Saito Itori, Azuma Kyoichi, Kakikawa Taro, Oshima Nobuyuki, Hanson Mary E, Tershakovec Andrew M
MSD KK, Japan development, Clinical research, Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, 102-8667, Tokyo, Japan.
Merck & Co., Inc, Kenilworth, NJ, USA.
Lipids Health Dis. 2015 May 1;14:40. doi: 10.1186/s12944-015-0036-z.
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.
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.
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.
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.
ClinicalTrials.gov identifier NCT01611883 .
近期证据表明，他汀类药物的使用会使新发糖尿病的发病率增加，并对血糖参数产生负面影响。本研究在患有2型糖尿病和高胆固醇血症的日本受试者中，考察了依折麦布与安慰剂相比，从基线至第24周时糖化血红蛋白（主要终点）、糖化白蛋白和空腹血糖（次要终点）变化的安全性。
这是一项随机、双盲、安慰剂对照、平行组、多中心试验。在筛查阶段开始时，低密度脂蛋白胆固醇（LDL-C）测量值＜140mg/dl（接受降脂药物治疗的受试者）或＜160mg/dl（未接受降脂药物治疗的受试者）的2型糖尿病和高胆固醇血症成人患者，在经过5周的洗脱期后，随机分为依折麦布（10mg）组或安慰剂组（1:1），治疗24周。评估从基线至第24周糖化血红蛋白、糖化白蛋白和空腹血糖的变化。糖化血红蛋白的非劣效性界值设定为0.5%。
总体而言，152名受试者被随机分组（75名接受依折麦布治疗，77名接受安慰剂治疗）。从基线至24周，依折麦布组和安慰剂组的糖化血红蛋白均显著升高（组间差异0.08[95%CI：-0.07至0.23]）。依折麦布在统计学上不劣于安慰剂。在24周时，两组糖化白蛋白水平从基线的平均变化（组间差异0.00[95%CI：-0.47，0.47]）和空腹血糖（组间差异-4.8[95%CI：-12.1，2.1]）相似。
这些结果表明，在24周的治疗期间，10mg依折麦布不会导致患有2型糖尿病和高胆固醇血症的日本患者糖代谢失调。
ClinicalTrials.gov标识符NCT01611883 。
