Effects of acetyl‐L‐carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double‐blind, controlled trial

Abstract

Aims/IntroductionTo assess the efficacy and safety of acetyl‐L‐carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC).Materials and methodsThis was a multicenter, randomized, parallel‐group, double‐blind, double‐dummy, positive‐controlled, non‐inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up.ResultsA total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events.Conclusions ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24‐week period with good tolerance.

Effect of acetyl-l-carnitine in the treatment of diabetic peripheral neuropathy: A systematic review and meta-analysis

“…All the three RCTs [23][24][25], in fact, reported a similar frequency of side effects among people treated with ALC and controls, whilst the only descriptive study [26] reporting adverse events showed that only 2 patients were affected by an adverse effect and they did not discontinue the treatment with this supplement.…”

“…After excluding 218 articles based on title/abstract review (predominantly because they did not include participants with diabetic neuropathy), 12 articles were retrieved for full text review. Finally, six articles [22][23][24][25][26][27] were included in the qualitative synthesis and five [23][24][25][26][27] were included in the quantitative analysis. Of the included articles, three were RCTs [23][24][25] (Figure 1).…”

“…Table 1 shows the meta-analysis of EMG parameters between patients treated with ALC vs. controls in two studies. [23,24] Compared to controls, the treatment with ALC improved the nerve conduction velocity a both sensory (SMD=0.60; 95%CI: 0.35-0.86, p<0.0001; I 2 =94%) and motor (SMD=0.67; 95%CI: 0.43-0.91, p<0.0001; I 2 =0%) ulnar nerve. We observed a similar improvement for both sensory and motor component for ulnar nerve, taking response amplitude as outcome.…”

“…Figure 2 shows the effect of ALC on pain in people with diabetic neuropathy. Two studies [23,25] reported the pain perception using a Visual Analogue Scale, whilst another RCT [24] Although the data were heterogeneous, a meta-regression analysis was not possible due to the limited number of the studies available, whilst the evidence of the publication bias was low (Egger bias test=0.78; p=0.48).…”

“…The three RCTs [23][24][25] included in our meta-analysis included a total of 658 diabetic participants with neuropathy. Across the 3 RCTs, 340 were treated with ALC (mean age=57.8 years), whilst the 318 controls (mean age=57.8 years) were treated with placebo (n=203) or methylcobalamine (n=115), as reported in the Supplementary Table 1.…”