Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 3/2008

01.06.2008

Metformin: Effects on Micro and Macrovascular Complications in Type 2 Diabetes

verfasst von: Clifford J. Bailey

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 3/2008

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The antihyperglycaemic agent metformin is widely used in the treatment of type 2 diabetes. Data from the UK Prospective Diabetes Study and retrospective analyses of large healthcare databases concur that metformin reduces the incidence of myocardial infarction and increases survival in these patients. This apparently vasoprotective effect appears to be independent of the blood glucose-lowering efficacy.

Effects of metformin

Metformin has long been known to reduce the development of atherosclerotic lesions in animal models, and clinical studies have shown the drug to reduce surrogate measures such as carotid intima-media thickness. The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity. There may be modest favourable effects against dyslipidaemia, reductions in pro-inflammatory cytokines and monocyte adhesion molecules, and improved glycation status, benefiting endothelial function in the macro- and micro-vasculature. Additionally metformin exerts anti-thrombotic effects, contributing to overall reductions in athero-thrombotic risk in type 2 diabetic patients.
Literatur
1.
Zurück zum Zitat Bailey CJ, Campbell IW, Chan JCN, et al. Metformin. The gold standard. Chichester: Wiley; 2007. p. 288. Bailey CJ, Campbell IW, Chan JCN, et al. Metformin. The gold standard. Chichester: Wiley; 2007. p. 288.
2.
Zurück zum Zitat Nathan DM, Buse JB, Davidson MB, Heine RJ, et al. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetologia. 2006;49:1711–21.PubMedCrossRef Nathan DM, Buse JB, Davidson MB, Heine RJ, et al. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetologia. 2006;49:1711–21.PubMedCrossRef
3.
Zurück zum Zitat Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65:384–411.CrossRef Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65:384–411.CrossRef
6.
Zurück zum Zitat Wiernsperger NF, Bailey CJ. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs. 1999;58:31–9.PubMedCrossRef Wiernsperger NF, Bailey CJ. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs. 1999;58:31–9.PubMedCrossRef
7.
Zurück zum Zitat Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167–74.PubMed Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167–74.PubMed
8.
Zurück zum Zitat Cusi K, DeFronzo RA. Metformin: a review of its metabolic effects. Diabetes Revs. 1998;6:89–130. Cusi K, DeFronzo RA. Metformin: a review of its metabolic effects. Diabetes Revs. 1998;6:89–130.
9.
Zurück zum Zitat Howlett HCS, Bailey CJ. Risk-benefit assessment of metformin in type 2 diabetes. Drug Safety. 1999;20:489–503.PubMedCrossRef Howlett HCS, Bailey CJ. Risk-benefit assessment of metformin in type 2 diabetes. Drug Safety. 1999;20:489–503.PubMedCrossRef
10.
Zurück zum Zitat Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis. Epidemiology, pathophysiology and management. JAMA. 2002;287:2570–81.PubMedCrossRef Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis. Epidemiology, pathophysiology and management. JAMA. 2002;287:2570–81.PubMedCrossRef
11.
12.
Zurück zum Zitat UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef
13.
Zurück zum Zitat UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–65.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–65.CrossRef
14.
Zurück zum Zitat Holman RR. Invited presentation at 18th International Diabetes Federation Congress, Paris, 2003. Holman RR. Invited presentation at 18th International Diabetes Federation Congress, Paris, 2003.
15.
Zurück zum Zitat Kao J, Tobis J, McClelland RL, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004;93:1347–50.PubMedCrossRef Kao J, Tobis J, McClelland RL, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004;93:1347–50.PubMedCrossRef
16.
Zurück zum Zitat Kahn SE, Haffner SM, Heise MA, Herman WH, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–43.PubMedCrossRef Kahn SE, Haffner SM, Heise MA, Herman WH, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–43.PubMedCrossRef
17.
