No abstract

Non-alcoholic fatty liver disease (NAFLD) is a common health problem with a high mortality burden due to its liver-and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). Impaired hepatic fatty acid (FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors (PPARs) are involved in lipid and glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis. These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet, T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

Among the epidemics of modern time, type 2 diabetes mellitus (T2DM) is one of the main contributors to overall morbidity as well as mortality. A number of different treatment options are available for the management of diabetes. Among them thiazolidinediones (TZDs) is an interesting drug class since it does not target the result of T2DM, i.e., hyperglycemia but rather some of the core mechanisms of the disease. Indeed, glitazones increase insulin sensitivity by activating the peroxisome proliferator-activated receptor γ, which plays an important role in regulating various metabolic parameters. Although TZDs have an established efficacy in T2DM treatment, their usage during the past years was questioned following the emergence of some alarming data regarding their safety and especially the cardiovascular safety of rosiglitazone. As a result, there is often some skepticism about the current role of TZDs in T2DM management. This mainly affects rosiglitazone even leading to its withdrawal from several markets in contrast to pioglitazone, which has shown a beneficial cardiovascular profile. A comprehensive assessment of the benefit-to-risk ratio of TZDs is required in order to better understand the place of these drugs in T2DM management.

Summary Background:  Statin treatment may be associated with adverse effects on glucose metabolism. Whether this is a class effect is not known. In contrast, ezetimibe monotherapy may beneficially affect insulin sensitivity. Objective:  The aim of this study was to compare the effects of three different regimens of equivalent low‐density lipoprotein cholesterol (LDL‐C) lowering capacity on glucose metabolism. Methods:  A total of 153 patients (56 men), who had not achieved the LDL‐C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATP III) despite a 3‐month dietary and lifestyle intervention, were randomly allocated to receive open‐label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks. The primary end point was changes in homeostasis model assessment of insulin resistance (HOMA‐IR). Secondary endpoints consisted of changes in fasting insulin levels, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), the HOMA of β‐cell function (HOMA‐B) (a marker of basal insulin secretion by pancreatic β‐cells), LDL‐C and high sensitivity C reactive protein (hsCRP). Results:  At week 12, all three treatment regimens were associated with significant increases in HOMA‐IR and fasting insulin levels (p < 0.05 compared with baseline). No significant difference was observed between groups. No change in FPG, HbA1c and HOMA‐B levels compared with baseline were noted in any of the three treatment groups. Changes in serum lipids and hsCRP were similar across groups. Conclusion:  To the extent that simvastatin 40 mg, rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance, they appear to be of the same magnitude.

Antiplatelet drugs are important components in the management of atherothrombotic vascular disease. However, several limitations restrict the safety and efficacy of current antiplatelet therapy in clinical practice. Interpatient variability and resistance to aspirin and/or clopidogrel has spurred efforts for the development of novel agents. Indeed, several antiplatelet drugs are at various stages of evaluation; those at advanced stage of development are the focus of this review.