Emerging drugs for diabetic foot ulcers.

Diabetic foot ulceration results from factors extrinsic to the foot such as repeated trauma, ischaemia and infection, as well as intrinsic factors that lead to impairment of wound healing. Intrinsic factors are less well understood, but include deficiency of growth factors, changes in extracellular matrix components with excess proteases, reduced fibroblast activity, cellular abnormalities, deficiencies of angiogenesis, nitric oxide abnormalities and hyperglycaemia. The scientific rationale of therapy is to correct both the external factors that cause diabetic foot ulcers and the internal factors that lead to impairment of wound healing. Current research is leading to new therapies that can be divided into the following classes: growth factors, skin substitutes, extracellular matrix proteins, stem cell therapy, gene therapy, protease inhibitors, angiogenesis stimulants, nitric oxide-releasing agents, adenosine agonists, immunostimulants, vasoactive compounds and granulating agents. These therapies should be considered when existing treatments to correct extrinsic factors have failed to heal ulceration in the diabetic foot.