Goldstein Barry J, Feinglos Mark N, Lunceford Jared K, Johnson Jeremy, Williams-Herman Debora E
Division of Endocrinology, Diabetes, and Metabolic Diseases, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Diabetes Care. 2007 Aug;30(8):1979-87. doi: 10.2337/dc07-0627. Epub 2007 May 7.
To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control on diet and exercise.
In a 24-week, randomized, double-blind, placebo-controlled, parallel-group study, 1,091 patients with type 2 diabetes and A1C 7.5-11% were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagliptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg (M1000 group), metformin 2,000 mg (M2000 group) (all as divided doses administered twice daily [b.i.d.]), sitagliptin 100 mg q.d. (S100 group), or placebo. Patients who had an A1C >11% or a fasting glucose value >280 mg/dl after the run-in period were not eligible to be randomized; these patients could participate in an open-label substudy and were treated with S100/M2000 for 24 weeks.
The mean baseline A1C was 8.8% in the randomized patients. The placebo-subtracted A1C change from baseline was -2.07% (S100/M2000), -1.57% (S100/M1000), -1.30% (M2000), -0.99% (M1000), and -0.83% (S100) (P < 0.001 for comparisons versus placebo and for coadministration versus respective monotherapies). The proportion of patients achieving an A1C <7% and <6.5% was 66 and 44%, respectively, in the S100/M2000 group (P < 0.001 vs. S100 or M2000). For the open-label cohort (n = 117; baseline A1C 11.2%) treated with S100/M2000, the within-group mean A1C change from baseline was -2.9%. The incidence of hypoglycemia was low (0.5-2.2%) across active treatment groups and not significantly different from that in the placebo group (0.6%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapy.
The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well tolerated in patients with type 2 diabetes.
评估西格列汀与二甲双胍初始联合治疗对饮食和运动血糖控制不佳的2型糖尿病患者的疗效和安全性。
在一项为期24周的随机、双盲、安慰剂对照、平行组研究中，1091例糖化血红蛋白（A1C）为7.5%-11%的2型糖尿病患者被随机分为六种每日治疗方案之一：西格列汀100毫克/二甲双胍1000毫克（S100/M1000组）、西格列汀100毫克/二甲双胍2000毫克（S100/M2000组）、二甲双胍1000毫克（M1000组）、二甲双胍2000毫克（M2000组）（均为分剂量，每日两次给药[b.i.d.]）、西格列汀100毫克每日一次（S100组）或安慰剂。导入期后A1C>11%或空腹血糖值>280毫克/分升的患者无资格随机分组；这些患者可参与一项开放标签的亚研究，并接受S100/M2000治疗24周。
随机分组患者的平均基线A1C为8.8%。与安慰剂相比以及联合用药与各自单药治疗相比，从基线开始减去安慰剂后的A1C变化分别为-2.07%（S100/M2000）、-1.57%（S100/M1000）、-1.30%（M2000）、-0.99%（M1000）和-0.83%（S100）（P<0.001）。S100/M2000组中A1C<7%和<6.5%的患者比例分别为66%和44%（与S100或M2000相比，P<0.001）。对于接受S100/M2000治疗的开放标签队列（n=117；基线A1C 11.2%），组内从基线开始的平均A1C变化为-2.9%。各活性治疗组低血糖发生率较低（0.5%-2.2%），与安慰剂组（0.6%）无显著差异。联合用药治疗的胃肠道不良事件发生率与其各自的二甲双胍单药治疗相似。
西格列汀与二甲双胍初始联合治疗可显著且额外改善血糖，2型糖尿病患者总体耐受性良好。
