Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin
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DOI：
10.1111/j.1463-1326.2007.00744.x
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发表时间：
2007-09-01
影响因子：
5.8
通讯作者：
Stein, P.
中科院分区：
文献类型：
--
作者：
Hermansen, K.;Kipnes, M.;Stein, P.
目的：评估西格列汀（一种高选择性每日一次口服二肽基肽酶-4（DPP-4）抑制剂）治疗24周的疗效和安全性，单药治疗血糖控制不佳[糖化血红蛋白（HbA（1c））≥ 7.5%且≥ 4 mg/d]的2型糖尿病患者和229例接受格列美脲治疗的患者（>= 4 mg/天）加二甲双胍（>= 1500 mg/天）联合治疗。在双盲治疗期间超过预先规定的血药浓度阈值的患者接受开放标签补救治疗（吡格列酮），直至研究结束。主要疗效分析评价了HbA 1c自基线至第24周的变化。次要疗效终点包括空腹血糖（FPG），2小时餐后血糖和血脂measurements.Results：平均基线HbA 1c为8.34%，西格列汀和安慰剂组。24周后，与安慰剂相比，西格列汀使HbA 1c降低0.74%（p < 0.001）。在接受格列美脲+二甲双胍治疗的患者亚组中，与安慰剂相比，西格列汀使HbA 1c降低了0.89%，而在接受格列美脲单药治疗的患者亚组中降低了0.57%。与安慰剂相比，添加西格列汀使FPG降低20.1 mg/dl（p < 0.001），并使稳态模型评估-β（β细胞功能的标志物）增加12%（p < 0.05）。在接受膳食耐量试验的患者中（n = 134），与安慰剂相比，西格列汀使餐后2小时血糖（PPG）降低36.1 mg/dl（p < 0.001）。添加西格列汀通常耐受良好，尽管西格列汀组的总体（60 vs. 47%）和药物相关不良事件（AE）（15 vs. 7%）发生率高于安慰剂组。这主要是因为西格列汀组低血糖AE的发生率高于安慰剂组（分别为12%和2%）。与安慰剂组相比，西格列汀组患者的体重略有增加（+0.8 vs-0.4 kg; p < 0.001）。结论：西格列汀100 mg每日一次显著改善了格列美脲或格列美脲加二甲双胍治疗后血糖控制不佳的2型糖尿病患者的血糖控制和β细胞功能。加用西格列汀通常耐受性良好，低血糖和体重适度增加，与格列美脲治疗和观察到的血糖改善程度一致。
Aim: To assess the efficacy and safety of a 24-week treatment with sitagliptin, a highly selective once-daily oral dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >= 7.5%and = 4 mg/day) monotherapy and 229 were on glimepiride (>= 4 mg/day) plus metformin (>= 1500 mg/day) combination therapy. Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy (pioglitazone) until study end. The primary efficacy analysis evaluated the change in HbA1c from baseline to Week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), 2-h post-meal glucose and lipid measurements.Results: Mean baseline HbA1c was 8.34% in the sitagliptin and placebo groups. After 24 weeks, sitagliptin reduced HbA1c by 0.74% (p < 0.001) relative to placebo. In the subset of patients on glimepiride plus metformin, sitagliptin reduced HbA1c by 0.89% relative to placebo, compared with a reduction of 0.57% in the subset of patients on glimepiride alone. The addition of sitagliptin reduced FPG by 20.1 mg/dl (p < 0.001) and increased homeostasis model assessment-beta, a marker of beta-cell function, by 12% (p < 0.05) relative to placebo. In patients who underwent a meal tolerance test (n = 134), sitagliptin decreased 2-h post-prandial glucose (PPG) by 36.1 mg/dl (p < 0.001) relative to placebo. The addition of sitagliptin was generally well tolerated, although there was a higher incidence of overall (60 vs. 47%) and drug-related adverse experiences (AEs) (15 vs. 7%) in the sitagliptin group than in the placebo group. This was largely because of a higher incidence of hypoglycaemia AEs (12 vs. 2%, respectively) in the sitagliptin group compared with the placebo group. Body weight modestly increased with sitagliptin relative to placebo (+0.8 vs. -0.4 kg; p < 0.001).Conclusions: Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy. The addition of sitagliptin was generally well tolerated, with a modest increase in hypoglycaemia and body weight, consistent with glimepiride therapy and the observed degree of glycaemic improvement.