Abstract

Objective: To evaluate the efficacy and safety of Actovegin in patients with diabetic polyneuropathy.

Research design and methods: In this multicenter, randomized, double-blind trial, 567 patients with type 2 diabetes received 20 IV infusions of Actovegin (2000 mg/day) (n=281) or placebo (n=286) once daily followed by three tablets of Actovegin (1800 mg/day) or placebo three times daily for 140 days. Total Symptom Score (TSS) of the lower limbs and vibration perception threshold (VPT) were used as co-primary outcome measures, computed as the area under the curve (AUC) from repeated scores and divided by duration of exposure. Secondary endpoints included individual TSS symptoms, Neuropathy Impairment Score of the Lower Limbs (NIS-LL), and quality of life (SF-36).

Results: TSS was significantly improved during Actovegin treatment compared with placebo as assessed by AUC (-0.56 points, 95% CI: -0.85, -0.27;p=0.0003) and from baseline to 160 days (-0.86 points, 95% CI: -1.22, -0.50;p<0.0001). VPT (5 sites per foot) decreased by 3% more with Actovegin than placebo as assessed by AUC (95% CI: 0%, 6%;p=0.084) and by 5% more after 160 days (95% CI: 1%, 9%; p=0.017). NIS-LL sensory function as assessed by AUC was significantly improved with Actovegin versus placebo (-0.25, 95% CI: -0.46, -0.04;p=0.021), as was the SF-36 mental health domain. There were no differences in the incidence of adverse events between the groups.

Conclusions: Sequential IV and oral Actovegin treatment over 160 days improved neuropathic symptoms, VPT, sensory function, and quality of life in type 2 diabetes patients with diabetic polyneuropathy.