alpha-Lipoic acid in the treatment of diabetic polyneuropathy in Germany: Current evidence from clinical trials

Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of li fe. Near-normoglycaemia is now generally accepted as the primary approach t o prevention of diabetic neuropathy, but is not achievable in a considerabl e number of patients. In the past two decades several medical treatments th at exert their effects despite hyperglycaemia have been derived from the ex perimental pathogenetic concepts of diabetic neuropathy. Such compounds hav e been designed to improve or slow the progression of the neuropathic proce ss and are being evaluated in clinical trials, but with the exception of al pha-lipoic acid (thioctic acid) which is available in Germany, none of thes e drugs is currently available in clinical practice. Here we review the cur rent evidence from the clinical trials that assessed the therapeutic effica cy and safety of thioctic acid in diabetic polyneuropathy. Thus far, 15 cli nical trials have been completed using different study designs, durations o f treatment, doses, sample sizes, and patient populations. Within this vari ety of clinical trials, those with beneficial effects of thioctic acid on e ither neuropathic symptoms and deficits due to polyneuropathy or reduced he art rate variability resulting from cardiac autonomic neuropathy used doses of at least 600 mg per day. The following conclusions can be drawn from th e recent controlled clinical trials. 1.) Short-term treatment for 3 weeks u sing 600 mg of thioctic acid i.v, per day appears to reduce the chief sympt oms of diabetic polyneuropathy. A 3-week pilot study of 1800 mg per day giv en orally indicates that the therapeutic effect may be independent of the r oute of administration, but this needs to be confirmed in a larger sample s ize. 2.) The effect on symptoms is accompanied by an improvement of neuropa thic deficits. 3.) Oral treatment for 4-7 months tends to reduce neuropathi c deficits and improves cardiac autonomic neuropathy. 4.) Preliminary data over 2 years indicate possible long-term improvement in motor and sensory n erve conduction in the lower limbs. 5.). Clinical and postmarketing surveil lance studies have revealed a highly favourable safety profile of the drug. Based on these findings, a pivotal long-term multicenter trial of oral tre atment with thioctic acid (NATHAN I Study) is being conducted in North Amer ica and Europe aimed at slowing the progression of diabetic polyneuropathy using a clinically meaningful and reliable primary outcome measure that com bines clinical and neurophysiological assessment.