RAGE 229 is an antagonist of the interaction between the cytoplasmic tail of the receptor for advanced glycation end products (ctRAGE) and the formin, Diaphanous-1 (DIAPH1) (KD for binding to ctRAGE = 2 nM). RAGE 229 inhibits the migration of human aortic smooth muscle cells in an in vitro wound healing assay (IC50 = 120 nM). RAGE 229 reduces short- and long-term complications of diabetes in mouse models, without lowering blood glucose concentrations. RAGE 229 also reduces plasma concentrations of TNF-α, IL-6, and CCL2/JE-MCP1 and attenuates inflammatory signaling in diabetic mice.