Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction

Expert Opin Investig Drugs. 2024 Dec;33(12):1167-1176. doi: 10.1080/13543784.2024.2441865. Epub 2024 Dec 17.

Abstract

Introduction: Glucagon-like peptide-1 receptor (GLP-1 R) agonists have demonstrated remarkable effectiveness in the treatment of obesity and type 2 diabetes. Although these agents provide beneficial effects for metabolic dysfunction-associated steatohepatitis (MASH) through their glucose-lowering and weight-reducing properties, their efficacy in promoting fibrosis regression remains unproven. Survodutide, an investigational dual agonist that simultaneously targets both the glucagon receptor (GCGR) and GLP-1 R, has emerged as a promising therapeutic candidate for the comprehensive management of obesity and MASH. By engaging these two critical receptors, this drug has the potential to offer a broad spectrum of metabolic benefits, addressing multiple pathogenic mechanisms underlying these interrelated disorders.

Areas covered: This review examines the pharmacological profile, clinical efficacy, and safety data of survodutide derived from phase 1 and 2 clinical trials.

Expert opinion: Survodutide's dual agonism of the GCGR and GLP-1 R may surpass the efficacy of selective GLP-1 R agonists, demonstrating significant potential in resolving MASH and promoting fibrosis regression. The drug is generally well tolerated, with primarily manageable gastrointestinal adverse effects. As survodutide progresses through phase 3 clinical development, its potential to provide a more effective and holistic approach to treating MASH and its comorbidities may significantly improve patient outcomes and quality of life.

Keywords: Metabolic dysfunction-associated steatotic liver disease; diabetes; fibrosis; metabolic disorders, comorbidities; metabolic dysfunction-associated steatohepatitis; obesity; survodutide.

Publication types

  • Review

MeSH terms

  • Animals
  • Chalcones
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Development
  • Fatty Liver* / drug therapy
  • Glucagon-Like Peptide-1 Receptor* / agonists
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Obesity* / drug therapy
  • Propionates
  • Receptors, Glucagon / agonists

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon
  • 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid
  • Hypoglycemic Agents
  • Propionates
  • Chalcones