Zurück zum Zitat Cleland JGF, Atkin SL. Thiazolidinediones, deadly sins, surrogates and elephants. Lancet. 2007;370:1103–4.PubMedCrossRef Cleland JGF, Atkin SL. Thiazolidinediones, deadly sins, surrogates and elephants. Lancet. 2007;370:1103–4.PubMedCrossRef
18.
Zurück zum Zitat Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–8.PubMedCrossRef Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–8.PubMedCrossRef
19.
Zurück zum Zitat Evans JM, Ogston SA, Emslie-Smith MA, Morris A. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulphonylureas and metformin. Diabetologia. 2006;49:930–6.PubMedCrossRef Evans JM, Ogston SA, Emslie-Smith MA, Morris A. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulphonylureas and metformin. Diabetologia. 2006;49:930–6.PubMedCrossRef
20.
Zurück zum Zitat Nichols GA, Koro CE, Gullion CM, et al. The incidence of congestive heart failure associated with antidiabetic therapies. Diabetes Metab Res Rev. 2005;21:51–7.PubMedCrossRef Nichols GA, Koro CE, Gullion CM, et al. The incidence of congestive heart failure associated with antidiabetic therapies. Diabetes Metab Res Rev. 2005;21:51–7.PubMedCrossRef
21.
Zurück zum Zitat McAfee AT, Koro C, Landon J, et al. Coronary heart disease outcomes in patients receiving antidiabetic agents. Pharmacoepidemiol Drug Safety. 2007;16:711–25.CrossRef McAfee AT, Koro C, Landon J, et al. Coronary heart disease outcomes in patients receiving antidiabetic agents. Pharmacoepidemiol Drug Safety. 2007;16:711–25.CrossRef
22.
Zurück zum Zitat Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care. 2002;25:2244–8.PubMedCrossRef Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care. 2002;25:2244–8.PubMedCrossRef
23.
Zurück zum Zitat Johnson JA, Simpson SH, Toth EL, Majumbar SR. Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with type 2 diabetes. Diabetic Med. 2005;22:497–502.PubMedCrossRef Johnson JA, Simpson SH, Toth EL, Majumbar SR. Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with type 2 diabetes. Diabetic Med. 2005;22:497–502.PubMedCrossRef
24.
Zurück zum Zitat Eurich DT, Majumdar SR, McAlister FA, et al. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28:2345–51.PubMedCrossRef Eurich DT, Majumdar SR, McAlister FA, et al. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28:2345–51.PubMedCrossRef
25.
Zurück zum Zitat Masudi FA, Inzucchi SE, Wang Y, et al. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005;111:583–90.CrossRef Masudi FA, Inzucchi SE, Wang Y, et al. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005;111:583–90.CrossRef
27.
Zurück zum Zitat Roberts F, Ryan GJ. The safety of metformin in heart failure. Ann Pharmacother. 2007;41:462–6. Roberts F, Ryan GJ. The safety of metformin in heart failure. Ann Pharmacother. 2007;41:462–6.
28.
Zurück zum Zitat Jones GC, Macklin JP, Alexander WD. Contraindications to the use of metformin. Br Med J. 2003;326:4–5.CrossRef Jones GC, Macklin JP, Alexander WD. Contraindications to the use of metformin. Br Med J. 2003;326:4–5.CrossRef
29.
Zurück zum Zitat Inzucchi SE. Metformin and heart failure: innocent until proven guilty. Diabetes Care. 2005;28:2585–7.PubMedCrossRef Inzucchi SE. Metformin and heart failure: innocent until proven guilty. Diabetes Care. 2005;28:2585–7.PubMedCrossRef
30.
Zurück zum Zitat Holstein A, Stumvoll M. Contraindications can damage your health—is metformin a case in point? Diabetologia. 2005;48:2454–9.PubMedCrossRef Holstein A, Stumvoll M. Contraindications can damage your health—is metformin a case in point? Diabetologia. 2005;48:2454–9.PubMedCrossRef
31.
