GLP-1-GIP-lanifibranor

GLP-1-GIP-lanifibranor (GLP-1-GIP-Lani) is a preclinical unimolecular peptide-drug conjugate designed to treat obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH). Developed by an international collaboration including Helmholtz Munich, the German Center for Diabetes Research (DZD), and Novo Nordisk, the molecule consists of a GLP-1R/GIPR dual agonist peptide backbone covalently linked to lanifibranor, a small-molecule pan-PPAR (α, γ, and δ) agonist. This design utilizes the internalization of GLP-1 and GIP receptors to selectively deliver the PPAR agonist payload into target cells (such as adipocytes, pancreatic beta cells, and specific hypothalamic neurons), thereby achieving localized metabolic rewiring while avoiding the systemic toxicities (e.g., fluid retention, anemia, and weight gain) typically associated with free pan-PPAR agonists. In preclinical mouse models, GLP-1-GIP-lanifibranor demonstrated superior efficacy in reducing body weight, food intake, and hyperglycemia compared to semaglutide or dual incretin therapies.

Other names

GIPR:GLP-1R:PPARα,γ,δ quintuple agonistGLP-1-GIP-LaniGLP1-GIP-LaniGLP 1-GIP-LaniGLP-1:GIP:PanPPAR quintuple agonistGLP-1R/GIPR/Pan-PPAR quintuple agonistGLP-1R–GIPR–PPARα/γ/δ quintuple agonistGLP-5GLP5GLP 5unimolecular GLP-1R/GIPR/Pan-PPAR quintuple agonist