The effects of metformin administration on liver enzymes and body composition in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis: An up-to date systematic review and meta-analysis of randomized controlled trials

Jalali, Mohammad; Rahimlou, Mehran; Mahmoodi, Marzieh; Moosavian, Seyedeh Parisa; Symonds, Michael; Jalali, Ronak; Zare, Morteza; Imanieh, Mohammad Hadi; Stasi, Cristina

doi:10.1016/j.phrs.2020.104799

Cited by 36 publications

(26 citation statements)

References 44 publications

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“…Clinical trials of commonly used drugs such as metformin, pioglitazone and statins have shown benefit on liver biochemistry or histological changes in patients with non-alcoholic steatohepatitis [ 84 , 85 , 86 ]. Benefits are mainly mediated by a reduction in insulin resistance, a mechanism that is not a strong contributor to alcohol-related liver disease.…”

Section: Research Priorities and Future Perspectivesmentioning

confidence: 99%

Alcohol’s Impact on the Gut and Liver

2021

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Alcohol is inextricably linked with the digestive system. It is absorbed through the gut and metabolised by hepatocytes within the liver. Excessive alcohol use results in alterations to the gut microbiome and gut epithelial integrity. It contributes to important micronutrient deficiencies including short-chain fatty acids and trace elements that can influence immune function and lead to liver damage. In some people, long-term alcohol misuse results in liver disease progressing from fatty liver to cirrhosis and hepatocellular carcinoma, and results in over half of all deaths from chronic liver disease, over half a million globally per year. In this review, we will describe the effect of alcohol on the gut, the gut microbiome and liver function and structure, with a specific focus on micronutrients and areas for future research.

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Section: Research Priorities and Future Perspectivesmentioning

confidence: 99%

Alcohol’s Impact on the Gut and Liver

2021

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“…Excessive fat accumulation in the liver causes problems in the regulation of fat metabolism and leads to inflammation [ 15 , 16 ]. In addition, the pathological signal cascade can induce inflammatory factors and apoptosis of damaged cells [ 14 ]. The increasing inflammatory signaling system is closely related to the signal transduction system associated with cardiovascular diseases such as abnormal vasocontraction, endothelial cell loss, and proliferation of vascular smooth muscle cells [ 17 , 18 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mice were divided into four groups ( n = 40): untreated group (UN; normal condition); high-fat diet group (HF; negative control); high-fat diet and treated with metformin (ME; 17 mg/kg/ 100uL/ daily) group (HF + Me; positive control); and high-fat diet and treated with GF (28 mg/kg/ 100uL/ daily) group (HF + GF; test group). Although metformin is not a direct inhibitor of NAFLD, we used it as a reference drug because it is effective in suppressing insulin resistance and is clinically adopted in non-alcoholic fatty liver [ 14 ]. The UN group was treated with 100 μL of normal saline and a normal diet.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological systemic analysis of gardenia fructus against non-alcoholic fatty liver disease and validation of animal models

Lee¹,

Kim

Yoon³

et al. 2022

Phys Act Nutr

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[Purpose] We aimed to investigate the systemic pharmacological analysis of gardenia fructus (GF) and the proof of concepts. We examined the antioxidant and anti-inflammatory effects in high-fat (HF) diet mice.[Methods] The active compounds of GF and the target genes were identified using the Traditional Chinese Medicine Database and Analysis Platform (oral bioavailability ≥ 30%, Caco-2 permeability ≥ -0.4, and drug-likeness ≥ 0.18). The rats were divided into four groups: untreated group, HF group, HF and metformin (17 mg/kg) treated group, and HF and treated with GF (28 mg/kg) for 8 weeks group. Hepatic lesion changes and markers were analyzed using hematoxylin and eosin staining and immunohistochemistry assay.[Results] In the systemic analysis, we identified 14 active compounds including A, B, and C. From these 14 compounds, 242 biological target genes were identified. The top 10 Gene Ontology were analyzed using GO-biological process analysis: removal of superoxide radicals, regulation of endothelial cell apoptotic process, and cellular response to lipopolysaccharide. GF extracts in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mice models significantly regulated hepatic lesion markers, such as mTOR, 8-Hydroxy- 2'-deoxyguanosine as well as oxidative stress activities, TGF-β, and phosphorylation of ERK1/2.[Conclusion] These results suggest that GF, as an exercise supplement, can alleviate NAFLD disease or fatty liver inflammation. Further studies are required to verify the synergistic effect of GF treatment combined with exercise, which is known to alleviate NAFLD and fatty liver inflammation.

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“…The biguanide analogue metformin is a well-known first line treatment for type 2 diabetes mellitus. It also has beneficial effects in other diseases such as polycystic ovary syndrome and non-alcoholic fatty liver disease [ 97 , 98 ]. Metformin has been prescribed for decades and generally has a good safety profile, although there are dose-dependent gastrointestinal adverse events, such as nausea, abdominal pain and diarrhea.…”

Section: Drugs Under Investigation In Clinical Trialsmentioning

confidence: 99%

Drugs in Clinical Development to Treat Autosomal Dominant Polycystic Kidney Disease

Bais

Gansevoort

Meijer

2022

Drugs

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Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation that ultimately leads to kidney failure in most patients. Approximately 10% of patients who receive kidney replacement therapy suffer from ADPKD. To date, a vasopressin V2 receptor antagonist (V2RA) is the only drug that has been proven to attenuate disease progression. However, aquaresis-related adverse events limit its widespread use. Data on the renoprotective effects of somatostatin analogues differ largely between studies and medications. This review discusses new drugs that are investigated in clinical trials to treat ADPKD, such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators and micro RNA inhibitors, and drugs already marketed for other indications that are being investigated for off-label use in ADPKD, such as metformin. In addition, potential methods to improve the tolerability of V2RAs are discussed, as well as methods to select patients with (likely) rapid disease progression and issues regarding the translation of preclinical data into clinical practice. Since ADPKD is a complex disease with a high degree of interindividual heterogeneity, and the mechanisms involved in cyst growth also have important functions in various physiological processes, it may prove difficult to develop drugs that target cyst growth without causing major adverse events. This is especially important since long-standing treatment is necessary in this chronic disease. This review therefore also discusses approaches to targeted therapy to minimize systemic side effects. Hopefully, these developments will advance the treatment of ADPKD.

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The effects of metformin administration on liver enzymes and body composition in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis: An up-to date systematic review and meta-analysis of randomized controlled trials

Cited by 36 publications

References 44 publications

Alcohol’s Impact on the Gut and Liver

Alcohol’s Impact on the Gut and Liver

Pharmacological systemic analysis of gardenia fructus against non-alcoholic fatty liver disease and validation of animal models

Drugs in Clinical Development to Treat Autosomal Dominant Polycystic Kidney Disease

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