GLP1R and type 2 diabetes mellitus: While in vitro studies using isolated human intestinal biopsies have suggested that metformin may have a direct effect to induce GLP-1 secretion from enteroendocrine L-cells [28], targeted perfusion of metformin alone to the ileum (where L-cells are densely distributed) failed to induce a meaningful change in plasma GLP-1 levels in patients with T2D [74].