kurktschiev T. Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke. 2004;35:1073–8.PubMedCrossRef

51.

Ludwig M, Kraft K, Rucker W, Huther AM. [Diagnosis of very early arteriosclerotic vascular wall changes using duplex sonography]. Klin Wochenschr. 1989;67:442–6.PubMedCrossRef

52.

Zeymer U, Schwarzmaier-D’assie A, Petzinna D, Chiasson JL. Effect of acarbose treatment on the risk of silent myocardial infarctions in patients with impaired glucose tolerance: results of the randomised STOP-NIDDM trial electrocardiography substudy. Eur J Cardiovasc Prev Rehabil. 2004;11:412–5.PubMedCrossRef

53.

May C. Efficacy and tolerability of step wise increasing dosage of acarbose in patients with non-insulin-dependent diabetes (NIDDM) treated with sulfonylureas. Diabetes Stoffwechsel. 1995;4:3–7.

54.

Laube H. Acarbose: an update of its therapeutic use in diabetes treatment. Clin Drug Invest. 2002;22:141–56.CrossRef

55.

Hollander P. Safety profile of acarbose, an alpha-glucosidase inhibitor. Drugs. 1992;44(Suppl 3):47–53.PubMed

56.

Laube H. Acarbose: an update of its therapeutic use in diabetes treatment. Clin Drug Invest. 2002;22:141–56.CrossRef

57.

Gentile S, Turco S, Guarino G, Sasso FC, Torella R. Aminotransferase activity and acarbose treatment in patients with type 2 diabetes. Diabetes Care. 1999;22:1217–8.PubMedCrossRef

58.

Hollander P. Safety profile of acarbose, an alpha-glucosidase inhibitor. Drugs. 1992;44(Suppl 3):47–53.PubMedCrossRef

59.

Andrade RJ, Lucena MI, Rodriguez-Mendizabal M. Hepatic injury caused by acarbose. Ann Intern Med. 1996;124:931.PubMed

60.

Carrascosa M, Pascual F, Aresti S. Acarbose-induced acute severe hepatotoxicity. Lancet. 1997;349:698–9.PubMedCrossRef

Title: Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance
Authors: Markolf Hanefeld
Frank Schaper
Carsta Koehler
Publication date: 01-06-2008
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 3/2008
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-008-6091-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance

Abstract

Introduction

Results and discussion

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Results and discussion

Conclusion

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