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The potential function and clinical application of FGF21 in metabolic diseases
Zhiwei Chen1, Lili Yang1, Yang Liu2
1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
As an endocrine hormone, fibroblast growth factor 21 (FGF21) plays a crucial role in regulating lipid, glucose, and energy metabolism. Endogenous FGF21 is generated by multiple cell types but acts on restricted effector tissues, including the brain, adipose tissue, liver, heart, and skeletal muscle. Intervention with FGF21 in rodents or non-human primates has shown significant pharmacological effects on a range of metabolic dysfunctions, including weight loss and improvement of hyperglycemia, hyperlipidemia, insulin resistance, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). Due to the poor pharmacokinetic and biophysical characteristics of native FGF21, long-acting FGF21 analogs and FGF21 receptor agonists have been developed for the treatment of metabolic dysfunction. Clinical trials of several FGF21-based drugs have been performed and shown good safety, tolerance, and efficacy. Here we review the actions of FGF21 and summarize the associated clinical trials in obesity, type 2 diabetes mellitus (T2DM), and NAFLD, to help understand and promote the development of efficient treatment for metabolic diseases via targeting FGF21.
Insights
Fibroblast growth factor 21 (FGF21) regulates metabolism and shows promise for treating obesity and type 2 diabetes. FGF21 analogs are being developed for metabolic dysfunction, with clinical trials demonstrating safety and efficacy.
Area of Science:
- Endocrinology
- Metabolic Disease Research
- Pharmacology
Background:
- Fibroblast growth factor 21 (FGF21) is an endocrine hormone vital for regulating lipid, glucose, and energy metabolism.
- FGF21 acts on key tissues like the brain, liver, and adipose tissue, influencing metabolic health.
- Native FGF21 has limitations, leading to the development of long-acting analogs and receptor agonists.
Purpose of the Study:
- To review the metabolic actions of FGF21.
- To summarize clinical trials of FGF21-based therapies for metabolic diseases.
- To promote the development of FGF21-targeted treatments for obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD).
Main Methods:
- Review of FGF21's physiological roles in metabolism.
- Summary of preclinical studies in rodents and non-human primates.
- Analysis of clinical trial data for FGF21 analogs and agonists.
Main Results:
- FGF21 intervention demonstrates significant effects on weight loss, hyperglycemia, hyperlipidemia, and insulin resistance.
- FGF21-based drugs show good safety, tolerance, and efficacy in clinical trials.
- Therapeutic targeting of FGF21 offers potential for treating metabolic dysfunctions.
Conclusions:
- FGF21 is a key regulator of metabolic homeostasis with therapeutic potential.
- FGF21 analogs and agonists represent a promising class of drugs for metabolic diseases.
- Further development of FGF21-targeting strategies is warranted for effective metabolic disease treatment.
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