Linagliptin may be a promising strategy for not only ameliorating hyperglycemia in type 2 diabetic patients, but also protecting against vascular injury by suppressing ICAM-1 and PAI-1 expression through blockade of the deleterious effects of AGE-RAGE axis partly via inhibition of DPP-4 and M6P/IGF-IIR interaction. The gene discussed is DPP4; the disease is type 2 diabetes mellitus.