Vasculo-Protective Cover: A Novel Action of Metformin
Keywords:
Type 2 diabetes, Oral anti-diabetic drugs, Metformin ,Vasculo-protective effects, Endothelial dysfunctionsAbstract
Type 2 diabetes is associated with multiple changes/complications in the body that affects almost every organ and system. In
the cardiovascular system main pathology lies in the vascular endothelium leading to atherosclerosis and arteriosclerosis.
Different treatment options are available for diabetes including both oral and injectable drugs. Oral drugs have better compliance
like Sulfonylureas, Alpha glucosidase inhibitors, Glitazones and Maglitinides. These groups of anti-hyperglycemic drugs
maintain blood glucose level, providing diabetics cost effective better life through a physiological route. However, it has been
documented that these drugs do not delay vascular complications in diabetic patients. Metformin is the first line oral anti-diabetic
drug from biguanide group used to treat type 2 diabetes mellitus. It is a euglycemic agent which decreases glucose levels and
have additional benefit of decreasing the progression of vascular effects in multiple ways.
References
American Diabetic Association. Diagnosis and classification
of diabetes mellitus. Diabetes care 2004; 27(1):5-10
George B, Cebioglu M, Yeghiazaxyn K. Inadequate diabetic
care: global figures cry for preventive measures
and personalized treatment. EPMA journal 2010; 1:13-8
Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational
diabetes mellitus and its association with Type
diabetes. Diabetic Medicine 2003; 21:103-13
Catalano PM, Tyzbir ED, Wolfe RR, Calles J, Roman
NM, Amini SB et al. Carbohydrate metabolism during
pregnancy in control subjects and women with gestational
diabetes. Am J Physiol 1993; 264: 60–7
Grant P. Beneficial effects of metformin on homeostasis
and vascular function in man. Diabetes Metabolism 200-
; 29( 2) : 6S44-52
Tripathi KD. Insulin, Oral hypoglycemic drugs and glucagon
In: Essentials of Medical Pharmocology; Tripathi
M editor. Chapter 19, sixth edition. Jaypee brothers India
p 255-8
Agular L G, Bahla L , Villela N ,Laflor C ,Sicuro F, Wiernsperger
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(5) :1083-9
Vapaatalo H, Mervaala E. Clinically important factors
influencing endothelial functions .Med Sci Monit 2001
;7(5) :1075-85
Schachinger V, Britten M, Zeiher A M. Prognostic effects
of impact of coronary vasodilators dysfunction on adverse
long term outcome of coronary heart disease. Circulation
;101: 1899-906
Hsuch W A, Quinones M J. Role of endothelial dysfunction
in insulin resistance. Am j Cardiol 2003 ; 92: 10-17
Davignor J, Peter G. Role of endothelial dysfunction in
atherosclerosis. Circulation 2004;109: 27-32 (doi: 10.11
/01.CIR.000131515.03336.f8)
Casey R C, Joyce M, Moore K, Thompson C, Fitzgerald
P, Bouchier-D J. Two weeks treatment with parvostatin
improves ventriculo-vascular dynamics interactions in
young men with type 1 diabetes. Diabetes and vascular
disease research 2007; 4(1):53-61
Natali A ,Baldeweg S, Toschi E, Capaldo B, Barbaro D,
Gastaldelli A et al. Vascular effects of improving metabolic
control with metformin or rosiglitazone in type 2
diabetes. Diabetes care 2004;27(6): 1349-57
Straughan J L .Focus on metformin – a major cardiovascular
medication .Cardiovascular Journal of Africa 2007
;18(5):331-3
Strack T. Metformin: a review. Drugs Today 2008; 44(4):
-14
Nathan DM, Buse J B , Davidson M B, Heine RJ , Holman
R, Sherwin R. Management of hyperglycemia in
type 2 diabetes :a consensus algorithm for the initiation
and adjustment of therapy. Diabetologia 2006;49:1711-21
Ross SA, Marine Elioe J. Incretin agents in Type 2 diabetes.
