Treatment of symptomatic diabetic polyneuropathy with the antioxidant α‐lipoic acid: a meta‐analysis

Abstract

Aims To determine the efficacy and safety of 600 mg of α‐lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. Methods We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of α‐lipoic acid according to the following prerequisites: randomized, double‐masked, placebo‐controlled, parallel‐group trial using α‐lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n = 1258 patients (α‐lipoic acid n = 716; placebo n = 542) met these eligibility criteria and were included in a meta‐analysis based on the intention‐to‐treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with α‐lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (≥ 50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS‐LL), individual NIS‐LL components, and the rates of adverse events. Results After 3 weeks the relative difference in favour of α‐lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS‐LL. The responder rates were 52.7% in patients treated with α‐lipoic acid and 36.9% in those on placebo (P < 0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of α‐lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of α‐lipoic acid compared with placebo, while among the NIS‐LL components pin‐prick and touch‐pressure sensation as well as ankle reflexes were improved in favour of α‐lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. Conclusions The results of this meta‐analysis provide evidence that treatment with α‐lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy. Diabet. Med. 21, 114–121 (2004)