Aims: To determine the efficacy and safety of 600 mg of a-lipoic acid given i.v. over 3 weeks in diabetic patients with symptomatic polyneuropathy.
Methods: We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of -lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using a-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 (a-lipoic acid: n=716; placebo: n=542) met these eligibility criteria and were included in a metaanalysis 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 a-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (³50% 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 a-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 a-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 a-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 a-lipoic acid as 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 a-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 a-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both neuropathic symptoms and deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy.