Factors That Impact Symptomatic Diabetic Peripheral Neuropathy in Placebo-Administered Patients From Two 1-Year Clinical Trials

Abstract

OBJECTIVE—The purpose of this study was to evaluate the change in neuropathy symptoms and disease progression in placebo-administered patients from two 1-year studies in which the impact of ruboxistaurin (RBX) in mild diabetic peripheral neuropathy (DPN) was tested. RESEARCH DESIGN AND METHODS—Data from 262 placebo-administered patients from two identical phase 3, randomized, double-blind trials were combined and analyzed. RESULTS—After 1 year, change in the neuropathy impairment score of lower limbs [NIS(LL)] (−0.63 points; P = 0.005), vibration detection threshold (VDT) (−0.42 just noticeable difference units; P = 0.003), and Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire (−3.73 points; P < 0.001) improved, whereas some electrophysiology measures and heart rate deep breathing (HRDB) (−0.78 beats; P = 0.003) worsened compared with baseline values. There was a small but significant worsening of A1C (0.28%; P < 0.001), and a greater percentage of patients were using analgesics at the end of the trials (33.6%; P = 0.003). At 1 year, the change in NTSS-6 directly correlated with changes in NIS(LL) and VDT and inversely correlated with the peroneal nerve conduction velocity. On logistic regression analyses, a ≥50% reduction in NTSS-6 score was less likely in patients who used antihypertensive or chronic symptom medication at baseline. CONCLUSIONS—In placebo-administered patients with mild symptomatic DPN, there was a progressive improvement in symptoms over 12 months, whereas nerve conduction studies and HRDB declined, and clinically significant worsening of DPN would require >1 year of observation.