Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
Diabet Med. 2011 Apr;28(4):464-9. doi: 10.1111/j.1464-5491.2010.03181.x.
PF-734200 is a potent and selective oral dipeptidyl peptidase-4 (DPP-4) inhibitor. This study assessed the efficacy and safety of PF-734200 at dose rates of 20 and 30 mg/day in subjects with Type 2 diabetes mellitus inadequately controlled on metformin monotherapy.
This was a placebo-controlled, double-blind, randomized, multicentre, 12 week study. Subjects with Type 2 diabetes mellitus were eligible if screening glycosylated haemoglobin (HbA(1c) ) was 7-11% (53.0-96.7 mmol/mol) and they had been receiving metformin monotherapy for ≥2 months. Subjects receiving metformin and an insulin secretagogue or metformin and thiazolidinedione needed to have a screening HbA(1c) of 6.5-9.5% (47.5-80.3 mmol/mol), measured prior to discontinuing the insulin secretagogue or thiazolidinedione. The primary end-point of the study was a change from baseline to week 12 in HbA(1c) levels.
Baseline characteristics for 289 subjects randomized to PF-734200 or placebo groups were similar (mean age 56.5 years, mean body mass index 32.2 kg/m(2) and mean HbA(1c) 8.2%, 66.1 mmol/mol). In the predefined per protocol data set, least-squares mean HbA(1c) at week 12 was reduced by 0.79 (8.6 mmol/mol 95% confidence interval -1.10 to -0.49, -12.0 to -5.4 mmol/mol) and 0.92% (10.1 mmol/mol; -1.23 to -0.61, -13.4 to -6.7 mmol/mol) in the 20 and 30 mg groups, respectively, compared with placebo. Differences from placebo were statistically significant (P<0.0001), but the differences between the 20 and 30 mg groups were not. The intent-to-treat analysis yielded similar findings.
The HbA(1c) was significantly and meaningfully reduced by both doses of PF-734200, but 20 mg appears to be the more appropriate therapeutic dose for Type 2 diabetes mellitus, contingent upon confirmation by long-term controlled studies.
PF-734200 是一种强效和选择性的口服二肽基肽酶-4（DPP-4）抑制剂。这项研究评估了 PF-734200 在 20 和 30 mg/天剂量下治疗二甲双胍单药治疗控制不佳的 2 型糖尿病患者的疗效和安全性。
这是一项安慰剂对照、双盲、随机、多中心、12 周研究。符合条件的 2 型糖尿病患者的筛选糖化血红蛋白（HbA（1c））为 7-11%（53.0-96.7 mmol/mol），且已接受二甲双胍单药治疗≥2 个月。接受二甲双胍和胰岛素促分泌剂或二甲双胍和噻唑烷二酮的患者需要在停用胰岛素促分泌剂或噻唑烷二酮之前进行 HbA（1c）的筛选，其值为 6.5-9.5%（47.5-80.3 mmol/mol）。该研究的主要终点是从基线到第 12 周 HbA（1c）水平的变化。
289 名随机分配至 PF-734200 或安慰剂组的患者的基线特征相似（平均年龄 56.5 岁，平均体重指数 32.2 kg/m²，平均 HbA（1c）8.2%，66.1 mmol/mol）。在预先设定的符合方案数据集，20 和 30 mg 组治疗 12 周后 HbA（1c）的最小二乘均值分别降低了 0.79（8.6 mmol/mol，95%置信区间-1.10 至-0.49，-12.0 至-5.4 mmol/mol）和 0.92%（10.1 mmol/mol，-1.23 至-0.61，-13.4 至-6.7 mmol/mol），与安慰剂相比。与安慰剂相比，差异具有统计学意义（P<0.0001），但 20 和 30 mg 组之间的差异无统计学意义。意向治疗分析得出了类似的结果。
PF-734200 的两种剂量均显著且有意义地降低了 HbA（1c），但 20 mg 似乎是 2 型糖尿病的更合适治疗剂量，尚需长期对照研究证实。
