Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia.
Lancet. 2012 Jun 16;379(9833):2262-9. doi: 10.1016/S0140-6736(12)60439-5. Epub 2012 Jun 9.
In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative. We aimed to compare the efficacy, tolerability, and safety of insulin glargine and sitagliptin, a DPP-4 inhibitor, in patients whose disease was uncontrolled with metformin.
In this comparative, parallel, randomised, open-label trial, metformin-treated people aged 35-70 years with glycated haemoglobin A(1c) (HbA(1c)) of 7-11%, diagnosis of type 2 diabetes for at least 6 months, and body-mass index of 25-45 kg/m(2) were recruited from 17 countries. Participants were randomly assigned (1:1) to 24-week treatment with insulin glargine (titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0-5·5 mmol/L) or sitagliptin (oral dose of 100 mg daily). Randomisation (via a central interactive voice response system) was by random sequence generation and was stratified by centre. Patients and investigators were not masked to treatment assignment. The primary outcome was change in HbA(1c) from baseline to study end. Efficacy analysis included all randomly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable. This trial is registered at ClinicalTrials.gov, NCT00751114.
732 people were screened and 515 were randomly assigned to insulin glargine (n=250) or sitagliptin (n=265). At study end, adjusted mean reduction in HbA(1c) was greater for patients on insulin glargine (n=227; -1·72%, SE 0·06) than for those on sitagliptin (n=253; -1·13%, SE 0·06) with a mean difference of -0·59% (95% CI -0·77 to -0·42, p<0·0001). The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin (4·21 [SE 0·54] vs 0·50 [SE 0·09] events per patient-year; p<0·0001). Severe hypoglycaemia occurred in only three (1%) patients on insulin glargine and one (<1%) on sitagliptin. 15 (6%) of patients on insulin glargine versus eight (3%) on sitagliptin had at least one serious treatment-emergent adverse event.
Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin. Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease.
Sanofi.
在 2 型糖尿病患者中，在二甲双胍治疗后，二肽基肽酶-4（DPP-4）抑制剂是二线治疗选择之一，基础胰岛素是另一种选择。我们旨在比较在二甲双胍控制不佳的患者中，胰岛素甘精和西他列汀（一种 DPP-4 抑制剂）的疗效、耐受性和安全性。
在这项比较性、平行、随机、开放标签试验中，我们招募了来自 17 个国家的年龄在 35-70 岁、糖化血红蛋白 A1c（HbA1c）为 7-11%、诊断为 2 型糖尿病至少 6 个月、体重指数为 25-45 kg/m2的接受二甲双胍治疗的患者。参与者被随机分配（1:1）接受 24 周的胰岛素甘精（起始皮下剂量为 0.2 单位/公斤体重，将空腹血浆葡萄糖控制在 4.0-5.5 mmol/L）或西他列汀（每日口服 100 mg）治疗。随机化（通过中央交互式语音响应系统）采用随机序列生成，并按中心分层。患者和研究者对治疗分配不知情。主要结局是从基线到研究结束时 HbA1c 的变化。疗效分析包括至少接受过一次研究药物治疗且至少有一次主要或次要疗效变量的治疗后评估的所有随机分配参与者。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00751114。
对 732 名患者进行了筛选，515 名患者被随机分配至胰岛素甘精组（n=250）或西他列汀组（n=265）。研究结束时，接受胰岛素甘精治疗的患者（n=227）的 HbA1c 平均降低幅度大于接受西他列汀治疗的患者（n=253）（-1.72%，SE 0.06），差值为-0.59%（95%CI -0.77 至-0.42，p<0.0001）。接受胰岛素甘精治疗的患者发生所有有症状低血糖事件的估计率高于接受西他列汀治疗的患者（4.21 [SE 0.54] 与 0.50 [SE 0.09] 事件/患者年；p<0.0001）。只有 3 名（1%）接受胰岛素甘精治疗的患者和 1 名（<1%）接受西他列汀治疗的患者发生严重低血糖。15 名（6%）接受胰岛素甘精治疗的患者和 8 名（3%）接受西他列汀治疗的患者至少发生了一次严重的治疗相关不良事件。
我们的结果支持在二甲双胍控制不佳的 2 型糖尿病患者中添加基础胰岛素的选择。从疾病早期就实现最佳血糖控制，可能会带来长期获益。
赛诺菲。
