Inzucchi S E, Nauck M A, Hehnke U, Woerle H-J, von Eynatten M, Henry R R
Yale-New Haven Hospital, Yale University School of Medicine, New Haven, CT, USA.
Division of Diabetology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
Diabetes Obes Metab. 2015 Sep;17(9):868-77. doi: 10.1111/dom.12490. Epub 2015 Jun 27.
To assess the efficacy, hypoglycaemia risk and other safety markers of linagliptin as an additional therapy in older patients (aged ≥70 years) inadequately controlled with basal insulin.
A prespecified safety analysis from the linagliptin trials programme was carried out to explore the hypoglycaemia risk when linagliptin was added to background basal insulin therapy in elderly patients (≥70 years). To do this, two eligible, randomized, placebo-controlled, clinical trials (NCT00954447 and NCT01084005) of 24 and ≥52 weeks, respectively, were analysed.
A total of 247 elderly individuals [mean ± standard deviation (s.d.) age 74 ± 4 years, glycated haemoglobin (HbA1c) 8.2 ± 0.8%] on basal insulin (mean ± s.d. baseline dose 36 ± 25 IU/day) were identified. Alongside placebo-adjusted change in HbA1c with linagliptin of -0.77% [95% confidence interval (CI) -0.95 to 0.59; p < 0.0001] after 24 weeks, the hazard ratios (HRs) of both overall and confirmed hypoglycaemia [blood glucose ≤3.9 mmol/l (70 mg/dl)], were significantly lower with linagliptin than with placebo: HR 0.61 (95% CI 0.39-0.97) versus 0.59 (95% CI 0.37-0.94), respectively (both p < 0.05). Moreover, significantly less confirmed hypoglycaemia was present in linagliptin-treated patients with renal impairment [HR 0.45 (95% CI 0.27-0.76)], moderate hyperglycaemia [HbA1c 7.5 to <9.0%; HR 0.51 (95% CI 0.27-0.99)], lower fasting plasma glucose levels [<152 mg/dl; HR 0.49 (95% CI 0.28-0.86)] and those treated with higher insulin doses [insulin ≥35.6 IU/day; HR 0.46 (95% CI 0.23-0.91); p < 0.05 for all]. Severe hypoglycaemia was rare and the incidence was lower with linagliptin (0.8%) versus placebo (2.5%): HR 0.21 (95% CI 0.02-2.30).
Despite improvements in hyperglycaemia and no relevant on-trial insulin dose reductions, adding linagliptin to basal insulin appears to decrease hypoglycaemia risk. The biological basis of this phenomenon warrants further research but may involve counter-regulatory effects of incretin hormones.
评估利格列汀作为基础胰岛素治疗控制不佳的老年患者（年龄≥70岁）的附加治疗的疗效、低血糖风险及其他安全性指标。
对利格列汀试验项目进行一项预先设定的安全性分析，以探讨在老年患者（≥70岁）基础胰岛素治疗背景上加用利格列汀时的低血糖风险。为此，分别分析了两项符合条件的、随机、安慰剂对照的临床试验（NCT00954447和NCT01084005），试验时长分别为24周和≥52周。
共纳入247例接受基础胰岛素治疗的老年个体[平均±标准差（s.d.）年龄74±4岁，糖化血红蛋白（HbA1c）8.2±0.8%]（基础胰岛素平均±标准差基线剂量36±25IU/天）。24周后，与安慰剂相比，利格列汀使HbA1c安慰剂校正变化为-0.77%[95%置信区间（CI）-0.95至0.59；p<0.0001]，总体低血糖和确诊低血糖[血糖≤3.9mmol/L（70mg/dl）]的风险比（HRs）均显著低于安慰剂：分别为HR 0.61（95%CI 0.39-0.97）和0.59（95%CI 0.37-0.94）（均p<0.05）。此外，利格列汀治疗的肾功能损害患者[HR 0.45（95%CI 0.27-0.76）]、中度高血糖患者[HbA1c 7.5%至<9.0%；HR 0.51（95%CI 0.27-0.99）]、空腹血糖水平较低患者[<152mg/dl；HR 0.49（95%CI 0.28-0.86）]及接受较高胰岛素剂量治疗患者[胰岛素≥35.6IU/天；HR 0.46（95%CI 0.23-0.91）]的确诊低血糖均显著较少（所有p<0.05）。严重低血糖罕见，利格列汀组发生率低于安慰剂组（0.
