Research Article Details
| Article ID: | A31285 |
| PMID: | 30893110 |
| Source: | Curr Opin Lipidol |
| Title: | Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application. |
| Abstract: | PURPOSE OF REVIEW: Several members of the fibroblast growth factor (FGF) family have been identified as key regulators of energy metabolism in rodents and nonhuman primates. Translational studies show that their metabolic actions are largely conserved in humans, which led to the development of various FGF-based drugs, including FGF21-mimetics LY2405319, PF-05231023, and pegbelfermin, and the FGF19-mimetic NGM282. Recently, a number of clinical trials have been published that examined the safety and efficacy of these novel therapeutic proteins in the treatment of obesity, type 2 diabetes (T2D), nonalcoholic steatohepatitis (NASH), and cholestatic liver disease. In this review, we discuss the current understanding of FGFs in metabolic regulation and their clinical potential. RECENT FINDINGS: FGF21-based drugs induce weight loss and improve dyslipidemia in patients with obesity and T2D, and reduce steatosis in patients with NASH. FGF19-based drugs reduce steatosis in patients with NASH, and ameliorate bile acid-induced liver damage in patients with cholestasis. In contrast to their potent antidiabetic effects in rodents and nonhuman primates, FGF-based drugs do not appear to improve glycemia in humans. In addition, various safety concerns, including elevation of low-density lipoprotein cholesterol, modulation of bone homeostasis, and increased blood pressure, have been reported as well. SUMMARY: Clinical trials with FGF-based drugs report beneficial effects in lipid and bile acid metabolism, with clinical improvements in dyslipidemia, steatosis, weight loss, and liver damage. In contrast, glucose-lowering effects, as observed in preclinical models, are currently lacking. |
| DOI: | 10.1097/MOL.0000000000000599 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D005 | Aldafermin | Biological drug | DB16086 | FGF19 analog | Anti-fibrosis | Under clinical trials | Details |
| D046 | Pegbelfermin | Biological drug | DB15365 | FGF21 analog | Improve insulin resistance; Enhance lipid metabolism; Anti-fibrosis | Under clinical trials | Details |