Abstract

Background: Aldose reductase inhibitor (ARI) partially ameliorates cardiac vagal neuropathy (CVN) in patients with diabetes mellitus. Incretin-based therapy (IBT) has neuroprotective properties for neuropathy in mice and rat.

Materials and Methods: Effects of epalrestat as ARI, sitaglipitin as IBT, or combined ARI and IBT on CVN were examined in 42 patients with CVN and type 2 diabetes mellitus. Subjects were divided into 3 groups; group A (n =12) was treated with add-on oral epalrestat; group B (n =18) was treated with addon oral sitaglipitin; and group C (n = 12) with CVN despite treatment with epalrestat (n=6) for 1 year in group A , sitagliptin (n=5) for 1 year in group B and subcutaneously injected exenatide (n = 1) as IBT for 1 year was treated with add-on combined epalrestat and sitaglipitin, although there were no placebo in all patients with CVN. CVN was defined as maximal coefficient of variance in electrocardiographic beatto- beat interval (max CV. R-R) of three measurements during deep breathing at rest on ≤2.00%. Since disease duration was ≥20 years in each group, patient had various chronic complications and various treatments.

Results: Mean duration of treatment was 1 year. Max CV.R-R after treatment was significantly (P<0.001) increased after treatment in each group. Nevertheless, 8 (67%) and 5 patients (28%) still had CVN after treatment in groups A and B, respectively, whereas no patients had CVN after treatment in group C. There was significant difference (P <0.002) in magnitude increase of max CV. R-R after treatment between groups using ANOVA with multiple comparison test. No significant differences were observed in other variables before and after treatment between groups.

Conclusion: Sitagliptin may be more effective than epalrestat for CVN in type 2 diabetic patients, and combined epalrestat and sitagliptin may be haven a synergistic effect.