Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study

Filippatos, Theodosios D.; Kiortsis, Dimitrios N.; Liberopoulos, Evangelos N.; Georgoula, M.; Mikhailidis, Dimitri P.; Elisaf, Moses

doi:10.1185/030079905x75078

Cited by 88 publications

(76 citation statements)

References 43 publications

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“…In this context, they are commonly used for correcting lipid abnormalities in obese patients with MetS and T2DM [46][47][48] . Their hypolipidemic action is attributed to activation of the peroxisome proliferator-activated receptors (PPAR), particularly PPARα [49] .…”

Section: Introductionmentioning

confidence: 99%

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

129

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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.

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Section: Introductionmentioning

confidence: 99%

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

129

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“…Various classes of drugs have proved useful in the management of patients with type 2 diabetes (T2D) and its complications [1,[5][6][7][8][9][10][11][12]. Recent evidence demonstrated the beneficial effects of incretin-mimetic drugs in the treatment of T2D; these drugs include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors [13,14].…”

Section: Introductionmentioning

confidence: 99%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ 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.

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“…Orlistat has been reported to produce moderate improvements in plasma lipid profiles in obese patients with hypercholesterolaemia [93][94][95] or Metabolic Syndrome [96]. Orlistat is the only antiobesity drug to have been shown to reduce LDL-cholesterol.…”

Section: Dyslipidaemiamentioning

confidence: 99%

Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders

Heal

Gosden

Smith

2009

Brit J Clinical Pharma

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Obesity is a major cause of morbidity and mortality through cardio-and cerebrovascular diseases and cancer. The metabolic consequences of obesity include dyslipidaemia, hypertension, proinflammatory atherogenesis, pre-diabetes and Type 2 diabetes. For a significant proportion of patients, pharmacotherapy to tackle obesity is required as adjunctive support to diet, exercise and lifestyle modification. To this end, the pharmaceutical industry is pursuing many novel drug targets. Although this view is probably not justified, the recent tribulations of rimonabant have created a perception that the regulatory bar for the approval of antiobesity drugs has been raised. Although >5% of placebo-subtracted weight loss maintained over 1 year is the primary efficacy end-point, it is improvements in cardiovascular risk factors that the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) require to grant approval. Safety aspects are also critical in this indication. Many companies are now switching development of their antiobesity drug candidates into other metabolic disorders. Type 2 diabetes is accepted by the industry and FDA, but not EMEA, as the most appropriate alternative. On the other hand, improvements in plasma lipids produced by antiobesity drugs are moderate compared with established therapies, suggesting dyslipidaemia is not a viable development option. Metabolic Syndrome is not accepted by FDA or EMEA as a discrete disease and the agencies will not licence antiobesity drugs for its treatment. The regulatory environment for antiobesity drugs and the spectrum of indications for which they can be approved could change dramatically if positive data for sibutramine emerge from the SCOUT outcome trial.

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Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study

Abstract: 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.

Cited by 88 publications

References 43 publications

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Adverse Effects of GLP-1 Receptor Agonists

Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders

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