Table 1.
PPAR agonists, effects, and market status.
| PPAR Agonist | Indications | Effect | Status | Reference |
|---|---|---|---|---|
| PPARα Agonist | ||||
| Elafibranor | Atherogenic dyslipidemia, diabetes, obesity | Increases HDL cholesterol, lowers triglycerides and LDL cholesterol, improves insulin sensitivity | Phase III clinical trials | (100) |
| Lobeglitazone | Diabetes | Reduces blood sugar levels, lowers hemoglobin A1C levels, improves lipid and liver profiles | Approved in South Korea | (101) |
| WY 14,643 | Lipid metabolism, adipogenesis, cell differentiation, inflammation | – | Preclinical | (102) |
| Pemafibrate | Nonalcoholic fatty liver disease, dyslipidemia | Decreases lipid accumulation | Phase III clinical trials | (103) |
| Fenofibrate | Primary hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia | Increases lipolysis and HDL levels, reduces triglyceride levels, cholesterol, and LDL levels | FDA Approved | (104) |
| Gemfibrozil | Hypertriglyceridemia, dyslipidemia | Increases lipoprotein lipase synthesis and HDL levels, decreases apolipoprotein C-III and LDL levels | FDA Approved | (105) |
| Bezafibrate | Hyperlipidemia | Decreases LDL levels, increases HDL levels | Phase IV clinical trials | (106) |
| Omega-3 | Hypertriglyceridemia, myocardial infarction | Decreases PGE2 levels and plasma triglyceride levels | FDA Approved | (107) |
| PPARγ Agonist | ||||
| Rosiglitazone | Diabetes | Increases insulin-sensitivity, anti-inflammation and NFκβ inhibition Adverse effects: fluid retention, congestive heart disease |
Discontinued | (108) |
| Pioglitazone | Diabetes | Increases insulin sensitivity and blood glucose uptake Adverse effects: congestive heart failure, bladder cancer |
Discontinued | (109) |
| Troglitazone | Diabetes | Antioxidant, vasodilator, anticonvulsant, anticoagulant, and platelet aggregation inhibitor Adverse effects: Liver disease |
Discontinued | (110) |
| AS002 | Ulcerative Colitis | – | Preclinical | (98) |
| AMG-131 | Diabetes | Increases insulin sensitivity, decreases blood glucose levels | Phase II clinical trials | (111) |
| PPARδ Agonist | ||||
| Seladelpar | Hyperlipidemia, primary biliary cholangitis | Decreases holestatic pruritus and fatigue | Phase III clinical trials | (112) |
| GW501516 | Dyslipidemia, obesity, cardiovascular diseaase | Regulates fatty acid oxidation | Phase II clinical trials | (113) |
| PPARα/γ Dual Agonist | ||||
| Muraglitazar | Diabetes | Increases HDL, decreases LDL, triglycerides, and cholesterol Adverse effects: increased risk of heart failure |
Discontinued | (114, 115) |
| Tesaglitazar | Atherogenic dyslipidemia, diabetes | Increase insulin sensitivity Adverse effects: fibrosarcoma |
Discontinued | (115, 116) |
| Naveglitazar | Diabetes | Increases insulin sensitivity | Discontinued | (117) |
| Ragaglitazar | Diabetes, dyslipidemia | Decreases cholesterol, triglycerides, blood glucose, and LDL, increases HDL | Discontinued | (118) |
| Farglitazar | Hypoglycemia, hepatic fibrosis | Decreases fibrosis | Discontinued | (119) |
| Imiglitazar | Diabetes | Decreases hypoglycemic activity Adverse effects: hepatotoxicity |
Discontinued | (120) |
| Netoglitazone | Diabetes | Increases insulin sensitivity | Discontinued | (121) |
| Reglitazar | Diabetes | Decreases triglyceride levels, protects against neuropathy | Discontinued | (122) |
| MK0767 | Dyslipidemia, diabetes | Increases insulin sensitivity, decreases cholesterol and triglyceride levels | Discontinued | (123) |
| KRP-297 | Diabetes | Reduces lipid oxidation and plasma glucose | Discontinued | (124) |
| TZD18 | Diabetes | – | Preclinical | (125) |
| Chiglitazar | Dyslipidemia, diabetes | Increases insulin sensitivity | Phase II clinical trials | (126) |
| Aleglitazar | Diabetes, heart disease | Controls lipid and glucose level with minimal side effects | Phase III clinical trials | (115) |
| Saroglitazar | Diabetes, non-alcoholic fatty liver disease | Decreases transaminase levels, regulates lipid metabolism, increases insulin sensitivity | Phase II clinical trials, Approved in India and Mexico |
(127) |
| PPAR Pan Agonist | ||||
| Bavachinin | Metabolic Syndrome | – | Preclinical | (128) |
| Lanifibranor | Nonalcoholic steatohepatitis | Reduces inflammation, fibrosis, and lipid accumulation | Phase II clincal trials | (129) |
| MHY2013 | Diabetes, hyperlipidemia | – | Preclinical | (130) |