Zurück zum Zitat Katakami N, Yamaski Y, Hayaishi-Okano R, et al. Metformin and gliclazide rather than glibenclamide attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Diabetologia. 2004;47:1906–13.PubMedCrossRef Katakami N, Yamaski Y, Hayaishi-Okano R, et al. Metformin and gliclazide rather than glibenclamide attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Diabetologia. 2004;47:1906–13.PubMedCrossRef
32.
Zurück zum Zitat Matsumoto K, Sera Y, Abbe Y, et al. Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Prac. 2004;64:2205–8.CrossRef Matsumoto K, Sera Y, Abbe Y, et al. Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Prac. 2004;64:2205–8.CrossRef
33.
Zurück zum Zitat Orio F, Palomba S, Cascella T, et al. Improvement in endothelial structure and function after metformin treatment in young normal weight women with polycystic ovary syndrome: results of a 6-month study. J Clin Endocrinol Metab. 2005;90:6072–6.PubMedCrossRef Orio F, Palomba S, Cascella T, et al. Improvement in endothelial structure and function after metformin treatment in young normal weight women with polycystic ovary syndrome: results of a 6-month study. J Clin Endocrinol Metab. 2005;90:6072–6.PubMedCrossRef
34.
Zurück zum Zitat Li L, Mamputu JC, Wiernsperger N, Renier G. Signalling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes. 2005;54:2227–34.PubMedCrossRef Li L, Mamputu JC, Wiernsperger N, Renier G. Signalling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes. 2005;54:2227–34.PubMedCrossRef
35.
Zurück zum Zitat Sirtori CR, Franceschini G, Gianfranceschi G, et al. Metformin improves peripheral vascular in nonhyperlipidemic patients with arterial disease. J Cardiovasc Pharmacol. 1984;6:914–23.PubMedCrossRef Sirtori CR, Franceschini G, Gianfranceschi G, et al. Metformin improves peripheral vascular in nonhyperlipidemic patients with arterial disease. J Cardiovasc Pharmacol. 1984;6:914–23.PubMedCrossRef
36.
Zurück zum Zitat Montaguti U, Cellin D, Ceredi C, Descovitch GC. Efficacy of the long-term administration of metformin in hyperlipidaemic patients. Res Clin Forums. 1979;1:95–103. Montaguti U, Cellin D, Ceredi C, Descovitch GC. Efficacy of the long-term administration of metformin in hyperlipidaemic patients. Res Clin Forums. 1979;1:95–103.
37.
Zurück zum Zitat Wheatcroft SB, Williams IL, Shah AM, Kearney MT. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabetic Med. 2003;20:255–68.PubMedCrossRef Wheatcroft SB, Williams IL, Shah AM, Kearney MT. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabetic Med. 2003;20:255–68.PubMedCrossRef
38.
Zurück zum Zitat Sjoholm A, Nystrom T. Endothelial inflammation in insulin resistance. Lancet. 2005;365:610–2.PubMed Sjoholm A, Nystrom T. Endothelial inflammation in insulin resistance. Lancet. 2005;365:610–2.PubMed
39.
Zurück zum Zitat Lyon CJ, Law RE, Hsueh WA. Adiposity, inflammation and atherogenesis. Endocrinology. 2003;144:2195–200.PubMedCrossRef Lyon CJ, Law RE, Hsueh WA. Adiposity, inflammation and atherogenesis. Endocrinology. 2003;144:2195–200.PubMedCrossRef
40.
Zurück zum Zitat Saenz A, Fernandez-Esteban I, Mataix A et al. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews, 2005, CD002966. Saenz A, Fernandez-Esteban I, Mataix A et al. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews, 2005, CD002966.
41.
Zurück zum Zitat Schafers RF. Do effects on blood pressure contribute to improved clinical outcomes with metformin? Diabetes Metab. 2003;29:62–70. Schafers RF. Do effects on blood pressure contribute to improved clinical outcomes with metformin? Diabetes Metab. 2003;29:62–70.
42.
