Can metformin stabilize PCSK9 level in stable coronary artery disease patients treated with statins?

Abstract

Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an important marker of cardiovascular risk and a new target for therapeutic interventions. We aimed to study the influence of metformin on the level of circulating PCSK9 in patients with stable coronary artery disease (SCAD) and type 2 diabetes (T2DM) or metabolic syndrome (MetS), receiving moderate doses of statins used in routine clinical practice. Material and methods The study included 80 patients with T2DM or MetS receiving rosuvastatin for at least three months prior the study. MetS was diagnosed based on the Global Consensus Definition of the International Diabetes Federation (IDF). Serum level of PCSK9 was measured with an ELISA kit. Results Patients with T2DM or MetS, who took part in the research, were divided into 2 groups – those who received metformin prior the main study (21 patients – 1 st group) and patients who did not (59 patients – 2 nd group). Addition of metformin to the 3-month statin therapy of the 2nd group patients, divided into subgroup A ( n = 27) with the addition of metformin and subgroup B ( n = 29) without one, did not significantly affect the level of lipids. However, the level of circulating PCSK9 in subgroup A patients decreased, compared to subgroup B ( p < 0.01). At the same time, ongoing metformin and rosuvastatin therapy in the 1 st group patients was not accompanied by a further decrease of the PCSK9 level. Conclusions The addition of metformin to ongoing rosuvastatin therapy did not significantly affect serum lipid levels, but stabilized the level of circulating PCSK9, compared with the group without metformin treatment.

Clinical characteristics and management of hyperlipoproteinemia in patients with chronic coronary heart disease in Slovakia

“…Oral statins may even improve diseases not commonly associated with statin use such as psoriasis, particularly in patients with severe disease [24]. Further research has also shown that metformin may stabilize PCSK9 levels in patients with CAD treated with statins [25].…”

The effect of beinaglutide on visceral fat and bodyweight in obese type 2 diabetic patients

“…The effects of the active forms of GLP-1 are mediated by a G protein-coupled receptor, GLP-1R, which is expressed in several sites, including enteric and vagal nerves, the stomach, pancreas, intestine, and various regions of the brain [29]. The physiological functions of GLP-1 include insulin secretion stimulation; glucagon secretion inhibition; protecting β-cells through endoplasmic reticulum stress reduction; reduction of food intake; stomach emptying reduction, thereby reducing the postprandial glucose peak; improvements in cardiomyocyte glucose utilisation, cardiac function, and cardiovascular protection [25,30,31]; and appetite suppression at the level of the hypothalamus and the promotion of weight loss [32][33][34]. Additionally, recent evidence suggests that GLP-1 RA may have a direct action (independent of central nervous system (CNS) actions) in the white adipose tissue inducing browning, enhancing lipolytic capacity and mitochondrial biogenesis [35].…”

Metformin alleviates intervertebral disc degeneration by upregulating MMP-1 expression via the KDM6A/SOX9/miR-202-3p/MMP-1 signaling pathway

“…The H3K27me3 family of demethylases contains several key family members, such as KDM7A KDM6A, and KDM6B, all of which can interact with the tri-methyl groups in their targets to specifically overcome certain factors leading to gene repression during tissue differentiation. As a compound frequently used as a nutritional supplement, metformin treatment has been reported to stabilize the level of circulating PCSK9 in stable coronary artery disease (SCAD) patients [5]. And metformin can directly act on the activation of certain key signaling pathways involved in senescence and aging, including the UTX/KDM6A pathway [15].…”