Research Article Details
| Article ID: | A21635 |
| PMID: | 25164277 |
| Source: | Expert Opin Investig Drugs |
| Title: | GFT505 for the treatment of nonalcoholic steatohepatitis and type 2 diabetes. |
| Abstract: | INTRODUCTION: PPARs are nuclear receptors that play key roles in the regulation of metabolism and inflammation. GFT505 is a new dual agonist of the PPARα and PPARδ isoforms, which improves lipid and glucose metabolism in type 2 diabetes mellitus (T2DM) and exerts hepatoprotective effects in mouse models of nonalcoholic fatty liver disease (NAFLD). AREAS COVERED: This evaluation focuses on the pharmacology and clinical activity of GFT505 in metabolic diseases, including T2DM, dyslipidemia and NAFLD, as well as its promise as a therapeutic option for the treatment of nonalcoholic steatohepatitis. Original publications in English were selected, as well as abstracts of presentations in international congresses. Ongoing clinical trials were identified using the Clinicaltrial.gov database. EXPERT OPINION: Results from the completed short-term (4 - 8 weeks) Phase IIa studies indicate that GFT505 decreases plasma triglyceride levels and increases high-density lipoprotein-cholesterol, while lowering low-density lipoprotein-cholesterol in prediabetic patients. Hyperinsulinemic-euglycemic clamp studies have also demonstrated an insulin-sensitizing effect of GFT505, with a strong effect on the liver, with a significant lowering effect on plasma liver enzymes. The current safety profile is reassuring, without any signs of PPARγ-related side effects. The combination of its insulin sensitizing and hepatoprotective effects makes GFT505 an excellent drug candidate for NAFLD. |
| DOI: | 10.1517/13543784.2014.954034 |
| 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 | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D478 | GFT505 | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |