Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy

Stee, Mariël F. van; Graaf, Albert A. de; Groen, Albert K.

doi:10.1186/s12933-018-0738-4

Cited by 118 publications

(101 citation statements)

References 183 publications

(176 reference statements)

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“…On the other hand, in controlled T2DM our finding partly suggests that hypoglycemic agents inhibit cholesterol biosynthetic pathways that might be the culprit behind reduced TC level. In addition, in line with our finding, previous study reported inhibition of hepatocellular glucose, lipid and cholesterol biosynthetic pathways due to biguanide metformin treatment of T2DM by transcription ally suppressing steroid receptor coactivator 2 and in part activating the AMP-activated protein kinase pathway [30][31][32].…”

Section: Discussionsupporting

confidence: 91%

Glycemic control and its impact on oxidative stress biomarkers in type 2 diabetic patients treated with metformin: a cross-sectional analysis

Lasisi

Adedokun

Oyenike

et al. 2019

Sci Med

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AIMS: Evidence shows that diabetic patients may be predisposed to oxidative stress owing to increased glyco-oxidation and lipid peroxidation processes in consequence of chronic hyperglycemia. However, there is dearth of information whether glycemic control positively affects the antioxidant defense system in type 2 diabetes mellitus (T2DM). We investigated the potential association between glycemic control and oxidative stress biomarkers in controlled and uncontrolled diabetic states. METHODS: After obtaining ethical clearance, we included patients receiving metformin with glycated hemoglobin A1c ˂7.0% (glycemic control); newly diagnosed T2DM patients without glycemic control with hemoglobin A1c ˃7.0%; and apparently healthy normoglycemic individuals. The following biomarkers were determined: fasting glycemia level, malondialdehyde, glutathione peroxidase activity, catalase activity, total antioxidant capacity and total cholesterol level. The comparisons between the groups were made by ANOVA. RESULTS: The participants were 260 in number: 80 with controlled diabetes, 80 uncontrolled and 100 controls. All participants were between 40 and 71 years old. Fasting glycemia level and hemoglobin A1c showed significant reductions (p<0.05) in controlled T2DM against the uncontrolled T2DM group, all the same both were significantly higher (p<0.05) against the controls. Likewise, malondialdehyde levels showed significant elevations (p<0.05) correspondingly in both uncontrolled and controlled T2DM against the controls, accompanied with significant reductions (p<0.05) in the antioxidative enzyme activities (glutathione peroxidase activity and catalase activity) and total antioxidant capacity levels against the controls. In addition, total cholesterol was significantly reduced (p<0.05) in controlled T2DM against both uncontrolled T2DM and controls, respectively. There were significant correlations between hemoglobin A1c and oxidative stress biomarkers (p<0.05). CONCLUSION: There was no remarkable difference in oxidative stress states between glycemic controlled and uncontrolled T2DM, despite differences in their fasting glycemia and glycated hemoglobin levels. Our data, therefore, suggest that chronic hyperglycemia and possibly anti-diabetic medicationmay both equally associate with oxidative stress.

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Section: Discussionsupporting

confidence: 91%

Glycemic control and its impact on oxidative stress biomarkers in type 2 diabetic patients treated with metformin: a cross-sectional analysis

Lasisi

Adedokun

Oyenike

et al. 2019

Sci Med

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“…However, statins (inhibit the gene expression of HMG-CoA reductase, a key enzyme in the mevalonate pathway) used to reduce LDL-cholesterol and the intracellular cholesterol level, and thus oppose ESRRA activity in vivo [53]. Furthermore, statins increase hepatic gluconeogenesis by up-regulating the mRNA expression of PCK1, a gene that is negatively regulated by ESRRA [57][58][59]. Therefore, although statins may have agonist effects in vitro, their net effects in vivo may actually oppose those of ESRRA.…”

Section: Identification Of Potential Esrra Ligandsmentioning

confidence: 99%

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

Tripathi

Yen

Singh

2020

IJMS

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The estrogen-related receptor alpha (ESRRA) is an orphan nuclear receptor (NR) that significantly influences cellular metabolism.ESRRA is predominantly expressed in metabolically-active tissues and regulates the transcription of metabolic genes, including those involved in mitochondrial turnover and autophagy. Although ESRRA activity is well-characterized in several types of cancer, recent reports suggest that it also has an important role in metabolic diseases. This minireview focuses on the regulation of cellular metabolism and function by ESRRA and its potential as a target for the treatment of metabolic disorders.

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“…Recent studies have also found that metformin has a positive effect on cardiovascular protection [8][9][10][11][12]. Metformin also lowers risk factors for cardiovascular disease such as blood fats [13][14][15], body weight and blood pressure. Compared with insulin and/or oral hypoglycemic agents (except metformin), metformin reduces the risk of all-cause mortality and the incidence of cardiovascular disease [16,17], infection, or acidosis.…”

Section: Introductionmentioning

confidence: 99%

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

Han

Xie

Liu

et al. 2019

Cardiovasc Diabetol

264

150

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Background Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Methods Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). Results In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don’t use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = − 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = − 0.02) and LDL (MD = − 0.08). Conclusion Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.

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Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy

Cited by 118 publications

References 183 publications

Glycemic control and its impact on oxidative stress biomarkers in type 2 diabetic patients treated with metformin: a cross-sectional analysis

Glycemic control and its impact on oxidative stress biomarkers in type 2 diabetic patients treated with metformin: a cross-sectional analysis

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

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