Research Article Details
| Article ID: | A25837 |
| PMID: | 21411114 |
| Source: | Metabolism |
| Title: | Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. |
| Abstract: | Insulin resistance has an important role in the development of nonalcoholic fatty liver disease (NAFLD) and is involved in both pathological processes: hepatic steatosis and atherosclerosis. Therefore, treatment of NAFLD with insulin sensitizers is likely to have a favorable effect toward hepatic steatosis and cardiovascular outcomes. The present study investigated the effect of metformin on arterial properties, metabolic parameters, and liver function in patients with NAFLD. In a randomized, placebo-controlled study, 63 patients with NAFLD were assigned to 1 of 2 groups: Group 1 received daily metformin; group 2 received placebo. Pulse wave velocity (PWV) and augmentation index (AI) were measured using SphygmoCor (version 7.1; AtCor Medical, Sydney, Australia) at baseline and at the end of the 4-month treatment period. Metabolic measures and serum adiponectin levels were determined. Among metformin-treated patients, PWV and AI decreased significantly during the study. Significant declines in fasting glucose, triglyceride, and alkaline phosphatase and a significant increase in high-density lipoprotein cholesterol were observed. Alanine aminotransferase decreased and serum adiponectin increased marginally. In the placebo group, neither PWV nor AI improved significantly during the treatment period. Alanine aminotransferase, aspartate aminotransferase, and adiponectin did not change in the placebo group. Metformin treatment was associated with significant decrease in PWV and AI in NAFLD patients. This beneficial vascular effect was accompanied by an improvement in glucose and lipid metabolism as well as liver enzymes. |
| DOI: | 10.1016/j.metabol.2011.01.011 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |