Predictors of response to treatment with actovegin for 6 months in patients with type 2 diabetes and symptomatic polyneuropathy

J Diabetes Complications. 2017 Jul;31(7):1181-1187. doi: 10.1016/j.jdiacomp.2017.03.012. Epub 2017 Mar 30.

Abstract

Aims: To evaluate two definitions of response and the predictive value of baseline covariates for response to actovegin treatment in type 2 diabetic patients with symptomatic diabetic sensorimotor polyneuropathy (DSPN).

Methods: Response to 6-months treatment with actovegin or placebo was defined as a clinically meaningful decline from baseline to 6months in (1) both Neuropathy Impairment Score of Lower Limbs (NIS-LL) ≥2 points and Total Symptom Score (TSS) >50% and (2) NIS-LL ≥2 points only. Nineteen baseline covariates were evaluated using separate logistic regression models and either both NIS-LL and TSS or NIS-LL response definitions.

Results: Intention-to-treat analysis included 567 patients. Actovegin treatment compared to placebo was associated with better odds of response (OR [95% CI] of 1.73 [1.21-2.48] for definition 1 and 1.94 [1.33-2.84] for definition 2). Significant interaction with actovegin treatment was noted only for baseline use of angiotensin receptor blockers (ARBs)/angiotensinogen converting enzyme inhibitors (ACEIs), resulting in a reduced treatment response (P=0.03).

Conclusions: Actovegin treatment was associated with a clinically meaningful response in neuropathic symptoms and/or impairments in patients with symptomatic DSPN. Since only one predictor of response to actovegin treatment was identified, this drug seems an appropriate therapy for the majority of patients with DSPN.

Keywords: Actovegin; Diabetic polyneuropathy; Neuropathic impairments; Neuropathic symptoms; Predictors of treatment.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / therapeutic use*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Neuropathies / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Interactions
  • Drug Resistance
  • Female
  • Heme / administration & dosage
  • Heme / analogs & derivatives*
  • Heme / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Intention to Treat Analysis
  • Male
  • Models, Neurological*
  • Pain / complications
  • Pain / drug therapy*
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / drug therapy*
  • Polyneuropathies / complications
  • Polyneuropathies / drug therapy*
  • Severity of Illness Index
  • Tablets

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Central Nervous System Stimulants
  • Tablets
  • Heme
  • Actovegin

Supplementary concepts

  • Neuropathy, Painful