The glucagon-like peptide 1 receptor (GLP-1R) is a class B1 G protein coupled receptor (GPCR) that signals primarily through the stimulatory G (Gs) protein. It mediates essential effects of the endogenous peptide GLP-1 in regulating insulin secretion, carbohydrate metabolism and appetite, and thus is an important target for type II diabetes and obesity1. Multiple clinically relevant GLP-1R agonists (GLP-1RAs) have been developed that display a range of signalling profiles2, however, the molecular details that underlie these differences in their mechanism of action is limited by a lack of structural information on how different GLP-1RAs bind to and activate the GLP-1R. In this study, we have determined GLP-1R-Gs complexes bound by different clinically relevant GLP-1RAs including peptides and non-peptide agonists at high resolution (global resolution of 2.1Å-2.5Å) using cryo-electron microscopy (cryo-EM). There is an unexpected overlap between signalling and regulation of the GLP-1R by the non-peptide agonist, PF 06882961, and GLP-1 that was not observed for another compound, CHU-128. Compounds from these patent series, including PF 06882961, are currently in clinical trials for treatment of type 2 diabetes. High resolution cryo-EM structures reveal the binding sites for PF 06882961 and GLP-1 substantially overlap, whereas CHU-128 adopts a unique binding mode with a more open receptor conformation at the extracellular face. Structural differences involving extensive water-mediated hydrogen bond networks could be correlated to functional data to understand how PF 06882961, but not CHU-128, can closely mimic the pharmacological properties of GLP-1. Moreover, analysis of dynamic data present in the cryo-EM micrographs revealed different relative motions within the different GLP-1R agonist complexes. This work provides novel insights into the molecular determinants of GLP-1R ligand binding and receptor activation.