GLP1R and diabetes mellitus: Based on the extensive clinical experience of enhancing GLP1R activation for the treatment of diabetes, it can reasonably be concluded that highly desirable properties for new GPCR agonists would include: Gαs- or Gαq-coupled receptor activity on pancreatic beta and delta cells, low receptor activity on alpha cells, high activity on GLP-1-producing L cells and direct central nervous system effects to reduce food intake.