Zurück zum Zitat Wulffele MG, Kooy A, de Zeeuw D, et al. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med. 2004;256:1–14.PubMedCrossRef Wulffele MG, Kooy A, de Zeeuw D, et al. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med. 2004;256:1–14.PubMedCrossRef
43.
Zurück zum Zitat Lawrence JM, Reid J, Taylor GJ, et al. Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes. Diabetes Care. 2004;27:41–6.PubMedCrossRef Lawrence JM, Reid J, Taylor GJ, et al. Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes. Diabetes Care. 2004;27:41–6.PubMedCrossRef
44.
Zurück zum Zitat Ohira M, Miyashita Y, Ebisuno M, et al. Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients. Diabetes Res Clin Pract. 2007;78:34–41.PubMedCrossRef Ohira M, Miyashita Y, Ebisuno M, et al. Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients. Diabetes Res Clin Pract. 2007;78:34–41.PubMedCrossRef
45.
Zurück zum Zitat Chu NV, Kong AP, Kim DD, et al. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care. 2002;25:542–9.PubMedCrossRef Chu NV, Kong AP, Kim DD, et al. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care. 2002;25:542–9.PubMedCrossRef
46.
Zurück zum Zitat Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001;37:1344–50.PubMedCrossRef Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001;37:1344–50.PubMedCrossRef
47.
Zurück zum Zitat De Aguiar LG, Bahia LR, Villela N, et al. Metformin improves endothelial vascular reactivity in first degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance. Diabetes Care. 2006;29:1083–9.PubMedCrossRef De Aguiar LG, Bahia LR, Villela N, et al. Metformin improves endothelial vascular reactivity in first degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance. Diabetes Care. 2006;29:1083–9.PubMedCrossRef
48.
Zurück zum Zitat Vitale C, Mercuro G, Cornoldi F, et al. Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med. 2005;258:250–6.PubMedCrossRef Vitale C, Mercuro G, Cornoldi F, et al. Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med. 2005;258:250–6.PubMedCrossRef
49.
Zurück zum Zitat Marfella R, Acampora R, Verrazzo G, et al. Metformin improves hemodynamic and fheological responses to L-arginine in NIDDM patients. Diabetes Care. 1996;19:934–9.PubMedCrossRef Marfella R, Acampora R, Verrazzo G, et al. Metformin improves hemodynamic and fheological responses to L-arginine in NIDDM patients. Diabetes Care. 1996;19:934–9.PubMedCrossRef
50.
Zurück zum Zitat Asagami T, Abbasi F, Stuelinger M, et al. Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism. 2002;51:843–6.PubMedCrossRef Asagami T, Abbasi F, Stuelinger M, et al. Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism. 2002;51:843–6.PubMedCrossRef
51.
Zurück zum Zitat Natale A, Baldeweg S, Toschi E, et al. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care. 2004;27:1349–57.CrossRef Natale A, Baldeweg S, Toschi E, et al. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care. 2004;27:1349–57.CrossRef
52.
Zurück zum Zitat Kautzky-Willer A, ra A, Winzer C, et al. Insulin sensitivity during oral glucose tolerance test and its relation to parameters of glucose metabolism and endothelial function in type 2 diabetes subjects under metformin of thiazolidinedione. Diab Obesity Metab. 2006;8:561–7.CrossRef Kautzky-Willer A, ra A, Winzer C, et al. Insulin sensitivity during oral glucose tolerance test and its relation to parameters of glucose metabolism and endothelial function in type 2 diabetes subjects under metformin of thiazolidinedione. Diab Obesity Metab. 2006;8:561–7.CrossRef
53.
Zurück zum Zitat Carantoni M, Abbasi F, Chu L, et al. Adherence of mononuclear cells to endothelium in vitro is increased in NIDDM. Diabetes Care. 1997;20:1462–6.PubMedCrossRef Carantoni M, Abbasi F, Chu L, et al. Adherence of mononuclear cells to endothelium in vitro is increased in NIDDM. Diabetes Care. 1997;20:1462–6.PubMedCrossRef
54.
