A randomised controlled trial of alpha-lipoic acid (ALA) in patients with diabetic peripheral neuropathy did not show benefits in its primary endpoint, although some secondary endpoints did show possible benefits.

There is much interest in use of antioxidants to treat or slow the progression of diabetic neuropathy, although most trials have not been long enough to show clinically relevant benefits. ALA is an important endogenous enzyme co-factor, also known as thioctic acid, that has shown some beneficial effects on diabetic neuropathy in short term trials. The authors of this study tested ALA in patients who had diabetic neuropathy with a follow-up period of 4 years and using an established measure of effect. Participants were patients with mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN) who were randomised to treatment with ALA 600mg daily or placebo for four years. The primary outcome was a composite of the Neuropathy Impairment Score (NIS)–Lower Limbs (NIS-LL) and seven neurophysiologic tests.

There were 879 patients screened, of whom 460 were eligible and randomised (ALA n=233, placebo n=227); two patients in each group received no study drug, and one in each group did not have primary outcome data available, so there were 454 in the final analysis. Over the study period, the score decreased compared to baseline in the ALA group, and increased in the placebo group, however the difference was not statistically significant (ALA-placebo difference in least-square means, 0.78; 95% CI 20.16 to 1.73; P = 0.105). Secondary outcomes also generally favoured ALA.

The authors conclude that their study did not show benefits for the primary outcome, although secondary outcomes favoured ALA. They comment that progression in the placebo group was less than expected, reducing the likelihood of a positive outcome with the intervention, and note that this effect has been observed in other controlled trials of interventions for peripheral neuropathy. Finally, they note the improvements in secondary outcomes, and suggest factors that will need to be considered in future trials of interventions in this condition.