Metformin, lipids and atherosclerosis prevention

Jenkins, Alicia J.; Welsh, Paul; Petrie, John R.

doi:10.1097/mol.0000000000000532

Cited by 49 publications

(47 citation statements)

References 56 publications

(39 reference statements)

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“…Hyperlipidemia is an important risk factor for coronary heart disease [75]. For every 1.0 mmol/L increase in LDL, the risk of acute cardiovascular events increases by about 40%.…”

Section: Discussionmentioning

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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“…Hyperlipidemia is an important risk factor for coronary heart disease [75]. For every 1.0 mmol/L increase in LDL, the risk of acute cardiovascular events increases by about 40%.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…Accordingly, further evaluation of the cardiovascular benefits of metformin in randomized trials will be welcome, as called for by expert societies . Another recent review has noted the evidence for diverse potentially cardioprotective effects of metformin in people with and without type 2 diabetes, arising from various antiatherosclerotic mechanisms . These authors echo the call for further rigorous study of the effects of metformin on hard clinical outcomes, including in people without type 2 diabetes at risk of cardiovascular events.…”

Section: Current and Future Perspectivesmentioning

confidence: 99%

“…1 Another recent review has noted the evidence for diverse potentially cardioprotective effects of metformin in people with and without type 2 diabetes, arising from various antiatherosclerotic mechanisms. 140 Dr Salim Mihson Alruba, a leading diabetes physician in Iraq, contributed importantly to the ideas behind this article but sadly passed away before its preparation. We, the authors, acknowledge his contribution, and our thoughts and prayers are with his family.…”

Section: Current and Future Perspectivesmentioning

confidence: 99%

Mechanisms of action of metformin with special reference to cardiovascular protection

Zilov

Abdelaziz

Alshammary

et al. 2019

Diabetes Metabolism Res

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Summary Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin‐stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP‐1 from intestinal L‐cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin‐treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin‐based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

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“…Effects on lipid profiles are modest, but have included reductions in LDL cholesterol and triglycerides . Numerous findings from experimental systems have been described, including direct cellular antiatherogenic effects (on vascular cells and cholesterol‐depositing macrophages), improved microcirculation, reduced oxidative stress (including that associated with deposition of advanced glycation end products [glycoxidation]), reduced markers of inflammation (including in patients with type 1 diabetes in the REMOVAL trial), effects on the immune system, and modulation of the gut microbiome . In addition, a recently published study randomized 37 non‐diabetic patients with heart failure to metformin (mean dose 1450 mg/day) or to placebo for 3 months, in addition to guideline‐driven, maximally tolerated pharmacologic treatment for heart failure .…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

Metformin and cardiorenal outcomes in diabetes: A reappraisal

Petrie

Rossing

Campbell

2020

Diabetes Obesity Metabolism

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The guidance issued to the pharmaceutical industry by the US Food and Drug Administration in 2008 has led to the publication of a series of randomized, controlled cardiovascular outcomes trials with newer therapeutic classes of glucose-lowering medications. Several of these trials, which evaluated the newer therapeutic classes of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, have reported a reduced incidence of major adverse cardiovascular and/or renal outcomes, usually relative to placebo and standard of care. Metformin was the first glucose-lowering agent reported to improve cardiovascular outcomes in the UK Prospective Diabetes Study (UKPDS) and thus became the foundation of standard care. However, as this clinical trial reported more than 20 years ago, differences from current standards of trial design and evaluation complicate comparison of the cardiovascular profiles of older and newer agents. Our article revisits the evidence for cardiovascular protection with metformin and reviews its effects on the kidney. K E Y W O R D Satherosclerotic cardiovascular disease, cardiovascular outcomes, chronic kidney disease, glucose-lowering therapy, metformin

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Metformin, lipids and atherosclerosis prevention

Cited by 49 publications

References 56 publications

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

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

Mechanisms of action of metformin with special reference to cardiovascular protection

Metformin and cardiorenal outcomes in diabetes: A reappraisal

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