When compared to add-on DPP4is, adding a GLP-1 RA or SGLT-2i to metformin therapy was linked with a similar risk of HF hospitalization and mortality, alongside a reduced risk of MACE for GLP-1 RA (HR of 0.82 (0.69-0.97)). In contrast, starting therapy with SU and insulin was related to a greater incidence of MACE (1.22 (1.03-1.49) and 1.23 (1.07-1.47) respectively). Insulin has also been linked to an increased risk of all-cause death (2.33 (2.08-2.61)) and hospitalization (1.54 (1.25-1.91)) from heart failure. This evidence concerns the gene GCG and heart failure.