Abstract
This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was −0.05 (−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments. GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.
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Key Points
Diabetic sensorimotor distal symmetric polyneuropathy, or diabetic peripheral neuropathy (DPN), is the most common neuropathy associated with diabetes as well as the most common complication in diabetes patients. the primary aim of the present study was to investigate the noninferiority of the efficacy of GLA (Evoprim Dalim Biotech, Seoul, Korea) relative to ALA (Lipo-A HR; Dalim Biotech) as an active comparator. GLA was orally administered for 12 weeks as a treatment for the neuropathic symptoms of T2DM patients with painful DPN.Background The present study demonstrated that T2DM patients with DPN who were treated with GLA over 12 weeks showed improvements in pain severity as measured by the VAS, and that GLA was noninferior to ALA. Additionally, the mean TSS score of the GLA group improved after 12 weeks of treatment, but none of the individual symptoms, except stabbing pain, exhibited a significant change compared to baseline. Although none of the TSS measures in the GLA group met the noninferiority criteria compared to ALA, the noninferiority of symptomatic improvements in DPN due to GLA compared to ALA was supported by the secondary outcomes for efficacy. The scores on the MNSI, mBPI-DPN, and EQ 5D after 12 weeks of treatment did not differ significantly between the GLA and ALA groups. However, there were no changes in the CPT measures (except at 2,000 Hz for GLA) or mean EQ 5D scores in either group. The overall treatment demonstrated a tolerable safety profile. A total of 55 mild adverse events were observed in 37 patients (22 events in 13 GLA subjects and 33 events in 24 ALA subjects), but all were transient and self-limited.
In conclusion, the present trial demonstrated that the magnitude of efficacy of GLA treatment on pain severity (as measured by the VAS) over 12 weeks was comparable to that of ALA. Additionally, both treatments were well-tolerated and, therefore, GLA appears to be a reasonable treatment option for Korean patients with painful DPN. The present findings should be further validated by larger well-designed and high quality randomized controlled trials.