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Metformin - More Than Gold Standard' in The Treatment of Type 2 Diabetes Mellitus
Metformin - More Than Gold Standard' in The Treatment of Type 2 Diabetes Mellitus
Metformin - More Than Gold Standard' in The Treatment of Type 2 Diabetes Mellitus
Čakovec, Croatia
Received: July 22, 2010
Accepted: August 9, 2010
96
A. Marić / METFORMIN – MORE THAN ‘GOLD STANDARD’ IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS
Retrospective and prospective observational studies insulin resistance, such as abdominal obesity,
showed a strong cardioprotective effect of metformin hypertension, hyperinsulinemia, low HDL cholesterol,
in patients with a high prevalence of cardiovascular hypertriglyceridemia and impaired fibrinolysis,
disease, including patients with prior coronary heart resembling the metabolic syndrome (48-50). A meta-
disease events, heart failure, or symptomatic angina analysis of studies comparing metformin with placebo
pectoris (37,38).
or no treatment in women with PCOS showed that
Besides the effects on the classic cardiometabolic metformin significantly reduced fasting plasma
risk factors (dysglycemia, insulin resistance, obesity, glucose, systolic and diastolic blood pressure, LDL
dyslipidemia and high blood pressure) observed in cholesterol and fasting insulin, although total
type 2 DM patients and demonstrated in several cholesterol, HDL cholesterol or triglycerides did not
studies, metformin has other potential anti-
change significantly (51). A Cochrane meta-analysis
atherothrombotic actions. Treatment with metformin
of trials that compared metformin with the oral
improves endothelial function by decreasing
contraceptive pill showed significant improvement in
circulating levels of sVCAM-1 and E-selectin, which
are markers of endothelial activation (39); reduces fasting insulin and triglycerides with metformin, but
circulating levels of plasminogen activator inhibitor-1 no overall improvement in fasting glucose (52).
(40); improves other hemostatic parameters, Besides, both meta-analyses revealed that metformin
decreasing Factor XIII activity and reducing the levels significantly reduced serum testosterone,
of Factor VII, a powerful endogenous promoter of androstenedione and dehydroepiandrostenedione
coagulation (41). Metformin reduces circulating C- sulfate. Many guidelines suggest the use of metformin
reactive protein level (42); inhibits activation of the as initial pharmacological therapy for most women
pro-inflammatory nuclear transcription factor, NF- with PCOS, particularly when overweight or obese
kappaB, secondary to an increase in the activity of the (53), or in addition to clomifene in clomifene-resistant
enzyme AMP-kinase (AMPK), which has been anovulatory women (54). Although metformin crosses
proposed as a cellular mechanism for the anti-
the placenta, observational studies to date suggest that
inflammatory effects of metformin (43). Metformin
metformin does not adversely affect fetal or neonatal
also decreases oxidative stress, inhibits lipid
development (55-57). Metformin used during
peroxidation of LDL and HDL, and the production of
the superoxide free radical (O2-) in platelets (44). pregnancy decreased the risk of gestational diabetes in
Metformin may reduce the production of advanced women with PCOS (58,59).
glycation endproducts (AGE) indirectly, by reduction The mechanisms of metformin effects in PCOS
of hyperglycemia, and directly by an insulin- pertain to its central and peripheral action. At the
independent mechanism (45). Experimental studies
central level, the possible effect is reduction in serum
suggest that metformin may inhibit the binding of
LH level. At the peripheral level, metformin decreases
monocytes to cultured vascular cells, and
hepatic gluconeogenesis, increases the synthesis of sex
differentiation of monocytes into macrophages and
their transformation into foam cells (46). hormone-binding globulin (SHBG), consecutively
decreasing free androgen levels. Metformin also
increases insulin sensitivity in peripheral tissues,
METFORMIN AND POLYCYSTIC OVARY
reduces free fatty acid oxidation, and reduces ovarian
SYNDROME
and adrenal secretion of androgens. Pleiotropic actions
Polycystic ovary syndrome (PCOS) is the most of metformin are mediated by the AMPK pathway.
common endocrine disease in women, affecting 5%- Experimental data show the effect of metformin on the
10% of those in reproductive age (47). PCOS includes expression of some genes involved in glucose
several cardiometabolic risk factors associated with metabolism (60).
98
A. Marić / METFORMIN – MORE THAN ‘GOLD STANDARD’ IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS
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100
A. Marić / METFORMIN – MORE THAN ‘GOLD STANDARD’ IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS
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