Research Article Details
| Article ID: | A37963 |
| PMID: | 12663234 |
| Source: | J Hepatol |
| Title: | Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis. |
| Abstract: | BACKGROUND/AIMS: Hyperinsulinemia may cause hepatic steatosis and non-alcoholic steatohepatitis (NASH). The aims of this pilot study were to examine the safety of using the insulin-sensitizing peroxisomal proliferator activated receptor (PPAR) gamma ligand rosiglitazone in patients with NASH and determine whether improved insulin sensitivity correlates with improved fatty liver. METHODS: Thirty subjects with NASH and elevated alanine aminotransferase (ALT) levels received rosiglitazone, 4 mg twice daily for 48 weeks; the preliminary results presented here were obtained at 24 weeks. Insulin sensitivity was measured using fasting insulin and glucose levels and liver fat content was estimated by CT imaging. RESULTS: By 24 weeks, rosiglitazone improved insulin sensitivity and reduced liver fat content. The mean ALT decreased from 86 to 37 U/l (P<0.01). Four subjects (13%) withdrew, one because of a rise in ALT from 59 to 277 U/l that coincided with concomitant prednisone use. Subjects experienced a mean weight gain of 3.5% and hemoglobin drop of 1.1 g/dl. CONCLUSIONS: Treatment of NASH with rosiglitazone for 24 weeks improved insulin sensitivity, reduced liver fat content and improved biochemical evidence of hepatocellular injury. These preliminary data provide evidence that hyperinsulinemia may be a cause of NASH. Strategies to improve insulin sensitivity as a treatment of NASH deserve further investigation. |
| DOI: | 10.1016/s0168-8278(03)00027-8 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | 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 |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D311 | Rosiglitazone | Chemical drug | DB00412 | PPARG agonist; PPARA; PPARD | Improve insulin resistance | Failed in clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | 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 |