Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
OBJECTIVE
To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN).


METHODS
We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis.


RESULTS
LPO levels were reduced in both statin arms after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores.


CONCLUSIONS
EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.
Instituto de Investigación Clínica de Occidente, 45030 Guadalajara, JAL, Mexico.
Geannyne
G
Villegas-Rivera
Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
Luis Miguel
LM
Román-Pintos
Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
Ernesto Germán
EG
Cardona-Muñoz
Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
Oscar
O
Arias-Carvajal
Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
Adolfo Daniel
AD
Rodríguez-Carrizalez
Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
Rogelio
R
Troyo-Sanromán
Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, 44100 Guadalajara, JAL, Mexico.
Fermín Paul
FP
Pacheco-Moisés
Sección de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, 11340 Ciudad de México, DF, Mexico ; Department of Medicine, University of California, San Diego, CA 92093, USA.
Aldo
A
Moreno-Ulloa
Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
Alejandra Guillermina
AG
Miranda-Díaz
D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D000069438:Ezetimibe / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000627:therapeutic use*; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D019821:Simvastatin; D000069438:Ezetimibe