Metformin: Effects on Micro and Macrovascular Complications in Type 2 Diabetes

Abstract

Metformin has long been known to reduce the development of atherosclerotic lesions in animal models, and clinical studies have shown the drug to reduce surrogate measures such as carotid intima-media thickness. The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity. There may be modest favourable effects against dyslipidaemia, reductions in pro-inflammatory cytokines and monocyte adhesion molecules, and improved glycation status, benefiting endothelial function in the macro- and micro-vasculature. Additionally metformin exerts anti-thrombotic effects, contributing to overall reductions in athero-thrombotic risk in type 2 diabetic patients.

Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin–Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study

“…In the previous report from DIGAMI 2 [17] on the impact of glucose-lowering therapy, it was noted that metformin treatment reduced the number of non-fatal cardiovascular events (myocardial infarction and stroke), albeit at the time, not that of deaths. Continued observation revealed a significantly lower mortality rate in metformin-treated patients, consistent with other observations of cardiovascular benefits of metformin [24,27]. In this context, recent observations by Kooy et al [28] that metformin added to insulin beneficially influenced body weight, glycaemic control and insulin requirement, and also reduced the risk of macrovascular events during a follow-up of somewhat more than 4 years are of interest.…”

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

“…In the UKPDS, metformin treatment in obese patients with T2D has been shown to reduce the incidence of cardiovascular end points and mortality in the 10-year follow-up when compared with conventional treatment (8,9). Moreover, in the Danish nationwide study by Schramm et al (31), metformin therapy was associated with lower mortality and cardiovascular risk when compared with the most common insulin secretagogues, in line with new findings by Hong et al (10).…”

“…This result is assumed to be related to metformin's well-known ability to reduce plasma glucose due to increased insulin-stimulated glucose uptake in peripheral tissue, decreased glycogenolysis, and suppressed hepatic gluconeogenesis (8). However, it has also been suggested that the effect of metformin is at least partly independent of its blood glucose-lowering effect (9). This idea is compatible with a recent study that found beneficial effects on cardiovascular outcome in T2D patients with coronary artery disease on metformin compared with glipizide, despite similar effects on HbA 1c (10).…”

Peroxisome Proliferator-activated Receptor γ Coactivator 1β (PGC-1β) Protein Attenuates Vascular Lesion Formation by Inhibition of Chromatin Loading of Minichromosome Maintenance Complex in Smooth Muscle Cells

“…It has been well known for decades that metformin can inhibit vascular complications in type 2 diabetic patients (46,47,57). Many studies also have shown that metformin has significant and diverse anticancer activity and that the administration of metformin prolongs survival (44,54).…”