Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivityin patients with type-2 diabetes mellitus: A placebo-controlled pilot trial

alpha-lipoic acid (ALA), a naturally occuring compound and a radical scaven ger was shown to enhance glucose transport and utilization in different exp erimental and animal models. Clinical studies described an increase of insu lin sensitivity after acute and short-term (10 d) parenteral administration of ALA. The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled, multicenter pilot study to determine se e whether oral treatment also improves insulin sensitivity. Seventy-four pa tients with type-2 diabetes were randomized to either placebo (n = 19); or active treatment in various doses of 600 mg once daily (n = 19), twice dail y (1200 mg; n = 18), or thrice daily (1800 mg; n = 18) alpha-lipoic acid. A n isoglycemic glucose-clamp was done on days 0 (pre) and 29 (post). In this explorative study, analysis was done according to the number of subjects s howing an improvement of insulin sensitivity after treatment. Furthermore, the effects of active vs, placebo treatment on insulin sensitivity was comp ared. All four groups were comparable and had a similar degree of hyperglyc emia and insulin sensitivity at baseline. When compared to placebo, signifi cantly more subjects had an increase in insulin-stimulated glucose disposal (MCR) after ALA treatment in each group. As there was no dose effect seen in the three different ol-lipoic acid groups, all subjects receiving ALA we re combined in the "active" group and then compared to placebo. This reveal ed significantly different changes in MCR after treatment (+27% vs, placebo ; p <.01). This placebo-controlled explorative study confirms previous obse rvations of an increase of insulin sensitivity in type-2 diabetes after acu te and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot tria l need to be substantiated by further investigations. (C) 1999 Elsevier Sci ence Inc.