Zurück zum Zitat Mamputu JC, Wiernsperger N, Renier G. Metformin inhibits monocyte adhesion to endothelial cells and foam cell formation. Br J Diabetes Vasc Dis. 2003;3:302–10. Mamputu JC, Wiernsperger N, Renier G. Metformin inhibits monocyte adhesion to endothelial cells and foam cell formation. Br J Diabetes Vasc Dis. 2003;3:302–10.
55.
Zurück zum Zitat De Jager J, Kooy A, Lehert P. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized placebo-controlled trial. J Intern Med. 2005;257:100–9.PubMedCrossRef De Jager J, Kooy A, Lehert P. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized placebo-controlled trial. J Intern Med. 2005;257:100–9.PubMedCrossRef
56.
Zurück zum Zitat Skrha J, Praznv M, Milgertova J, et al. Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus. Eur J Clin Pharmacol. 2007;63:1107–14.PubMedCrossRef Skrha J, Praznv M, Milgertova J, et al. Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus. Eur J Clin Pharmacol. 2007;63:1107–14.PubMedCrossRef
58.
Zurück zum Zitat Carter AM, Bennett CE, Bostock JA, Grant PJ. Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with type 2 diabetes mellitus. Diabetic Med. 2005;22:1282–4.PubMedCrossRef Carter AM, Bennett CE, Bostock JA, Grant PJ. Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with type 2 diabetes mellitus. Diabetic Med. 2005;22:1282–4.PubMedCrossRef
59.
Zurück zum Zitat Akbar DH. Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome. Endocrine. 2005;20:215–8.CrossRef Akbar DH. Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome. Endocrine. 2005;20:215–8.CrossRef
60.
Zurück zum Zitat Morin-Papunen L, Rautio K, Ruokonen A, et al. Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:4649–54.PubMedCrossRef Morin-Papunen L, Rautio K, Ruokonen A, et al. Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:4649–54.PubMedCrossRef
61.
Zurück zum Zitat Caballero AE, Degado A, Aguillar-Salinas CA, 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.PubMedCrossRef Caballero AE, Degado A, Aguillar-Salinas CA, 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.PubMedCrossRef
62.
Zurück zum Zitat Hattori Y, Suzuki K, Hattori S, et al. Metformin inhibits cytokine-induced nuclear factor kappa B activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension. 2006;47:1183–8.PubMedCrossRef Hattori Y, Suzuki K, Hattori S, et al. Metformin inhibits cytokine-induced nuclear factor kappa B activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension. 2006;47:1183–8.PubMedCrossRef
63.
Zurück zum Zitat Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605.PubMedCrossRef Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605.PubMedCrossRef
64.
Zurück zum Zitat Meifen C, Jie X, Linuo Z, et al. Nonenzymatical glycation of protein in vitro and its inhibition by aminoguanidine or metformin. Acta Acad Med Shanghai. 1998;25:35–8. Meifen C, Jie X, Linuo Z, et al. Nonenzymatical glycation of protein in vitro and its inhibition by aminoguanidine or metformin. Acta Acad Med Shanghai. 1998;25:35–8.
65.
Zurück zum Zitat Beisswenger P, Howell S, Touchette A, et al. Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes. 1999;48:198–202.PubMedCrossRef Beisswenger P, Howell S, Touchette A, et al. Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes. 1999;48:198–202.PubMedCrossRef
66.
Zurück zum Zitat Wiernsperger NF. 50 years later: is metformin a vascular drug with antidiabetic properties? Br J Diabetes Vasc Dis. 2007;7:204–10.CrossRef Wiernsperger NF. 50 years later: is metformin a vascular drug with antidiabetic properties? Br J Diabetes Vasc Dis. 2007;7:204–10.CrossRef
67.
Zurück zum Zitat Pavlovic D, Kocic R, Kocic G, et al. Effect of four-week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes. Diabetes Obesity Metab. 2000;2:251–6.CrossRef Pavlovic D, Kocic R, Kocic G, et al. Effect of four-week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes. Diabetes Obesity Metab. 2000;2:251–6.CrossRef
68.
