Evaluating the safety of Liptruzet (ezetimibe and atorvastatin): what are the potential benefits beyond low-density lipoprotein cholesterol-lowering effect?

Husain, Nazik Elmalaika; Hassan, Abdallah; Elmadhoun, Wadie M; Ahmed, Mohamed H.

doi:10.1517/14740338.2015.1063613

Cited by 9 publications

(7 citation statements)

References 64 publications

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“…We also evaluated the effects of ezetimibe on NAFLD associated metabolic disorders. Like other researchers, [11][12][13][14][15][16][17][18][19][20][21] we found, regardless of the ethnicity of the patients recruited into the cohort studies and study design, that treatment with ezetimibe is sufficient for decreasing the serum total cholesterol and LDL-C levels in patients with NAFLD. Ezetimibe reduces the total cholesterol and LDL-C level by selectively targeting NPCL-1, which mediates intestinal absorption of luminal cholesterol and counterbalances hepatobiliary excretion of cholesterol.…”

Section: Discussionsupporting

confidence: 82%

“…The anti-steatosis effect of ezetimibe is thought to be based on its dual role in inhibiting intestinal absorption of cholesterol and suppressing delivery of cholesterol to the liver. [18,19,29] Recent studies have shown that ezetimibe efficiently reduces the absorption of dietary and biliary cholesterol in the proximal jejunum and inhibits the transport of serum cholesterol to liver by binding to Niemann-Pick C1-like 1 (NPCL1) sterol transporter in the enterocyte brush border membrane and hepatocyte canalicular membrane. [36,37] In humans, NPCL1 protein is expressed predominantly in the liver and to a lesser extent in the intestine.…”

Section: Discussionmentioning

confidence: 99%

“…A number of recent clinical trials have been conducted to investigate the role of ezetimibe in the treatment of NAFLD, and some benefits have been shown in terms of improving liver aminotransferase level and liver histology and in ameliorating dyslipidemia and insulin resistance in patients with NAFLD. [11][12][13][14][15][16][17][18][19][20] Most of the studies involving Asian populations have been the uncontrolled pilot studies. A recent, randomized, double-blind, placebo-controlled trial showed no beneficial effects of ezetimibe on patients' liver biochemistry or the histologic changes that accompany NASH.…”

Section: Introductionmentioning

confidence: 99%

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Beneficial Effect of Ezetimibe on Cholesterol Metabolism Ameliorates Hepatic Steatosis

Zheng¹,

Wu²,

Zheng³

et al. 2018

EJCBS

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Background and aim: Cholesterol absorption inhibitor ezetimibe is being used to treat nonalcoholic fatty liver disease (NAFLD) and related metabolic comorbidities. However, its specific efficacy remains unclear. Hence, a meta-analysis was undertaken to clarify the effects of ezetimibe on NAFLD and related metabolic comorbidities. Methods: Electronic databases were searched for clinical trials that investigated the effects of ezetimibe on NAFLD and related metabolic comorbidities. The primary outcome of interest was the effect of ezetimibe on liver enzymes and histology. The secondary outcome of interest was the effect of ezetimibe on lipid metabolism and hepatic insulin resistance. Results: The end-of-treatment (vs. baseline) hepatic steatosis grade and NAFLD activity score (NAS) were significantly improved (steatosis grade: weighted mean difference [WMD]: −0.62, 95% CI: −0.96 to −0.27, P = 0.0005; NAS: WMD: −1.00, 95%CI: −1.46 to −0.55, P < 0.0001) without significant improvement in hepatic lobular inflammation, ballooning, or fibrosis. In Asian participants, the end-of-treatment alanine aminotransferase was significantly decreased (WMD: −12.11 IU/L, 95%CI: −23.81 to −0.41 IU/L, P = 0.04). Treatment with ezetimibe significantly reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (TC: WMD: −37.96 mg/dL, 95%CI: −59.52 to −16.40 mg/dL, P = 0.0006; LDL-C: WMD: −35.55 mg/dL, 95%CI: −57.02 to −14.07 mg/dL, P = 0.001) without a significant effect on triglycerides, high-density lipoprotein cholesterol, glycosylated haemoglobin or the homeostasis model of assessment for insulin resistance index. Conclusions: Results of the meta-analysis confirm beneficial effects of ezetimibe on hepatic steatosis and cholesterol metabolism in patients with NAFLD.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Beneficial Effect of Ezetimibe on Cholesterol Metabolism Ameliorates Hepatic Steatosis

Zheng¹,

Wu²,

Zheng³

et al. 2018

EJCBS

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“…These results suggest that ezetimibe can increase lipoprotein assembly in the liver and perhaps in the intestine. Studies in adult patients with NAFLD have shown improvement in hepatic histology but with worsening or no effects on insulin sensitivity [94,95]. Promising results have been demonstrated when ezetimibe has been used in combination with statins [92].…”

Section: Medical Therapymentioning

confidence: 99%

The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease

et al. 2017

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Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a “multiple-hit process” where the first “hit” is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.

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“…13,19,20) In addition, based on these results, combination drugs that contain fixed-doses of ezetimbe and statin (simvastatin, rosuvastatin or atorvastatin) have been developed and used clinically. [21][22][23] These facts indicate the importance of taking account of cholesterol homeostasis in pharmacotherapy for dyslipidemia.…”

Section: Npc1l1 and Dyslipidemiamentioning

confidence: 98%

Associations between Lifestyle-Related Diseases and Transporters Involved in Intestinal Absorption and Biliary Excretion of Cholesterol

Yamanashi

Takada

Suzuki

2018

Biological & Pharmaceutical Bulletin

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Westernization of dietary habits leads to an increase in lipid intake and is thought to be responsible for an increase in patients with dyslipidemia. It is a well-known fact that the impaired cholesterol homeostasis is closely related to the development of various lifestyle-related diseases such as fatty liver, diabetes, and gallstone as well as dyslipidemia leading to atherosclerosis and cardiovascular diseases such as heart attack and stroke. Therefore, appropriate management of cholesterol levels in the body is considered important in prevention and treatments of these lifestyle-related diseases and in addition, molecular mechanisms controlling plasma (and/or hepatic) cholesterol levels have been intensively studied. Due to its hydrophobicity, cholesterol was long believed to pass through cell membranes by passive diffusion. However, recent studies have identified a number of plasma membrane transporters that are responsible for the cellular uptake or efflux of cholesterol and involved in developments of lifestyle-related diseases. In this review, we focus on Niemann-Pick C1 Like 1 (NPC1L1) and a heterodimer of ATP-binding cassette transporter G5 and G8 (ABCG5/G8), both of which are responsible for intestinal cholesterol absorption and biliary cholesterol secretion, and discuss the relationship between these cholesterol transporters and lifestyle-related diseases. In addition, we also discuss the related uncertainties that need to be explored in future studies.

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Evaluating the safety of Liptruzet (ezetimibe and atorvastatin): what are the potential benefits beyond low-density lipoprotein cholesterol-lowering effect?

Cited by 9 publications

References 64 publications

Beneficial Effect of Ezetimibe on Cholesterol Metabolism Ameliorates Hepatic Steatosis

Beneficial Effect of Ezetimibe on Cholesterol Metabolism Ameliorates Hepatic Steatosis

The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease

Associations between Lifestyle-Related Diseases and Transporters Involved in Intestinal Absorption and Biliary Excretion of Cholesterol

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