Effects of ezetimibe on glucose metabolism in patients with type 2 diabetes: A 12-week, open-label, uncontrolled, pilot study

Abstract

Background: A potential effect of ezetimibe, a novel cholesterol-absorption inhibitor, on insulin resistance has been reported in an animal model. Objective: The aim of this study was to evaluate the effects of ezetimibe on glucose metabolism in patients with type 2 diabetes mellitus (T2DM). Methods: Between March and June 2008, outpatients with T2DM who were being treated at Yokohama Sakae Kyosai Hospital, Yokohama, Japan, were enrolled in this pilot study if they had not achieved the target lipid levels recommended by the Japan Atherosclerosis Society Guidelines despite diet and exercise or a statin therapy for ≥3 months. At baseline and at 4 and 12 weeks after open-label treatment with ezetimibe 10 mg/d, the levels of lipid parameters, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA 1c), and high-sensitivity C-reactive protein were measured. Adverse effects (AEs) were assessed at each study visit by patient interviews and laboratory testing. Results: A total of 21 consecutive patients (10 men, 11 women; mean [SD] age, 72 [9] years; weight, 63.4 [10.5] kg; body mass index, 25.5 [3.2] kg/m 2) were enrolled in this study. The mean (SD) level of LDL-C decreased significantly from 146 (31) to 114 (27) mg/dL (−21%; P < 0.001) after 12 weeks of treatment with ezetimibe. The mean level of remnant-like particle cholesterol also decreased significantly from 6.5 (3.8) to 4.8 (2.2) mg/dL (−15%; P = 0.03). Treatment with ezetimibe was associated with a reduction in FPG level from 127 (31) to 119 (30) mg/dL ( P = 0.02), and HbAlc from 6.3% (0.6%) to 6.1% (0.7%) ( P = 0.003). No AEs were observed or reported during the study period. Conclusion: In this small, open-label, uncontrolled, pilot study, ezetimibe was associated with a significant decrease in lipid parameters and improvement in glucose metabolism in these patients with T2DM.