Glucagon-like peptide-1 receptor(GLP-1R) agonists are widely used for treating type 2 diabetes mellitus(T2DM) because of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-1 and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-1 actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP-1-based therapeutics, an often-ignored fact, is also discussed. Glucagon-like peptide-1 receptor (GLP-1R) agonists are widely used for treating type 2 diabetes mellitus (T2DM) because of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Therefore, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-1 and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-1 actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP- 1-based therapeutics, an often-ignored fact, is also discussed.