Clinical trials of diabetic neuropathy: past, present, and future

This article reviews current knowledge of the etiology of diabetic neuropathy and the outcomes and limitations of previous trials and discusses future directions for the investigation of its prevention and treatment. Proposed mechanisms for the development of diabetic neuropathy have been widely studied. It has been shown that there is improvement of nerve function associated with some short-term clinical trials of treatments that address a number of possible etiologic pathways. Improvement of morphometry has also been demonstrated in some short-term clinical trials. However, with the exception of the Diabetes Control and Complications Trial (DCCT), long-term trials with adequate statistical power to evaluate clinical outcome endpoints have not been conducted. The changes in nerve function are similar in most of the clinical trials. For instance, in four clinical trials directed at separate mechanisms (improved glucose control, high myo-inositol diet, therapy with an aldose reductase inhibitor, and therapy with supplementary gamma-linolenic acid), a similar improvement in peroneal motor velocity of 1-2 m/s is observed. This implies that each of the proposed mechanisms contributes equally to the development of neuropathy or that there is some redundancy to their mechanisms. In addition to an etiologic approach, nonspecific neural stimulants, such as gangliosides and nerve growth factors, have also been investigated for the treatment of diabetic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)