GCG and type 1 diabetes mellitus: Although metformin is claimed to upregulate the synthesis of insulinotropic agents such as glucagon like peptide-1 (GLP-1) through a mechanism requiring PPARα [39] and it was suggested to be well suited for combination with incretin-based therapies [39], there is a majority of reduction in beta cell mass and insulin insufficiency in MLD-STZ induced type 1 diabetic mice, and thus metformin has no effects in glycemic control.