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


BACKGROUND
ClinicalTrials.gov identifier NCT01611883 .
MSD KK, Japan development, Clinical research, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, 102-8667, Tokyo, Japan. itori.saito@merck.com.
Itori
I
Saito
MSD KK, Japan development, Clinical research, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, 102-8667, Tokyo, Japan. kyoichi_azuma@merck.com.
Kyoichi
K
Azuma
MSD KK, Japan development, Clinical research, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, 102-8667, Tokyo, Japan. taro.kakikawa@merck.com.
Taro
T
Kakikawa
MSD KK, Japan development, Clinical research, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, 102-8667, Tokyo, Japan. nobuyuki.oshima@merck.com.
Nobuyuki
N
Oshima
Merck & Co., Inc, Kenilworth, NJ, USA. mary.hanson@merck.com.
Mary E
ME
Hanson
Merck & Co., Inc, Kenilworth, NJ, USA. andrew.tershakovec@merck.com.
Andrew M
AM
Tershakovec
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D000093423:Glycated Serum Albumin
D000924:Anticholesteremic Agents; D001786:Blood Glucose; D000069438:Ezetimibe; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D014280:Triglycerides; D000093423:Glycated Serum Albumin; C517652:hemoglobin A1c protein, human