Research Article Details
| Article ID: | A05954 |
| PMID: | 33063664 |
| Source: | Elife |
| Title: | Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver. |
| Abstract: | The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however there is a low conversion rate from success in animals to humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any established therapies and a major field of animal research. We performed a meta-analysis with meta-regression of 603 interventional rodent studies (10,364 animals) in NAFLD to assess which variables influenced treatment response. Weight loss and alleviation of insulin resistance were consistently associated with improvement in NAFLD. Multiple drug classes that do not affect weight in humans caused weight loss in animals. Other study design variables, such as age of animals and dietary composition, influenced the magnitude of treatment effect. Publication bias may have increased effect estimates by 37-79%. These findings help to explain the challenge of reproducibility and translation within the field of metabolism. |
| DOI: | 10.7554/eLife.56573 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |