Incretin-based therapies have shown promise in the treatment of type 2 diabetes. Here we review our current understanding of TGR5 as a target to induce glucagon-like peptide-1 (GLP-1) secretion. These new observations suggest that TGR5 agonists may constitute a novel approach to treat type 2 diabetes, as well as complications of diabetes, such as non-alcoholic fatty liver disease.