In this review, we systematically summarize the existing findings on the role of all human Wnts, their main antagonists (sFRPs and WIF‐1) and coreceptor (LRP6) in the development of T2DM and related complications and discus current main challenges in designing novel therapeutic strategies targeting Wnts for the treatment of these disorders. The gene discussed is LRP6; the disease is type 2 diabetes mellitus.