Zurück zum Zitat Ouslimani N, Peynet J, Bonnefont-Rousselot D, et al. Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells. Metabolism. 2005;54:829–34.PubMedCrossRef Ouslimani N, Peynet J, Bonnefont-Rousselot D, et al. Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells. Metabolism. 2005;54:829–34.PubMedCrossRef
69.
Zurück zum Zitat Mahrouf M, Ouslimani N, Peynet J, et al. Metformin reduces angiotensin-mediated intracellular production of reactive oxygen species in endothelial cells through the inhibition of protein kinase C. Biochem Pharmacol. 2006;72:176–83.PubMedCrossRef Mahrouf M, Ouslimani N, Peynet J, et al. Metformin reduces angiotensin-mediated intracellular production of reactive oxygen species in endothelial cells through the inhibition of protein kinase C. Biochem Pharmacol. 2006;72:176–83.PubMedCrossRef
70.
Zurück zum Zitat Onaran I, Guven GS, Ozdas SB, et al. Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress. Mutation Res. 2006;611:1–8.PubMed Onaran I, Guven GS, Ozdas SB, et al. Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress. Mutation Res. 2006;611:1–8.PubMed
71.
Zurück zum Zitat Gargiulo P, Caccese D, Pignatelli P, et al. Metformin decreases platelet superoxide anion production in diabetic patients. Diabetes Metabolism Res Revs. 2002;18:156–9.CrossRef Gargiulo P, Caccese D, Pignatelli P, et al. Metformin decreases platelet superoxide anion production in diabetic patients. Diabetes Metabolism Res Revs. 2002;18:156–9.CrossRef
72.
Zurück zum Zitat Tessier D, Maheux P, Khalil A, Fulop T. Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Metabolism. 1999;48:897–903.PubMedCrossRef Tessier D, Maheux P, Khalil A, Fulop T. Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Metabolism. 1999;48:897–903.PubMedCrossRef
73.
Zurück zum Zitat Wiernsperger NF. Metformin: intrinsic vasculoprotective properties. Diabetes Technol Therap. 2000;2:259–72.CrossRef Wiernsperger NF. Metformin: intrinsic vasculoprotective properties. Diabetes Technol Therap. 2000;2:259–72.CrossRef
74.
Zurück zum Zitat Mamputu JC, Wiernsperger NF, Renier G. Antiatherogenic properties of metformin: the experimental evidence. Diabetes Metab. 2003;29:6S71–76.PubMedCrossRef Mamputu JC, Wiernsperger NF, Renier G. Antiatherogenic properties of metformin: the experimental evidence. Diabetes Metab. 2003;29:6S71–76.PubMedCrossRef
75.
Zurück zum Zitat Marquie G. Effect of metformin on lipid metabolism in the rabbit aortic wall. Atherosclerosis. 1978;30:165–70.PubMedCrossRef Marquie G. Effect of metformin on lipid metabolism in the rabbit aortic wall. Atherosclerosis. 1978;30:165–70.PubMedCrossRef
76.
Zurück zum Zitat Marquie G. Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits. Atherosclerosis. 1983;47:7–17.PubMedCrossRef Marquie G. Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits. Atherosclerosis. 1983;47:7–17.PubMedCrossRef
77.
Zurück zum Zitat Chakrabarti R, Hocking ED, Fearnley GR. Fibrinolytic effect of metformin in coronary artery disease. Lancet. 1965;II:256–9.CrossRef Chakrabarti R, Hocking ED, Fearnley GR. Fibrinolytic effect of metformin in coronary artery disease. Lancet. 1965;II:256–9.CrossRef
78.
Zurück zum Zitat Hocking ED, Chakrabarti R, Evans J, Fearnley GR. Effects of biguanides and atromid on fibrinolysis. J Atheroscl Res. 1967;7:121–30. Hocking ED, Chakrabarti R, Evans J, Fearnley GR. Effects of biguanides and atromid on fibrinolysis. J Atheroscl Res. 1967;7:121–30.
