A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia

Itori Saito, Kyoichi Azuma, Taro Kakikawa, Nobuyuki Oshima, Mary E Hanson, Andrew M Tershakovec, Itori Saito, Kyoichi Azuma, Taro Kakikawa, Nobuyuki Oshima, Mary E Hanson, Andrew M Tershakovec

Abstract

Background: Recent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial. Adults with type 2 diabetes and hypercholesterolemia whose LDL-C measured <140 mg/dl (subjects receiving lipid-lowering drugs) or <160 mg/dl (subjects not receiving lipid-lowering drugs) at the start of the screening phase, were randomized after a 5-week wash-out period to ezetimibe 10 mg or placebo (1:1) for 24 weeks. Changes in HbA1c, glycoalbumin and fasting plasma glucose from baseline to week 24 were evaluated. The non-inferiority margin was set at 0.5% for HbA1c.

Results: Overall, 152 subjects were randomized (75 to ezetimibe and 77 to placebo). From baseline to 24 weeks, HbA1c significantly increased in both the ezetimibe and placebo groups (between-treatment difference 0.08 [95% CI: -0.07 to 0.23]). Ezetimibe was statistically non-inferior to placebo. At 24 weeks, the mean change from baseline in glycoalbumin levels (between-treatment differences 0.00 [95% CI: -0.47, 0.47]) and fasting plasma glucose (between-treatment differences -4.8 [95% CI: -12.1, 2.1]) were similar in both treatment groups.

Conclusions: These results suggest that ezetimibe 10 mg does not result in dysregulation of glucose metabolism in Japanese patients with type 2 diabetes and hypercholesterolemia over 24 weeks of treatment.

Trial registration: ClinicalTrials.gov identifier NCT01611883 .

Figures

Figure 1
Figure 1
Patient flow through the study.
Figure 2
Figure 2
Change from baseline in HbA1c (%) over 24 weeks of treatment with ezetimibe 10 mg or placebo (PPS).
Figure 3
Figure 3
Change from baseline in A) glycoalbumin (%) and B) fasting plasma glucose (mg/dL) over 24 weeks of treatment with ezetimibe 10 mg or placebo (PPS).
Figure 4
Figure 4
Percent change from baseline to 24 weeks in lipid parameters (FAS). No patient had triglyceride level >400 mg/dL after allocation.

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