In conclusion, prescription of GLP-1 RA and SGLT2i is strongly recommended to reduce overall CV risk regardless of glycemic control in T2D [142,156,157,158]; however, diabetic patients affected by PAD represent a special setting, which should be considered both the risk of MACE and MALE to choose the best therapeutic strategy in a personalized manner, preferring as first choice GLP-1 RA in those with a prevalent history or risk of lower-limb complications and SGLT2i in those with prevailing heart failure. The gene discussed is GLP1R; the disease is heart failure.