Berberine is an alkaloid that is highly concentrated in the roots, rhizomes, and stem bark of various plants. It affects glucose metabolism, increasing insulin secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting mitochondrial function, activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine also increases glucose transporter-4 (GLUT-4) and glucagon-like peptide-1 (GLP-1) levels. On GLP-1 receptor activation, adenylyl cyclase is activated, and cyclic adenosine monophosphate is generated, leading to activation of second messenger pathways and closure of adenosine triphosphate-dependent potassium channels. Increased intracellular potassium causes depolarization, and calcium influx through the voltage-dependent calcium channels occurs. This intracellular calcium increase stimulates the migration and exocytosis of the insulin granules. In glucose-consuming tissues, such as adipose, or liver or muscle cells, berberine affects both GLUT-4 and retinol-binding protein-4 in favor of glucose uptake into cells; stimulates glycolysis by AMPK activation; and has effects on the peroxisome proliferator-activated receptor γ molecular targets and on the phosphorylation of insulin receptor substrate-1, finally resulting in decreased insulin resistance. Moreover, recent studies suggest that berberine could have a direct action on carbohydrate metabolism in the intestine. The antidiabetic and insulin-sensitizing effect of berberine has also been confirmed in a few relatively small, short-term clinical trials. The tolerability is high for low dosages, with some gastrointestinal complaints appearing to be associated with use of high dosages.

PCSK9 inhibitors have demonstrated their good safety and tolerability in a large number of subjects with different clinical conditions, including statin-intolerance, enlarging their potential use in a broader range of patients. Further data on long-term mipomersen safety are required.

Metformin is generally recommended as first-line treatment in type 2 diabetes, especially in overweight patients, but in recent years new indications for its use have emerged. Metformin has been found to be safe and efficacious both as monotherapy and in combination with all oral antidiabetic agents and insulins. If metformin use during pregnancy and the lactation period is supported by few data, it could be indicated for women with polycystic ovary syndrome, since it could diminish circulating androgens and insulin resistance, thus ameliorating the ovulation rate. Metformin seems to reduce cancer risk, which appears to be increased in diabetics, and is a promising agent for oncoprevention and chemotherapy combinations. Moreover, metformin could find a place in the treatment of non-alcoholic fatty liver disease. Lactic acidosis could be decreased by avoiding metformin use in patients with hypovolemia, sepsis, renal impairment, hypoxic respiratory diseases and heart failure, in the preoperative period and before intravenous injection of contrast media.

Metabolic syndrome (MetS) is a world-wide epidemic disease associated with increased morbidity and mortality. Treatment strategies include pharmacologic and non-pharmacologic methods, with varying degrees of success rate all over the world. Pharmaceutical interest in this field is growing, together with patients' requests for supplementary (or "alternative") treatments. The knowledge of nutraceuticals beneficial effects in subjects with the MetS could help us to better define the appropriate treatment for these subjects, in particular those with contraindications for commonly used drugs, or to achieve guidelines suggested targets. On the other side, it could be not convenient to use a nutraceutical to treat each metabolic syndrome component (i.e. from 3 to 5) in each affected subjects. Thus, this review tries to focus on widely marketed nutraceuticals with clinically demonstrated effects on more than one component of the MetS, namely omega-3 fatty acids, berberine, psyllium and other soluble fibers, cinnamon, chromium picolinate, banaba, and bitter gourd.

The short-term consumption of a nutraceutical containing isoflavones and berberine was well-tolerated and improved menopausal symptoms, plasma lipid level, and serum levels of matrix metalloproteinases in a cohort of mildly dyslipidemic postmenopausal women when compared with a neutral control.

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Evolocumab is an innovative powerful lipid-lowering drug, additive to statins and with an apparently large therapeutic range associated to a low rate of mild adverse events. If available data will be confirmed in long-term trials with strong outcomes, Evolocumab will provide an essential tool to treat high-risk patients who need to reach ambitious LDL-C target.

Hypertension is one of the most important clinical conditions affecting older people. Its prevalence in this group of subjects is above 60% and continues to grow. Isolated systolic hypertension accounts for the majority of cases as systolic blood pressure increases with advancing age, while diastolic blood pressure remains unchanged or even decreases. Nowadays hypertension is a well established risk factor for stroke and cardiovascular disease among older people and its treatment is considered mandatory. The general recommended blood pressure goal in uncomplicated hypertension is less than 140/90 mmHg, even if this target in older people is based mainly on expert opinion. All patients should receive nonpharmacological treatment, in particular reduction in excess body weight when body mass index is greater than 26 kg/m 2 and dietary salt restriction. Older patients with hypertension may also benefit from smoking cessation, physical activity and alcohol restriction. In relation to drug therapy, a low-dose thiazide diuretic could be a good first step. Other first-line drugs are long-acting calcium channel blockers, generally dihydropyridines, and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The HYVET study showed a specific protective effect of indapamide with or without perindopril in people older than 80 years. Since monotherapy normalizes blood pressure in only 40-50% of cases, a combination of two or more drugs is often required. Moreover the addiction of a second drug may reduce the doserelated adverse effects of the first one. Finally, compliance with treatment should always be achieved by giving complete information to patients and simplifying the drug regimen as much as possible.