Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management

Luo, Fei; Das, Avash; Chen, Jingfei; Wu, Panyun; Li, Xiangping; Fang, Zhenfei

doi:10.1186/s12933-019-0860-y

Cited by 131 publications

(97 citation statements)

References 77 publications

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“…Likewise, metformin users may carry a lower mortality risk compared with nonusers when admitted to an ICU, as observed previously in a Danish nationwide registry-based study and by other observational studies [27,47,48]. Preclinical data indicate that metformin is associated with reduced inflammation, thrombosis, and apoptosis [49]. However, randomiaed controlled trials do not provide evidence that metformin affected the mortality rate of critically ill patients, although they are underpowered for this outcome [50][51][52].…”

Section: Discussionmentioning

confidence: 68%

Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Posma

Frøslev

Jespersen

et al. 2020

Ann. Intensive Care

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Background: Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods: This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results: Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2-3.2) in metformin users and 1.6 (1.0-2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion: In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

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Section: Discussionmentioning

confidence: 68%

Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Posma

Frøslev

Jespersen

et al. 2020

Ann. Intensive Care

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“…According to the studies metformin treatment at a dose of 150 mg/kg for 16 weeks significantly reduce serum high-sensitivity Creactive protein (CRP), which is an indicator of chronic inflammation process in the organism. That suggests that metformin indicates anti-inflammatory effect by inhibiting the secretion of pro-inflammatory cytokines [23]. Metformin reduces the size of myocardial infarction and has a beneficial effect on myocardial remodelling after myocardial infarction.…”

Section: 3mentioning

confidence: 99%

Metformin as a medicine decreasing cardiovascular risk in patients suffering from type 2 diabetes mellitus

Wieteska

Kaczyńska

Maj

et al. 2020

J Educ Health Sport

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Almost half of deaths in Poland (approximately 49%) are caused by cardiovascular system diseases. It means that in 2018 it contributed to the death of over two hundred thousand people in our country. Myocardial infarction, stroke and heart failure are the most common of cardiovascular diseases (CVD). The main risk factor for progression of cardiovascular diseases is type 2 diabetes mellitus (T2D). It is estimated that almost 3 million people suffer from T2D in Poland. Metformin is a promising medicine that reduces cardiovascular risk in patients with T2D. It is currently used as the first line drug in patients suffering from T2D. The aim of the presented article is to review current research on the effectiveness of the metformin as a medicine that reduces cardiovascular risk in patients with T2D. Metformin is the oldest and most commonly used medicine that reduces the concentration of glucose in the peripheral blood in patients with T2D. Due to its very good safety profile, low cost and high effectiveness, metformin is used in the first-line treatment for T2D. Recent studies indicate its protective effect by vasodilation, reducing the size of myocardial infarction, inhibiting apoptosis of cardiomyocytes or reducing oxidative stress. Currently, metformin can be seen to have a great potential in the treatment of cardiovascular complications occurring in the course of T2D. Despite the fact that this medicine has been on the market for many years, the studies on its cardio protective effects have been carried out for a relatively short period of time. It is possible that the detailed understanding of all mechanisms of action of metformin will lead to future advances in the treatment of not only T2D, but also cardiovascular and cancer diseases.

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“…The REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL trial) aimed to ameliorate long-term cardiovascular complications in diabetes patients using metformin [26]. In the REMOVAL trial, metformin treatment reduced the progression of atherosclerosis, weight gain, and low-density lipoprotein (LDL)-cholesterol levels [27,28], though the epigenetic effects of the treatment were not specifically measured. In type 2 diabetes, metformin treatment significantly decreased DNA methylation of metformin the transporter genes solute carrier family 22 member 1 (SLC22A1), solute carrier family 22 member 3 (SLC22A3), and solute carrier family 47 (multidrug and toxin extrusion), member 1 (MATE1) in the livers of patients; in the case of SLC22A1 and SLC22A3, reduced methylation was associated with less hyperglycemia and obesity [29].…”

Section: Therapies Targeting Dna Methylation In T1dmentioning

confidence: 99%

Reading between the (Genetic) Lines: How Epigenetics is Unlocking Novel Therapies for Type 1 Diabetes

Akil

Jerman

Yassin

et al. 2020

Cells

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Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well established that genetic and environmental factors contribute to the initiation and progression of T1D, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with T1D pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage T1D.

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Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management

Cited by 131 publications

References 77 publications

Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Metformin as a medicine decreasing cardiovascular risk in patients suffering from type 2 diabetes mellitus

Reading between the (Genetic) Lines: How Epigenetics is Unlocking Novel Therapies for Type 1 Diabetes

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