Both results of CVOT on hospitalization for HF in T2D unfavorable with saxagliptin in SAVOR-TIMI 53 and favorable ones with empagliflozin in EMPA-REG might be explained, at least in part, by their impact on glucagon levels: DPP-4i reduce, and SGLT-2i increase, glucagon levels [57]. This evidence concerns the gene GCG and type 2 diabetes mellitus.