Canadian family physician 2010; 56(7): 639-48
Rajos LBA, Rajos MB. Metformin: an old but still the
best treatment for treatment for type 2 diabetes. Diabetology
& Metabolism Syndrome 2013; 5:6- 9 (doi: 10.11
/1758-5996-5-6)
Correia S, Carvalho C , Santos MS, Seica R, Oliveira
CR , Moreira P I. Mechanisms of action of metformin
in type 2 diabetes and associated complications: an over
view. Mini Rev Med Chem 2008; 8(13): 1343-54
Ascis-Buturovic B, Kacila M. Effects of basal insulin
analog and metformin on glycemia control and weight
as risk factors for endothelial dysfunction. Bosn J Med
Sci 2008; 8(4): 309-12
Home PD. Impact of the UKPDS. An overview. Diabet
Med 2008;25(2):2-8
Papanas N, Maltezos E, Mikhailidis DP. Metformin:
diamonds forever. Expert Opin Pharmacother 2009; 10
(15): 2395-7
Wiernsperger NF, Bouskela E. Microcirculation in insulin
resistance and diabetes: more then just a complication.
Diabetes and Metabolism 2003; 29 (4): 6577-87
Majithiya JB, Balaraman R. Metformin reduces blood
pressure and restores endothelial function in aorta of
streptozotocin- induced diabetic rats. Life Sci 2006; 78
(22): 2615-24
Xie W, Zhang SD, Ou XP, Yang TL. Protective effects
of metformin on low density lipoprotein –induced endothelial
dysfunction in rats. Nang Fang Yi Ke Da Xue
Xue Bao 2009; 29(5):890-3
Mather KJ, Verma S, Anderson TJ. Improved endothelial
functions with metformin in type 2 diabetes mellitus. J
Am Coll Cardiol 2001;37:1344-50
Jager DJ, Kooy A, Lehert PH, Bets D, Wulffele MG,
Teerlink T et al. Effects of short term treatment on markers
of endothelial function and inflammatory activity
in type 2 diabetes mellitus: a randomized, placebo- controlled
trial. Journal of internal medicine 2005 ; 257:100-
(doi: 10.1111/j.1365-2796.2004.01420.x)
Alvim de Lima LM, Wiernsperger N, Kraemer-Aguiar
LG, Bouskela E. Short –term treatment with metformin
improves the cardiovascular risk profile in first –degree
relatives of subjects with type 2 diabetes mellitus who
have a metabolic syndrome and normal glucose tolerance
without change in C - reactive protein or fibrinogen. Clinics
; 64(5): 415-30
Kooy A, de Jager J, Lehert P, Bets D, Wulffele MG, Donker
A J M et al .Long term effects of metformin on
metabolism and macrovascular disease in patients with
type 2 diabetes mellitus. Arch Intern Med 2009; 169(6)
:616-25
Scapello J H, Howlett HC. Metformin therapy and clinical
uses. Diab Vasc Dis Res 2008.; 5(3): 157-67
Baily CJ. Metformin: Effects on micro and macrovascular
complication in type 2 diabetes. Cardiovasc Drugs Ther
;22: 215-24
Anfossi G, Russo I, Bonomo K, Trovati M. The cardiovascular
effects of metformin: further reasons to consider
in the therapy of type 2 diabetes mellitus. Curr Vasc Pharmacol
; 8(3): 327-37
Vascular–protective effects of metformin. SA Journal
of diabetes and vascular disease 2007 ;4(4): 198-201
Kirpichnikov D, Macfarlane S I, Sower J R. Metformin:
An Update. Ann Intern Med 2002; 137:25-33
Papanas N, Maltezos E .Oral antidiabetic agents: antiatherosclerotic
properties beyond glucose lowering?
Curr Pharm Des 2009;15(27):3179-92
Orio F, Palomba S, Cascella T, De Simon B, Manguso
F, Savastano S et al. Improvement in endothelial structure
and function in young normal –weight women with polycystic
syndrome: Result of a 6- month study. The Journal
of Clinical Endocrinology 2005;90(11):6072-6
Palomba S, Falbao A, Giallauria F, Russo T, Tolino A,
Zullo F et al. Effects of metformin with and without supplementation
with folate on homocysteine levels and
vascular endothelium of women with polycystic ovary
syndrome. Diabetes care 2010 ;33(2): 246-51
Mather K J, Verma S, Anderson TJ. Improved endothelial
functions with metformin in type 2 diabetes mellitus.J
Am Coll Cardiol 2001; 37: 1344-50
Wiernsperger N F. Review: 50 years later: metformin a
vascular drug with anti diabetic properties? The British
Journal of Diabetes and Vascular Diseases 2007; 7(5):
-10
English PJ, Ashcroft A, Patterson M. Metformin prolongs
the postprandial fall in plasma ghrelin concentration in
type 2 diabetes. Diabetes Metab Res Rev 2007; 23: 299-303
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Copyright (c) 2015 Rabia Arshad, Nasim Karim
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