Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA.
MedStar Health Research Institute, Hyattsville, MD, USA.
Lancet Diabetes Endocrinol. 2018 Apr;6(4):275-286. doi: 10.1016/S2213-8587(18)30024-X. Epub 2018 Feb 1.
Despite common mechanisms of actions, glucagon-like peptide-1 receptor agonists differ in structure, pharmacokinetic profile, and clinical effects. This head-to-head trial compared semaglutide with dulaglutide in patients with inadequately controlled type 2 diabetes.
This was an open-label, parallel-group, phase 3b trial done at 194 hospitals, clinical institutions or private practices in 16 countries. Eligible patients were aged 18 years or older and had type 2 diabetes with HbA 7·0-10·5% (53·0-91·0 mmol/mol) on metformin monotherapy. Patients were randomly assigned (1:1:1:1) by use of an interactive web-response system to once a week treatment with either semaglutide 0·5 mg, dulaglutide 0·75 mg, semaglutide 1·0 mg, or dulaglutide 1·5 mg subcutaneously. The primary endpoint was change from baseline in percentage HbA; the confirmatory secondary endpoint was change in bodyweight, both at week 40. The primary analysis population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment and before the onset of rescue medication. The safety population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment. The trial was powered for HbA non-inferiority (margin 0·4%) and bodyweight superiority. This trial is registered with ClinicalTrials.gov, number NCT02648204.
Between Jan 6, 2016, and June 22, 2016, 1201 patients were randomly assigned to treatment; of these, 301 were exposed to semaglutide 0·5 mg, 299 to dulaglutide 0·75 mg, 300 to semaglutide 1·0 mg, and 299 to dulaglutide 1·5 mg. 72 (6%) patients withdrew from the trial (22 receiving semaglutide 0·5 mg, 13 receiving dulaglutide 0·75 mg, 21 receiving semaglutide 1·0 mg, and 16 receiving dulaglutide 1·5 mg). From overall baseline mean, mean percentage HbA was reduced by 1·5 (SE 0·06) percentage points with semaglutide 0·5 mg versus 1·1 (0·05) percentage points with dulaglutide 0·75 mg (estimated treatment difference [ETD] -0·40 percentage points [95% CI -0·55 to -0·25]; p<0·0001) and by 1·8 (0·06) percentage points with semaglutide 1·0 mg versus 1·4 (0·06) percentage points with dulaglutide 1·5 mg (ETD -0·41 percentage points [-0·57 to -0·25]; p<0·0001). From overall baseline mean, mean bodyweight was reduced by 4·6 kg (SE 0·28) with semaglutide 0·5 mg compared with 2·3 kg (0·27) with dulaglutide 0·75 mg (ETD -2·26 kg [-3·02 to -1·51]; p<0·0001) and by 6·5 kg (0·28) with semaglutide 1·0 mg compared with 3·0 kg (0·27) with dulaglutide 1·5 mg (ETD -3·55 kg [-4·32 to -2·78]; p<0·0001). Gastrointestinal disorders were the most frequently reported adverse event, occurring in 129 (43%) of 301 patients receiving semaglutide 0·5 mg, 133 (44%) of 300 patients receiving semaglutide 1·0 mg, 100 (33%) of 299 patients receiving dulaglutide 0·75 mg, and in 143 (48%) of 299 patients receiving dulaglutide 1·5 mg. Gastrointestinal disorders were also the most common reason for discontinuing treatment with semaglutide and dulaglutide. There were six fatalities: one in each semaglutide group and two in each dulaglutide group.
At low and high doses, semaglutide was superior to dulaglutide in improving glycaemic control and reducing bodyweight, enabling a significantly greater number of patients with type 2 diabetes to achieve clinically meaningful glycaemic targets and weight loss, with a similar safety profile.
Novo Nordisk.
