The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) is a class B1 GPCR that is a validated therapeutic target for treatment of metabolic disease including type 2 diabetes and obesity. There is currently major interest in developing next generation peptide and small molecular drugs that target GLP-1R alone, or together with the related gastric inhibitory peptide receptor (GIPR) and/or glucagon receptor (GCGR). We have demonstrated that biased agonism is a common feature of ligands that target the GLP-1R and this may be linked to clinical efficacy. Using single-particle cryo-EM, we have determined structures of different biased agonist ligands in complex with GLP-1 and the Gs heterotrimer that have revealed distinct biased agonists induce distinct receptor conformations and dynamics, providing insights into how differences in biased agonism arise, particular with respect to Gs protein-mediated cAMP vs beta arrestin recruitment. To understand potential relevance of bias in the context of disease we identified mutations in the GLP-1R that biased the signalling of the GLP-1R towards G protein or arrestin pathways. Transgenic mice harbouring these mutations revealed that G protein bias improved metabolic parameters mediated by GLP-1 peptide agonists, while the arrestin-biased GLP-1R mouse had an exacerbated phenotype in diet-induced obesity and were refractory to GLP-1R agonists. These data provide unique insights into GLP-1R biased agonism that will guide future development of novel GLP-1R agonists for treatment of metabolic diseases.