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

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.