Research Article Details
| Article ID: | A28079 |
| PMID: | 16672828 |
| Source: | J Clin Gastroenterol |
| Title: | Therapy of NAFLD: Insulin Sensitizing Agents. |
| Abstract: | Insulin resistance is an integral part of the underlying pathophysiology in most patients with nonalcoholic fatty liver disease (NAFLD). Insulin-sensitiziting agents are therefore likely to be of key importance in the treatment of this disorder, especially in the histologically more severe form known as nonalcoholic steatohepatitis. Here we have reviewed the current literature on the two major insulin-sensitizing agents that have been studied in patients with NAFLD: the thiazolidinediones (or PPAR-gamma agonists) and metformin, the only available biguanide. Thiazolidinedione administration in human NAFLD has been shown to decrease hepatic fat by several different global measures and to decrease evidence of cellular injury, but it has also been associated with increased peripheral fat and weight gain. In contrast, metformin has been shown to improve biochemical markers without weight gain, but with more variable improvement in histology. Neither agent has been FDA approved for treating NAFLD, but existing studies have provided much hope for incorporating these medications into NAFLD management strategies in selected patients. |
| DOI: | 10.1097/01.mcg.0000168647.71411.48 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |
| D038 | Biguanide | Chemical drug | DB13100 | -- | -- | 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 |
| 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 |