Research Article Details
| Article ID: | A27577 |
| PMID: | 17935056 |
| Source: | Diab Vasc Dis Res |
| Title: | The role of fenofibrate in clinical practice. |
| Abstract: | Clinical guidelines highlight the importance of dyslipidaemia management for reducing the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome. While statins represent the main focus of therapy, there is increasing evidence that the addition of a fibrate such as fenofibrate provides further reduction in risk. Fenofibrate also offers a number of benefits beyond lipid modification; these are mediated by peroxisome proliferator-activated receptor-alpha (PPARalpha) activation and appear to be independent of effects of glucose and lipid metabolism. Furthermore, as shown by the Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study, fenofibrate treatment has promising effects in preventing progression of diabetes-related microvascular complications. PPARalpha is critical to lipid metabolism in the liver. Recent findings which showed that pioglitazone, a PPARgamma agonist with weak PPARalpha activity, improved fatty liver disease in patients with non-alcoholic steatohepatitis (NASH) and metabolic syndrome or type 2 diabetes have prompted interest in whether more potent PPARalpha agonists, such as fenofibrate, may have a role in the management of non-alcoholic fatty liver disease (NAFLD). The combination of fenofibrate and a statin is well tolerated, with no apparent increase in the risk of myopathy, unlike gemfibrozil-statin combination therapy. In overview, the available evidence indicates that the combination of fenofibrate with a statin is a useful approach for optimising reduction in the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome, as well as delaying the progression of diabetes-related microvascular complications. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of this approach. |
| DOI: | 10.3132/dvdr.2007.053 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | 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 | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D133 | Fenofibrate | Chemical drug | DB01039 | PPARA agonist; NR1I2 partial agonist | Anti-inflammatory | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D406 | Gemfibrozil | Chemical drug | DB01241 | PPARA agonist; SLCO1B1 inhibitor; SLC22A8 inhibitor; SLCO2B1 inhibitor; SLCO1B3 inhibitor | Hypolipidemic drug | Under investigation | Details |
| D349 | Statins | Miscellany | -- | -- | -- | Under clinical trials | Details |