79.
Zurück zum Zitat Vague PH, Juhan-Vague I, Alessi MC, et al. Metformin decreases the high plasminogen activation inhibitor activity, plasma insulin and triglyceride levels in non-diabetic obese subjects. Thromb Haemostasis. 1987;57:326–8. Vague PH, Juhan-Vague I, Alessi MC, et al. Metformin decreases the high plasminogen activation inhibitor activity, plasma insulin and triglyceride levels in non-diabetic obese subjects. Thromb Haemostasis. 1987;57:326–8.
80.
Zurück zum Zitat Grant PJ, Strickl;and MH, Booth NA, Prentice CRM. Metformin causes a reduction in basal and post-venous occlusion plasminogen activator inhibitor-1 in type 2 diabetic patients. Diabetic Med. 1991;8:361–5.PubMedCrossRef Grant PJ, Strickl;and MH, Booth NA, Prentice CRM. Metformin causes a reduction in basal and post-venous occlusion plasminogen activator inhibitor-1 in type 2 diabetic patients. Diabetic Med. 1991;8:361–5.PubMedCrossRef
81.
Zurück zum Zitat Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care. 1993;16:621–9.PubMedCrossRef Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care. 1993;16:621–9.PubMedCrossRef
82.
Zurück zum Zitat Grant PJ. The effect of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care. 1996;19:64–6.PubMedCrossRef Grant PJ. The effect of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care. 1996;19:64–6.PubMedCrossRef
83.
Zurück zum Zitat Grant PJ. Metformin reduces circulating factor VII concentrations in patients with type 2 diabetes mellitus. Thromb Haemostasis 1998;80:209.CrossRef Grant PJ. Metformin reduces circulating factor VII concentrations in patients with type 2 diabetes mellitus. Thromb Haemostasis 1998;80:209.CrossRef
84.
Zurück zum Zitat He G, Pedersen SB, Bruun JM, et al. Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue. Horm Metab Res. 2003;35:18–23.PubMedCrossRef He G, Pedersen SB, Bruun JM, et al. Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue. Horm Metab Res. 2003;35:18–23.PubMedCrossRef
85.
Zurück zum Zitat Standeven KF, Ariens RAS, Whitaker P, et al. The effect of dimethyl biguanide on thrombin activity FXIII activation, fibrin polymerization and fibrin clot formation. Diabetes. 2002;51:189–97.PubMedCrossRef Standeven KF, Ariens RAS, Whitaker P, et al. The effect of dimethyl biguanide on thrombin activity FXIII activation, fibrin polymerization and fibrin clot formation. Diabetes. 2002;51:189–97.PubMedCrossRef
86.
Zurück zum Zitat Grant PJ. Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003;29:6S44–52.PubMed Grant PJ. Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003;29:6S44–52.PubMed
87.
Zurück zum Zitat Janka HU. Platelet and endothelial function tests during metformin treatment in diabetes mellitus. Horm Metab Res. 1985;12:120–2. Janka HU. Platelet and endothelial function tests during metformin treatment in diabetes mellitus. Horm Metab Res. 1985;12:120–2.
88.
Zurück zum Zitat Gregorio F, Ambrosi F, Manfrini S. Poorly controlled elderly type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin. Diabetic Med. 1999;16:1016–24.PubMedCrossRef Gregorio F, Ambrosi F, Manfrini S. Poorly controlled elderly type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin. Diabetic Med. 1999;16:1016–24.PubMedCrossRef
89.
Zurück zum Zitat Weichert W, Breddin K. Antithrombotic effects of metformin in laser injured arteries. Diabetes Metab. 1988;14:540–43. Weichert W, Breddin K. Antithrombotic effects of metformin in laser injured arteries. Diabetes Metab. 1988;14:540–43.
90.
