Metformin monotherapy for type 2 diabetes mellitus

Saenz, Antonio; Fernandez-Esteban, Inmaculada; Mataix, Ángel; Segura, Mónica Ausejo; Figuls, Marta Roqué i; Moher, David

doi:10.1002/14651858.cd002966.pub3

Cited by 235 publications

(173 citation statements)

References 115 publications

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“…Other studies have shown similar findings (12,17), yet a Cochrane review in PCOS (16) showed no changes in HDL cholesterol with metformin. This result contrasts with findings in type 2 diabetes, in which HDL cholesterol increases with metformin (20). These observations warrant further exploration but add to mounting evidence that PCOS is distinct from diabetes from both a reproductive and metabolic perspective.…”

Section: Correlations With Change In Rbp4contrasting

confidence: 82%

Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

et al. 2008

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OBJECTIVE -Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating insulin resistance in overweight women with PCOS.RESEARCH DESIGN AND METHODS -At baseline, 38 overweight women (BMI Ͼ27 kg/m 2 ) with PCOS and 17 weight-matched control subjects were compared. Women with PCOS were then randomly assigned to 6 months of a higher-dose oral contraceptive pill (OCP) (35 g ethinyl estradiol/2 mg cyproterone acetate) or metformin (1 g b.i.d.). Outcome measures were insulin resistance (total insulin area under the curve) on an oral glucose tolerance test, RBP4, and metabolic/inflammatory markers.RESULTS -Overweight women with PCOS were more insulin resistant than control subjects, yet RBP4 levels were not different in women with PCOS versus those in control subjects (35.4 Ϯ 4.3 vs. 28.9 Ϯ 3.1 g/ml, P ϭ 0.36). RBP4 correlated with cholesterol and triglycerides but not with insulin resistance. Metformin improved insulin resistance by 35%, whereas the OCP worsened insulin resistance by 33%. However, RBP4 increased nonsignificantly in both groups (43.7 Ϯ 6.3 vs. 42.6 Ϯ 5.5 g/ml, P ϭ 0.92).CONCLUSIONS -Overweight women with PCOS were more insulin resistant than control subjects, but this finding was not reflected by RBP4 levels. RBP4 correlated with lipid levels but not with insulin resistance markers. RBP4 levels did not change when insulin resistance was reduced by metformin or increased by the OCP. These data suggest that RBP4 is not a useful marker of insulin resistance in PCOS but may reflect other metabolic features of this condition.

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Section: Correlations With Change In Rbp4contrasting

confidence: 82%

Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

et al. 2008

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“…Metformin has been shown to prevent cardiovascular complications associated with diabetes and obesity through mechanisms that presumably involve inhibition of adipose tissue lipolysis, reduction of circulating levels of free fatty acids, and inhibition of low density lipoprotein production (23,24). Although metformin has a broad spectrum of effects, inhibition of mitochondrial complex I and activation of 5' adenosine monophosphate-activated protein kinase (AMPK) appear to be major mechanisms of its action (25,26).…”

Section: Introductionmentioning

confidence: 99%

Activation of AMPK Enhances Neutrophil Chemotaxis and Bacterial Killing

Park

Jiang

Tadié

et al. 2013

Mol Med

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An inability of neutrophils to eliminate invading microorganisms is frequently associated with severe infection and may contribute to the high mortality rates associated with sepsis. In the present studies, we examined whether metformin and other 5′ adenosine monophosphate-activated protein kinase (AMPK) activators affect neutrophil motility, phagocytosis and bacterial killing. We found that activation of AMPK enhanced neutrophil chemotaxis in vitro and in vivo, and also counteracted the inhibition of chemotaxis induced by exposure of neutrophils to lipopolysaccharide (LPS). In contrast, small interfering RNA (siRNA)-mediated knockdown of AMPKα1 or blockade of AMPK activation through treatment of neutrophils with the AMPK inhibitor compound C diminished neutrophil chemotaxis. In addition to their effects on chemotaxis, treatment of neutrophils with metformin or aminoimidazole carboxamide ribonucleotide (AICAR) improved phagocytosis and bacterial killing, including more efficient eradication of bacteria in a mouse model of peritonitis-induced sepsis. Immunocytochemistry showed that, in contrast to LPS, metformin or AICAR induced robust actin polymerization and distinct formation of neutrophil leading edges. Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IκBα degradation. The IκB kinase (IKK) inhibitor PS-1145 diminished IκBα degradation and also prevented LPS-induced inhibition of chemotaxis. These results suggest that AMPK activation with clinically approved agents, such as metformin, may facilitate bacterial eradication in sepsis and other inflammatory conditions associated with inhibition of neutrophil activation and chemotaxis. Online address: https://doi.org/www.molmed.org

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“…This meta-analysis demonstrated a benefit for metformin monotherapy across a diverse range of outcomes including glycemic control, weight loss, lipid and blood pressure control, diabetes-related mortality, all-cause mortality, and incidence of myocardial infarction. 9 Since the publication of UKPDS 34, several generations of antiglycemic agents have been developed, and direct comparisons with metformin have been performed both prospectively and retrospectively. The large multicenter Spread-Dimcad trial (2013) trial (2013) randomized patients with T2DM and CAD to either metformin and glipizide for 3 years.…”

Section: Discussionmentioning

confidence: 99%