LY2405319 / Eli Lilly - LARVOL DELTA

Fibroblast Growth Factor 21 in the Diagnosis and Treatment of Metabolic Disorders (ENDO 2024) - "Since native FGF21 has poor pharmacodynamic properties (e.g., short half-life and proteolytic cleavage by proteases), long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been synthesized and tested in clinical trials for the treatment of obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is a predominantly liver-derived peptide hormone regulating energy expenditure and metabolism of lipids and glucose. Serum FGF21 levels are increased in several metabolic disorders including obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is an attractive target for the treatment of these metabolic disorders."

Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Infectious Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Renal Disease • Septic Shock • Type 2 Diabetes Mellitus • FGF21

FGF21 Serum Dynamics are Linked with Hepatectomy Outcomes and its Analogue Enhances Liver Regeneration (IHPBA 2024) - "The clinically trialed FGF21 analogue LY2405319 was evaluated in a major hepatectomy mouse model... In the post-hepatectomy setting, serum FGF21 is a clinically relevant regenerative biomarker, whilst pre-clinically FGF21 enhanced liver regeneration, supporting FGF21 as a therapeutic target in liver pathology and prevention of PHLF. ::"

Critical care • Fibrosis • Hepatology • Immunology • Liver Failure • Oncology • FGF21

Development of muscle weakness in a mouse model of critical illness: does fibroblast growth factor 21 play a role? (PubMed, Skelet Muscle) - "Endogenous FGF21 is not required for sepsis survival, but may partially protect muscle force and may reduce cellular stress in muscle. Exogenous FGF21 supplementation failed to improve muscle force or cellular stress, not supporting the clinical applicability of FGF21 supplementation to protect against muscle weakness during critical illness."

Journal • Preclinical • CNS Disorders • Infectious Disease • Septic Shock • Vascular Neurology • FGF21

Neuroprotective Effects of the FGF21 Analogue LY2405319. (PubMed, J Alzheimers Dis) - "These data identified LY in vitro as an activator of Aβ degrading genes leading to cerebral Aβ load amelioration in early and late AD pathology. Although Aβ plaque reduction by LY failed in vivo, LY may be used as therapeutic agent to treat AD-related neuroinflammation and impaired neuronal integrity."

Journal • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • APOE • FGF21

Effect of Fibroblast Growth Factor 21 on the Development of Atheromatous Plaque and Lipid Metabolic Profiles in an Atherosclerosis-Prone Mouse Model. (PubMed, Int J Mol Sci) - "We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters...Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Immunology • Inflammation • Metabolic Disorders • APOE • CCL2 • FGF

Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application. (PubMed, Curr Opin Lipidol) - "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."

Clinical • Journal • Cholestasis • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus