Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan.
Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Diabetes Obes Metab. 2018 May;20(5):1202-1212. doi: 10.1111/dom.13218. Epub 2018 Feb 21.
To evaluate the safety and efficacy of once-weekly subcutaneous semaglutide as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional OAD added to background therapy in Japanese people with type 2 diabetes (T2D) inadequately controlled on diet/exercise or OAD monotherapy.
In this phase III, open-label trial, adults with T2D were randomized 2:2:1 to semaglutide 0.5 mg or 1.0 mg, or one additional OAD (a dipeptidyl peptidase-4 inhibitor, biguanide, sulphonylurea, glinide, α-glucosidase inhibitor or thiazolidinedione) with a different mode of action from that of background therapy. The primary endpoint was number of adverse events (AEs) after 56 weeks.
Baseline characteristics were balanced between treatment arms (601 randomized). More AEs were reported in the semaglutide 0.5 mg (86.2%) and 1.0 mg (88.0%) groups than in the additional OAD group (71.7%). These were typically mild/moderate. Gastrointestinal AEs were most frequent with semaglutide, which diminished over time. The mean glycated haemoglobin (HbA1c) concentration (baseline 8.1%) was significantly reduced with semaglutide 0.5 mg and 1.0 mg vs additional OAD (1.7% and 2.0% vs 0.7%, respectively; estimated treatment difference [ETD] vs additional OAD -1.08% and -1.37%, both P < .0001). Body weight (baseline 71.5 kg) was reduced by 1.4 kg and 3.2 kg with semaglutide 0.5 mg and 1.0 mg, vs a 0.4-kg increase with additional OAD (ETD -1.84 kg and -3.59 kg; both P < .0001). For semaglutide-treated participants, >80% achieved an HbA1c concentration <7.0% (Japanese Diabetes Society target).
Semaglutide was well tolerated, with no new safety issues identified. Semaglutide treatment significantly reduced HbA1c and body weight vs additional OAD treatment in Japanese people with T2D.
评估每周皮下注射一次司美格鲁肽作为单药治疗或与口服降糖药（OAD）联合治疗，与在饮食/运动或 OAD 单药治疗控制不佳的日本 2 型糖尿病（T2D）患者的基础治疗中添加另一种 OAD 相比的安全性和疗效。
在这项 III 期、开放标签试验中，T2D 成年患者按 2:2:1 的比例随机分配至司美格鲁肽 0.5mg 或 1.0mg 组，或与背景治疗作用机制不同的另一种 OAD（二肽基肽酶-4 抑制剂、双胍类、磺脲类、格列奈类、α-葡萄糖苷酶抑制剂或噻唑烷二酮类）组。主要终点为 56 周后的不良事件（AE）发生数。
治疗组之间的基线特征平衡（601 例随机分组）。司美格鲁肽 0.5mg（86.2%）和 1.0mg（88.0%）组报告的 AE 多于添加 OAD 组（71.7%）。这些 AE 通常为轻/中度。胃肠道 AE 最常见于司美格鲁肽，且随着时间的推移而减少。糖化血红蛋白（HbA1c）浓度（基线 8.1%）的均值显著降低，与添加 OAD 相比，司美格鲁肽 0.5mg 和 1.0mg 组分别降低 1.7%和 2.0%（分别为 0.7%；估计治疗差异[ETD]与添加 OAD 组相比分别为-1.08%和-1.37%，均<0.0001）。司美格鲁肽 0.5mg 和 1.0mg 组体重（基线 71.5kg）分别减轻 1.4kg 和 3.2kg，而添加 OAD 组体重增加 0.4kg（ETD 分别为-1.84kg 和-3.59kg；均<0.0001）。对于接受司美格鲁肽治疗的参与者，超过 80%的患者达到了 HbA1c<7.0%（日本糖尿病学会目标）。
司美格鲁肽耐受良好，未发现新的安全性问题。与添加 OAD 治疗相比，司美格鲁肽治疗可显著降低 HbA1c 和体重，改善日本 T2D 患者的血糖控制。
