Department of Endocrinology and Metabolism, Catholic University of Korea, Kangnamgu Seoul, Republic of Korea.
Diabetes Obes Metab. 2012 Aug;14(8):745-52. doi: 10.1111/j.1463-1326.2012.01594.x. Epub 2012 Apr 17.
To assess the 54-week efficacy of initial combination therapy with sitagliptin and pioglitazone, compared with pioglitazone monotherapy, and to assess safety in these groups during the 30 weeks after the dosage of pioglitazone was increased from 30 to 45 mg/day, in drug-naÏve patients with type 2 diabetes mellitus and inadequate glycaemic control [haemoglobin A1c (HbA1c) 8-12%].
Following a 24-week, randomized, double-blind, parallel-group study (Sitagliptin Protocol 064, Clinicaltrials.gov: NCT00397631; Yoon KH, Shockey GR, Teng R et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycaemic control and measures of beta-cell function in patients with type 2 diabetes. Int J Clin Pract 2011; 65: 154-164) in which patients were treated with the combination of sitagliptin 100 mg/day and pioglitazone 30 mg/day or monotherapy with pioglitazone 30 mg/day, patients entered a 30-week extension study. In the extension study, the pioglitazone dose was increased from 30 to 45 mg/day in both groups. Depending upon treatment allocation, patients took one tablet of sitagliptin 100 mg or matching placebo daily. Pioglitazone was administered in an open-label fashion as a single 45-mg tablet taken once daily. Patients not meeting specific glycaemic goals in the extension study were rescued with metformin therapy. Efficacy and safety results for the extension study excluded data after initiation of rescue therapy.
Of the 520 patients initially randomized, 446 completed the base study and, of these, 317 entered the extension. In this extension study cohort, the mean reductions from baseline in HbA1c and fasting plasma glucose (FPG) at the end of the base study (week 24) were -2.5% and -62.1 mg/dl with the combination of sitagliptin 100 mg and pioglitazone 30 mg versus -1.9% and -48.7 mg/dl with pioglitazone monotherapy. At the end of the extension study (week 54), the mean reduction in haemoglobin A1c (HbA1c) was -2.4% with the combination of sitagliptin 100 mg and pioglitazone 45 mg versus -1.9% with pioglitazone monotherapy [between-group difference (95% CI) = -0.5% (-0.8, -0.3)] and the mean reduction in FPG was -61.3 mg/dl versus -52.8 mg/dl, respectively [between-group difference (95% CI) = -8.5 mg/dl (-16.3, -0.7)]. Safety and tolerability of initial treatment with the combination of sitagliptin and pioglitazone and pioglitazone monotherapy were similar. As expected, increases in body weight from baseline were observed in both treatment groups at week 54: 4.8 and 4.1 kg in the combination and monotherapy groups, respectively [between-group difference (95% CI) = 0.7 kg (-0.7, 2.1)].
In this study, initial combination therapy with sitagliptin 100 mg and pioglitazone 30 mg increased to 45 mg after 24 weeks led to a substantial and durable incremental improvement in glycaemic control compared with initial treatment with pioglitazone monotherapy during a 54-week treatment period. Both initial combination therapy with sitagliptin and pioglitazone and pioglitazone monotherapy were generally well tolerated (Clinicaltrials.gov: NCT01028391).
评估在二甲双胍治疗 2 型糖尿病的初始阶段，加用二甲双胍与安慰剂相比是否可以带来更多的临床获益。
本研究为一项随机、双盲、安慰剂对照的多中心研究，纳入了 179 例新诊断的 2 型糖尿病患者，随机分为两组，分别接受二甲双胍（1700mg/d）联合安慰剂或二甲双胍（1700mg/d）联合利拉鲁肽（3.0mg/d）治疗，主要终点为治疗 26 周时两组患者糖化血红蛋白（HbA1c）的变化。
与安慰剂组相比，二甲双胍联合利拉鲁肽组患者治疗 26 周时的 HbA1c 显著降低（-1.14% vs. -0.67%，P=0.0001），体重也显著降低（-2.61kg vs. -0.86kg，P=0.0001）。两组患者的低血糖事件发生率相似。
在新诊断的 2 型糖尿病患者中，二甲双胍联合利拉鲁肽治疗 26 周可显著降低 HbA1c 水平，同时减轻体重。
