Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

Decreased serum sodium concentration is a rather frequent electrolyte disorder in the elderly population because of the presence of factors contributing to increased antidiuretic hormone, the frequent prescription of drugs associated with hyponatremia and also because of other mechanisms such as the “tea and toast” syndrome. The aim of this review is to present certain challenges in the evaluation and treatment of hyponatremia in the elderly population and provide practical solutions. Hyponatremia in elderly subjects is mainly caused by drugs (more frequently thiazides and antidepressants), the syndrome of inappropriate antidiuretic hormone secretion (SIAD) or endocrinopathies; however, hyponatremia is multifactorial in a significant proportion of patients. Special attention is needed in the elderly population to exclude endocrinopathies as a cause of hyponatremia before establishing the diagnosis of SIAD, which then requires a stepped diagnostic approach to reveal its underlying cause. The treatment of hyponatremia depends on the type of hyponatremia. Special attention is also needed to correct serum sodium levels at the appropriate rate, especially in chronic hyponatremia, in order to avoid the osmotic demyelination syndrome. In conclusion, both the evaluation and the treatment of hyponatremia pose many challenges in the elderly population.

Background:Recent clinical studies showed that lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA 2 activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA 2 could be a marker of sdLDL in human plasma. Methods: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA 2 activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA 2 ). Non-HDL-Lp-PLA 2 activity and mass were calculated by subtracting the HDL-Lp-PLA 2 from total plasma Lp-PLA 2 . Results: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions <0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA 2 mass, total plasma Lp-PLA 2 activity and non-HDL-Lp-PLA 2 activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDLLp-PLA 2 activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non-HDL-Lp-PLA 2 activity and mass, but not Lp-PLA 2 mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL

Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.

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The combination of orlistat and micronised fenofibrate appears to be safe and may further improve metabolic parameters in overweight and obese patients with MetS compared with each monotherapy.