Research Article Details
| Article ID: | A28077 |
| PMID: | 16503761 |
| Source: | Expert Opin Investig Drugs |
| Title: | Recent findings concerning thiazolidinediones in the treatment of diabetes. |
| Abstract: | Thiazolidinediones (TZDs) are peroxisomal proliferator-activated receptor (PPAR)-gamma agonists. They increase insulin action through several mechanisms including: stimulation of the expression of genes that increase fat oxidation and lower plasma free fatty acid levels; increased expression, synthesis and release of adiponectin; and stimulation of adipocyte differentiation resulting in more and smaller fat cells. TZDs lower blood sugar comparably to sulfonylureas and metformin. The clinical use of TZDs is limited due to the long duration of time required before they reach their full blood sugar-lowering action (3-4 months) and adverse effects such as fluid retention, resulting in excessive weight gain and occasionally in peripheral and/or pulmonary oedema and congestive heart failure. Troglitazone, a TZD that has since been removed from the market because of hepatoxicity, has been demonstrated to decrease the progression from normal or impaired glucose tolerance to overt Type 2 diabetes mellitus. Pioglitazone, another TZD, marginally decreased the incidence of cardiovascular complications in patients with Type 2 diabetes mellitus (PROactive trial). Other, as yet, unapproved uses of TZDs include: non-alcoholic fatty liver disease, in which TZDs reduced hepatic fat accumulation and improved liver function tests; polycystic ovary syndrome, where TZDs improved ovulation, hirsutism and endothelial dysfunction; and lipodystrophies, where TZDs increased body fat (marginally) and decrease liver size. Lastly, because PPAR-alpha and -gamma agonists improve atherosclerotic vascular disease and insulin sensitivity, respectively, dual PPAR-alpha/gamma agonists, which are currently undergoing clinical trials, may be useful in treating patients with the metabolic syndrome. |
| DOI: | 10.1517/13543784.15.3.243 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D353 | Sulfonylurea | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D378 | Troglitazone | Chemical drug | DB00197 | PPARG agonist; PPARD; PPARA | Improve insulin resistance | Under investigation | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |