Research Article Details
| Article ID: | A27850 |
| PMID: | 17253544 |
| Source: | Cochrane Database Syst Rev |
| Title: | Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. |
| Abstract: | BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. It is suspected in persons with elevated aminotransferase levels and features of insulin resistance (or metabolic) syndrome. The pathogenesis of NAFLD is not clear and there is no universal treatment. OBJECTIVES: To assess beneficial and harmful effects of drugs improving insulin resistance for NAFLD and/or NASH. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Chinese Biomedical Database until February 2006. SELECTION CRITERIA: We included randomised clinical trials assessing the effects of drugs improving insulin resistance for patients with NAFLD or NASH. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Only three randomised clinical trials could be included. Two of the trials had unclear allocation concealment. None was blinded regarding outcome assessment. In two trials, metformin was associated with significantly higher normalization of serum alanine aminotransferase (OR fixed 2.83, 95% CI 1.27 to 6.31 versus diet and OR fixed 7.75, 95% CI 2.37 to 25.35 versus vitamin E) and improvement of liver echographic response (OR fixed 5.25, 95% CI 1.09 to 25.21). An improvement of fatty infiltration was observed in a limited number of patients undergoing liver biopsy. In the single pioglitazone trial, a statistically significant improvement of NASH histology was demonstrated. AUTHORS' CONCLUSIONS: At present, there is insufficient data to either support or refute the use of drugs improving insulin resistance for patients with NAFLD, although current limited information suggests a favourable role of drugs improving insulin resistance. It is advisable to carry out large randomised trials on this topic employing clinically relevant outcome measures and adequate methodology, including blinded outcome assessment. |
| DOI: | 10.1002/14651858.CD005166.pub2 |
| 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 |
| 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 |
| 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 |
| D388 | Vitamin E | Supplement | DB00163 | NR1I2; ALOX5; DGKA | Anti-inflammatory | 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 |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | 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 |