尽管作用机制相同，但胰高血糖素样肽-1 受体激动剂在结构、药代动力学特征和临床效果方面存在差异。本头对头试验比较了索马鲁肽与度拉鲁肽在血糖控制不佳的 2 型糖尿病患者中的疗效。
这是一项在 16 个国家的 194 家医院、临床机构或私人诊所进行的开放性、平行组、3b 期试验。纳入标准为年龄 18 岁及以上，接受二甲双胍单药治疗时糖化血红蛋白（HbA）为 7·0-10·5%（53·0-91·0 mmol/mol）的 2 型糖尿病患者。患者按 1:1:1:1 的比例随机分配（使用交互式网络响应系统），每周接受一次皮下注射 0.5 mg 索马鲁肽、0.75 mg 度拉鲁肽、1.0 mg 索马鲁肽或 1.5 mg 度拉鲁肽治疗。主要终点为治疗 40 周时与基线相比的 HbA 百分比变化；确认性次要终点为体重变化，均在第 40 周时进行评估。主要分析人群包括所有随机分配的患者，这些患者至少接受过一次试验产品治疗，并且在开始使用抢救药物之前。安全性人群包括所有至少接受过一次试验产品治疗的随机分配患者。该试验在 HbA 非劣效性（边际 0·4%）和体重优越性方面具有统计学效能。本试验在 ClinicalTrials.gov 注册，编号为 NCT02648204。
2016 年 1 月 6 日至 2016 年 6 月 22 日，共纳入 1201 例患者进行随机分组；其中 301 例患者接受索马鲁肽 0·5 mg 治疗，299 例患者接受度拉鲁肽 0·75 mg 治疗，300 例患者接受索马鲁肽 1·0 mg 治疗，299 例患者接受度拉鲁肽 1·5 mg 治疗。72 例（6%）患者退出试验（22 例接受索马鲁肽 0·5 mg 治疗，13 例接受度拉鲁肽 0·75 mg 治疗，21 例接受索马鲁肽 1·0 mg 治疗，16 例接受度拉鲁肽 1·5 mg 治疗）。从总体基线平均值来看，与接受度拉鲁肽 0·75 mg 治疗的患者相比，接受索马鲁肽 0·5 mg 治疗的患者的 HbA 百分比降低了 1·5（SE 0·06）个百分点，接受度拉鲁肽 1·5 mg 治疗的患者降低了 1·8（SE 0·06）个百分点（估计治疗差异[ETD]为-0·40 个百分点[-0·55 至-0·25]；p<0·0001）。与接受度拉鲁肽 1·5 mg 治疗的患者相比，接受索马鲁肽 1·0 mg 治疗的患者的体重降低了 4·6（SE 0·28）kg，接受度拉鲁肽 1·5 mg 治疗的患者降低了 2·3（SE 0·27）kg（ETD-2·26 kg [-3·02 至-1·51]；p<0·0001）。与接受度拉鲁肽 1·5 mg 治疗的患者相比，接受索马鲁肽 1·0 mg 治疗的患者的体重降低了 6·5（SE 0·28）kg，接受度拉鲁肽 1·5 mg 治疗的患者降低了 3·0（SE 0·27）kg（ETD-3·55 kg [-4·32 至-2·78]；p<0·0001）。最常报告的不良事件是胃肠道疾病，在接受索马鲁肽 0·5 mg 治疗的 301 例患者中，有 129 例（43%），接受索马鲁肽 1·0 mg 治疗的 300 例患者中，有 133 例（44%），接受度拉鲁肽 0·75 mg 治疗的 299 例患者中，有 100 例（33%），接受度拉鲁肽 1·5 mg 治疗的 299 例患者中，有 143 例（48%）。胃肠道疾病也是导致索马鲁肽和度拉鲁肽停药的最常见原因。共有 6 例死亡：索马鲁肽组各 1 例，度拉鲁肽组各 2 例。
在低剂量和高剂量时，索马鲁肽在改善血糖控制和减轻体重方面均优于度拉鲁肽，使更多的 2 型糖尿病患者能够达到有临床意义的血糖目标和减重目标，且安全性特征相似。
诺和诺德。
