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α-Lipoic acid (LA) is a disulfide compound that is produced in small quantities in cells, and functions naturally as a co-enzyme in the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase mitochondrial enzyme complexes. In pharmacological doses, LA is a multifunctional antioxidant. LA has been used in Germany for over 30 years for the treatment of diabetes-induced neuropathy. In patients with type 2 diabetes, recent studies have reported that intravenous (i.v.) infusion of LA increases insulin-mediated glucose disposal, whereas oral administration of LA has only marginal effects. If the limitations of oral therapy can be overcome, LA could emerge as a safe and effective adjunctive antidiabetic agent with insulin sensitizing activity.