Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
Department of Metabolic Medicine, Kumamoto University, Kumamoto, Japan.
Diabetes Obes Metab. 2019 Dec;21(12):2674-2683. doi: 10.1111/dom.13856. Epub 2019 Aug 28.
To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with its individual components in Japanese people with type 2 diabetes (T2D) uncontrolled on an oral antidiabetic drug (OAD).
This 52-week, open-label, multicentre, treat-to-target trial randomized participants (n = 819) 1:1:1 to IDegLira, liraglutide 1.8 mg or degludec, as add-on to their pre-trial OAD. The maximum IDegLira dose was 50 dose steps (50 U degludec/1.8 mg liraglutide), there was no maximum dose for degludec, and both were titrated based on individual blood glucose measurements.
After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were -6.91 mmol/mol (95% confidence interval [CI] -8.18; -5.64) and -5.30 mmol/mol (95% CI -6.58; -4.03), confirming non-inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]). Mean body weight changes were 2.9 kg, 4.1 kg and -1.0 kg with IDegLira, degludec and liraglutide, respectively, showing superiority of IDegLira versus degludec (P = .0001), but a significant difference in favour of liraglutide (P < .0001). Rates of severe or blood glucose-confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001). Mean daily total insulin dose was lower with IDegLira (27.7 U) versus degludec (34.8 U; P < .0001). Overall adverse event (AE) rates were similar. In total, 34.9%, 22.9% and 41.8% of IDegLira-, degludec- and liraglutide-treated participants experienced gastrointestinal AEs.
IDegLira was superior to degludec and liraglutide in terms of HbA1c reduction and superior to degludec in terms of body weight change and rates of hypoglycaemia in Japanese people with T2D.
旨在研究在口服降糖药（OAD）控制不佳的日本 2 型糖尿病（T2D）患者中，德谷胰岛素/利拉鲁肽（IDegLira）与各单一组分相比的疗效和安全性。
这是一项为期 52 周、开放性、多中心、以目标为导向的试验，将 819 名参与者按 1:1:1 的比例随机分配至 IDegLira、利拉鲁肽 1.8mg 或德谷胰岛素，作为其预试验 OAD 的附加治疗。IDegLira 的最大剂量为 50 个剂量级（50U 德谷胰岛素/1.8mg 利拉鲁肽），德谷胰岛素没有最大剂量，两者均根据个体血糖测量结果进行滴定。
52 周后，IDegLira 组糖化血红蛋白（HbA1c）降低 26mmol/mol，而德谷胰岛素组和利拉鲁肽组降低 20mmol/mol：估计治疗差异分别为-6.91mmol/mol（95%置信区间[CI] -8.18；-5.64）和-5.30mmol/mol（95%CI -6.58；-4.03），证实 IDegLira 与德谷胰岛素相比具有非劣效性，且 IDegLira 优于利拉鲁肽（两者均为[主要终点]，P < 0.0001）。IDegLira、德谷胰岛素和利拉鲁肽组的平均体重变化分别为 2.9kg、4.1kg 和-1.0kg，IDegLira 组与德谷胰岛素组相比具有优势（P = 0.0001），但与利拉鲁肽组相比具有显著差异（P < 0.0001）。IDegLira 组严重或血糖确认的低血糖发生率低于德谷胰岛素组（发生率比 0.48 [95%CI 0.35；0.68]；P < 0.0001），但高于利拉鲁肽组（发生率比 37.58 [95%CI 19.80；71.31]；P < 0.0001）。IDegLira 组的平均每日总胰岛素剂量（27.7U）低于德谷胰岛素组（34.8U；P < 0.0001）。总体不良事件（AE）发生率相似。IDegLira、德谷胰岛素和利拉鲁肽组分别有 34.9%、22.9%和 41.8%的患者发生胃肠道 AE。
在日本 T2D 患者中，与德谷胰岛素和利拉鲁肽相比，IDegLira 在降低 HbA1c 方面更具优势，与德谷胰岛素相比，在降低体重和低血糖发生率方面更具优势。
