Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid

A meta-analysis

D. Ziegler, H. Nowak, P. Kempler, P. Vargha, Phillip Anson Low

Research output: Contribution to journalArticle

358 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)114-121
Number of pages8
JournalDiabetic Medicine
Volume21
Issue number2
DOIs
StatePublished - Feb 2004

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Thioctic Acid
Diabetic Neuropathies
Meta-Analysis
Antioxidants
Placebos
Polyneuropathies
Therapeutics
Hypesthesia
Touch
Ankle
Germany
Reflex
Foot
Lower Extremity
Clinical Trials

Keywords

  • α-lipoic acid
  • Diabetic polyneuropathy
  • Meta-analysis
  • Neuropathy Impairment Score
  • Total Symptom Score

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid : A meta-analysis. / Ziegler, D.; Nowak, H.; Kempler, P.; Vargha, P.; Low, Phillip Anson.

In: Diabetic Medicine, Vol. 21, No. 2, 02.2004, p. 114-121.

Research output: Contribution to journalArticle

Ziegler, D. ; Nowak, H. ; Kempler, P. ; Vargha, P. ; Low, Phillip Anson. / Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid : A meta-analysis. In: Diabetic Medicine. 2004 ; Vol. 21, No. 2. pp. 114-121.
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N2 - 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.

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