Effect of fibrate treatment on liver function tests in patients with the metabolic syndrome

Gandhi, Nirav; Lenton, Richard; Bhartia, Mithun; Abbas, Ahmad; Raju, Jessie; Ramachandran, Sudarshan

doi:10.1186/2193-1801-3-14

Cited by 18 publications

(13 citation statements)

References 43 publications

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“…Risk of skeletal muscle toxicity increases with higher doses of statin, advanced age (> 65 years), hypothyroidism, renal impairment and, depending on the statin used, concomitant use of other drugs [63]. Nevertheless, myopathy presented with muscle pain and elevated CK levels have been reported when ezetimibe has been added to high-dose atorvastatin [64].…”

Section: Ezetimibe Potential Adverse Effectsmentioning

confidence: 98%

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

Husain

Hassan

Elmadhoun

et al. 2015

Expert Opinion on Drug Safety

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The combination of (eze/ator) is proven to be effective in lowering LDL-c. It is not only a safe and effective treatment of hyperlipidemia, but it also reduces inflammatory markers and atherosclerosis. It is not yet clear, however, whether the combination therapy can decrease the risk of diabetes associated with statin administration. Insulin sensitivity is improved by the single administration of ezetimibe, a finding that is documented by several clinical and animal studies. More specifically, ezetimibe has been shown to decrease insulin resistance associated with nonalcoholic fatty liver disease (NAFLD). The effects of combination therapy that have to be explored in future research and clinical trials include whether this combination can be used in the treatment of NAFLD, cholesterol gallstones and portal hypertension.

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Section: Ezetimibe Potential Adverse Effectsmentioning

confidence: 98%

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

Husain

Hassan

Elmadhoun

et al. 2015

Expert Opinion on Drug Safety

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“…Physical exercise and diet control are the main strategies for MS prevention. The clinical agents including antihypertensive drugs, thiazolidinediones, sulfonylureas, statins and fibrates have been used to treat individual MS symptom in single or combination therapy . However, this treatment strategy increased the risk of side effects and drug–drug interactions .…”

Section: Discussionmentioning

confidence: 99%

“…The clinical agents including antihypertensive drugs, thiazolidinediones, sulfonylureas, statins and fibrates have been used to treat individual MS symptom in single or combination therapy. [34] However, this treatment strategy increased the risk of side effects and drug-drug interactions. [1] Besides the action on lipid metabolism, fibrates were effective for improving glucose metabolism and decreasing blood pressure.…”

Section: Discussionmentioning

confidence: 99%

PPARα-independent action against metabolic syndrome development by fibrates is mediated by inhibition of STAT3 signalling

Yang

Lin

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives Metabolic syndrome (MS) is the concurrence of at least three of five medical conditions: obesity, high blood pressure, insulin resistance, high serum triglyceride (TG) and low serum high-density lipoprotein levels. While fibrates are used to treat disorders other than the lowering serum TG, the mechanism by which fibrates decrease MS has not been established. Methods In this study, wild-type and Ppara-null mice fed a medium fat diet (MFD) were administered gemfibrozil and fenofibrate for three months, to explore the effect and action mechanism. Key findings In Ppara-null mice, MFD treatment increased body weight, adipose tissue, serum TG, and impared glucose tolerance. These phenotypes were attenuated in two groups treated with gemfibrozil and fenofibrate. The STAT3 pathway was activated in adipose and hepatic tissues in positive control, and inhibited in groups treated with gemfibrozil and fenofibrate. The above phenotypes and inflammation were not observed in any wild-type group. In 3T3-L1 adipogenic stem cells treated with high-glucose, STAT3 knockdown greatly decreased the number of lipid droplets. Conclusions Low dose of clinical fibrates was effective against MS development independent of PPARα, and this action was mediated by STAT3 signaling inhibition in adipose tissue, and to a lesser extent in hepatic tissues.

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“…Mild elevations in serum aminotransferases are demonstrated in up to 3% of treated patients, but clinically apparent drug‐induced liver injuries are rare. As shown in a prospective registry by the U.S. Drug Induced Liver Injury Network, which enrolled cases between 2004 and 2012, among 1188 cases of drug‐induced liver injury, only 22 were attributed to a statin (0.018%) . With regard to fibrates, it was found that LFT improved with fibrates due to the reduction of fatty acid oxidation and inflammation .…”

Section: Discussionmentioning

confidence: 99%

“…As shown in a prospective registry by the U.S. Drug Induced Liver Injury Network, which enrolled cases between 2004 and 2012, among 1188 cases of drug-induced liver injury, only 22 were attributed to a statin (0.018%). 6 With regard to fibrates, it was found that LFT improved with fibrates due to the reduction of fatty acid oxidation and inflammation. 7 Fenofibrate may very rarely instigate an autoimmune hepatitis-type reaction with resultant ductopenia, chronic hepatitis, and fibrosis, especially when used in combination with statin medications, 8 a situation not encountered in our case.…”

Section: Discussionmentioning

confidence: 99%

Kombiglyze (metformin and saxagliptin)‐induced hepatotoxicity in a patient with non‐alcoholic fatty liver disease

et al. 2018

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A 33‐year‐old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non‐compliant, complaining of “heaviness of head” after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra‐hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2–5:mixed‐type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.

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Effect of fibrate treatment on liver function tests in patients with the metabolic syndrome

Cited by 18 publications

References 43 publications

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

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

PPARα-independent action against metabolic syndrome development by fibrates is mediated by inhibition of STAT3 signalling

Kombiglyze (metformin and saxagliptin)‐induced hepatotoxicity in a patient with non‐alcoholic fatty liver disease

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