In conclusion, the findings presented here reveal the potent antiobesity and antidiabetic effects that result when GLP-1 is delivered in combination with FGF21 as a long-circulating and long-acting fusion, suggesting that a sustained release formulation of a GLP-1/FGF21 dual agonist may have great potential for the treatment of overweight patients with T2D. Here, GLP1R is linked to type 2 diabetes mellitus.