Zurück zum Zitat Massad L, Plotkine M, Allix M, Boulu RG. Antithrombic drugs in a carotid occlusion model: beneficial effect of the antidiabetic agent metformin. Diabetes Metab. 1988;14:544–48. Massad L, Plotkine M, Allix M, Boulu RG. Antithrombic drugs in a carotid occlusion model: beneficial effect of the antidiabetic agent metformin. Diabetes Metab. 1988;14:544–48.
91.
Zurück zum Zitat Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care. 1995;18:258–68.PubMedCrossRef Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care. 1995;18:258–68.PubMedCrossRef
92.
Zurück zum Zitat Diabetes Control and complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.CrossRef Diabetes Control and complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.CrossRef
93.
Zurück zum Zitat Wiernsperger NF, Bouskela E. Microcirculation in insulin resistance and diabetes: more than just a complication. Diabetes Metab. 2003;29:6S77–87.PubMedCrossRef Wiernsperger NF, Bouskela E. Microcirculation in insulin resistance and diabetes: more than just a complication. Diabetes Metab. 2003;29:6S77–87.PubMedCrossRef
94.
Zurück zum Zitat Tooke JE. Microvascular function in human diabetes: a physiological perspective. Diabetes. 1995;44:721–6.PubMedCrossRef Tooke JE. Microvascular function in human diabetes: a physiological perspective. Diabetes. 1995;44:721–6.PubMedCrossRef
95.
Zurück zum Zitat Stansberry KB, Shapiro SA, Hill MA, et al. Impaired peripheral vasomotion in diabetes. Diabetes Care. 1996;19:715–21.PubMedCrossRef Stansberry KB, Shapiro SA, Hill MA, et al. Impaired peripheral vasomotion in diabetes. Diabetes Care. 1996;19:715–21.PubMedCrossRef
96.
Zurück zum Zitat Sartoretto JL, Melo GA, Carvalho MH, et al. Metformin treatment restores the altered micro-vascular reactivity in neonatal streptozotocin-induced diabetic rats by increasing NOS activity, but not NOS expression. Life Sci. 2005;77:2676–89.PubMedCrossRef Sartoretto JL, Melo GA, Carvalho MH, et al. Metformin treatment restores the altered micro-vascular reactivity in neonatal streptozotocin-induced diabetic rats by increasing NOS activity, but not NOS expression. Life Sci. 2005;77:2676–89.PubMedCrossRef
97.
Zurück zum Zitat Rapin JR, Lespinasse P, Yoa R. Effect of metformin on diabetic erythrocyte deformability in the presence of insulin: in vitro study on erythrocytes from diabetic patients. Diabetes Metab. 1988;14:610–12. Rapin JR, Lespinasse P, Yoa R. Effect of metformin on diabetic erythrocyte deformability in the presence of insulin: in vitro study on erythrocytes from diabetic patients. Diabetes Metab. 1988;14:610–12.
98.
Zurück zum Zitat Valensi P, Behar A, Andre P, et al. The effects of metformin on the capillary permeability to albumin in women patients with cyclic edema. Angiology. 1995;46:401–8.PubMed Valensi P, Behar A, Andre P, et al. The effects of metformin on the capillary permeability to albumin in women patients with cyclic edema. Angiology. 1995;46:401–8.PubMed
99.
Zurück zum Zitat Jyothirmayi GN, Soni BJ, Masurekar M, et al. Effects of metformin on collagen glycation and diastolic dysfunction in diabetic myocardium. J Cardiovasc Pharmacol Therap. 1998;3:319–26.CrossRef Jyothirmayi GN, Soni BJ, Masurekar M, et al. Effects of metformin on collagen glycation and diastolic dysfunction in diabetic myocardium. J Cardiovasc Pharmacol Therap. 1998;3:319–26.CrossRef
Metadaten
Titel
Metformin: Effects on Micro and Macrovascular Complications in Type 2 Diabetes
verfasst von
Clifford J. Bailey
Publikationsdatum
01.06.2008
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 3/2008
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-008-6092-0

Weitere Artikel der Ausgabe 3/2008

Cardiovascular Drugs and Therapy 3/2008 Zur Ausgabe

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.