Efficacy and Tolerability of the DPP-4 Inhibitor Alogliptin Combined with Pioglitazone, in Metformin-Treated Patients with Type 2 Diabetes
Efficacy and Tolerability of the DPP-4 Inhibitor Alogliptin Combined with Pioglitazone, in Metformin-Treated Patients with Type 2 Diabetes
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DOI：
10.1210/jc.2011-2243
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Pratley, R. E.
中科院分区：
文献类型：
--
作者：
DeFronzo, R. A.;Burant, C. F.;Pratley, R. E.
背景：2型糖尿病的最佳管理仍然是一个难以捉摸的目标。针对胰岛素分泌受损和胰岛素抵抗的核心缺陷的联合治疗显示出维持血糖控制的希望。目的：本研究的目的是评估阿格列汀联合吡格列酮治疗二甲双胍治疗的2型糖尿病患者的疗效和耐受性。设计、设置和患者：我们在2型糖尿病患者中进行了一项多中心、随机、双盲、安慰剂对照、平行组研究。研究包括26周的阿格列汀治疗（12.5或25 mg qd）单药或与吡格列酮联合给药1554例接受稳定剂量二甲双胍单药治疗的患者（15、30或45 mg qd）主要结果测量：主要终点是糖化血红蛋白（HbA（1c））从基线到wk 26的变化。次要终点包括空腹血糖和β细胞功能的变化。主要分析比较了吡格列酮治疗[所有剂量汇总，吡格列酮单药治疗（Pio单药治疗）; n = 387]阿格列汀12.5 mg+任何剂量的吡格列酮（A12.5 + P; n = 390）或阿格列汀25 mg+任何剂量的吡格列酮（A25 + P; n = 390）。当加入二甲双胍时，最小二乘均值变化Pio单药治疗组HbA（1c）较基线的（LSM Delta）为-0.9 +/- 0.05%，A12.5 + P和A25 + P组均为-1.4 +/- 0.05%（两次比较P < 0.001）。A12.5 + P和A25 + P产生的空腹血糖降低（两者的LSM Δ = -2.5 +/-0.1 mmol/L）大于Pio单独（LSM Δ = -1.6 +/-0.1 mmol/L; P < 0.001）。与Pio单独给药相比，A12.5 + P和A25 + P显著改善了β细胞功能（胰岛素原：β细胞功能的胰岛素和稳态模型评估）的测量，但对胰岛素抵抗的稳态模型评估没有影响。A12.5 +/- P、A25 + P和Pio单独给药组的LSM Delta体重分别为1.8 +/-0.2、1.9 +/- 0.2和1.5 +/- 0.2 kg。A12.5 + P、A25 + P和Pio单药组分别有1.0%、1.5%和2.1%的患者报告低血糖。结论：在二甲双胍控制不佳的2型糖尿病患者中，阿格列汀和吡格列酮可使HbA（1c）降低。A12.5 + P和A25 + P的HbA（1c）下降幅度相似。所有治疗均耐受良好。（J Clin Endocrinol Metab 97：1615-1622，2012）
Context: Optimal management of type 2 diabetes remains an elusive goal. Combination therapy addressing the core defects of impaired insulin secretion and insulin resistance shows promise in maintaining glycemic control.Objective: The aim of the study was to assess the efficacy and tolerability of alogliptin combined with pioglitazone in metformin-treated type 2 diabetic patients.Design, Setting, and Patients: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study in patients with type 2 diabetes.Interventions: The study consisted of 26-wk treatment with alogliptin (12.5 or 25 mg qd) alone or combined with pioglitazone (15, 30, or 45 mg qd) in 1554 patients on stable-dose metformin monotherapy (>= 1500 mg) with inadequate glycemic control.Main Outcome Measure: The primary endpoint was change in glycosylated hemoglobin (HbA(1c)) from baseline to wk 26. Secondary endpoints included changes in fasting plasma glucose and beta-cell function. Primary analyses compared pioglitazone therapy [all doses pooled, pioglitazone alone (Pio alone); n = 387] with alogliptin 12.5 mg plus any dose of pioglitazone (A12.5 + P; n = 390) or alogliptin 25 mg plus any dose of pioglitazone (A25 + P; n = 390).Results: When added to metformin, the least squares mean change (LSM Delta) from baseline HbA(1c) was -0.9 +/- 0.05% in the Pio-alone group and -1.4 +/- 0.05% in both the A12.5 + P and A25 + P groups (P < 0.001 for both comparisons). A12.5 + P and A25 + P produced greater reductions in fasting plasma glucose (LSM Delta = -2.5 +/- 0.1 mmol/liter for both) than Pio alone (LSM Delta = -1.6 +/- 0.1 mmol/liter; P < 0.001). A12.5 + P and A25 + P significantly improved measures of beta-cell function (proinsulin: insulin and homeostasis model assessment of beta-cell function) compared to Pio alone, but had no effect on homeostasis model assessment of insulin resistance. The LSM Delta body weight was 1.8 +/- 0.2, 1.9 +/- 0.2, and 1.5 +/- 0.2 kg in A12.5 +/- P, A25 + P, and Pio-alone groups, respectively. Hypoglycemia was reported by 1.0, 1.5, and 2.1% of patients in the A12.5 + P, A25 + P, and Pio-alone groups, respectively.Conclusions: In type 2 diabetic patients inadequately controlled by metformin, the reduction in HbA(1c) by alogliptin and pioglitazone was additive. The decreases in HbA(1c) with A12.5 + P and A25 + P were similar. All treatments were well tolerated. (J Clin Endocrinol Metab 97: 1615-1622, 2012)