Clinical Research, National Research Institute, Los Angeles, CA, USA.
Novo Nordisk, Søborg, Denmark.
Lancet Diabetes Endocrinol. 2021 Sep;9(9):563-574. doi: 10.1016/S2213-8587(21)00174-1. Epub 2021 Jul 21.
Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea.
We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (≥18 years) with inadequately controlled type 2 diabetes (HbA 8·0-10·0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2·0 mg or 1·0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162.
Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58·0 years [SD 10·0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2·0 mg (n=480 [50%]) or 1·0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2·0 mg group and 471 (98%) in the semaglutide 1·0 mg group completed the trial. Mean baseline HbA was 8·9% (SD 0·6; 73·3 mmol/mol [SD 6·9]) and BMI was 34·6 kg/m (SD 7·0). Mean change in HbA from baseline at week 40 was -2·2 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (estimated treatment difference [ETD] -0·23 percentage points [95% CI -0·36 to -0·11]; p=0·0003; trial product estimand) and -2·1 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (ETD -0·18 percentage points [-0·31 to -0·04]; p=0·0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6·9 kg with semaglutide 2·0 mg and -6·0 kg with semaglutide 1·0 mg (ETD -0·93 kg [95% CI -1·68 to -0·18]; p=0·015; trial product estimand) and -6·4 kg with semaglutide 2·0 mg and -5·6 kg with semaglutide 1·0 mg (ETD -0·77 kg [-1·55 to 0·01]; p=0·054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2·0 mg group and 148 [31%] in the 1·0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2·0 mg and 25 (5%) participants given semaglutide 1·0 mg. Three deaths were reported during the trial (one in the semaglutide 1·0 mg group and two in the semaglutide 2·0 mg group).
Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control.
Novo Nordisk.
司美格鲁肽是治疗 2 型糖尿病的有效药物；然而，接受司美格鲁肽 1.0mg 治疗的患者中，有 20-30%未达到血糖治疗目标。我们旨在研究每周一次司美格鲁肽 2.0mg 与 1.0mg 在稳定剂量二甲双胍联合或不联合磺酰脲类药物治疗下对血糖控制不佳的 2 型糖尿病患者的疗效和安全性。
我们在 10 个国家的 125 家门诊诊所进行了一项 40 周、随机、活性对照、平行组、双盲、3b 期试验（SUSTAIN FORTE）。纳入（年龄≥18 岁）接受二甲双胍联合或不联合磺酰脲类药物治疗、血糖控制不佳（HbA1c8.0-10.0%）的 2 型糖尿病患者，按 1:1 比例通过交互式网络应答系统随机分配至 2.0mg 或 1.0mg 每周一次司美格鲁肽治疗组。参与者、现场工作人员、临床研究组和研究者对随机治疗均设盲。主要结局为治疗 40 周时 HbA1c（首要结局）和体重（次要确认性结局）的变化，通过试验产品估计值（无治疗中断或无抢救药物）和治疗方案估计值（无论是否治疗中断或抢救药物）策略进行评估。这项研究在 ClinicalTrials.gov 注册，NCT03989232；EudraCT，2018-004529-96；和 WHO，U1111-1224-5162。
2019 年 6 月 19 日至 11 月 28 日，在评估的 1515 名符合条件的成年人中，961 名（平均年龄 58.0 岁[标准差 10.0]；398 [41%]名女性）入选。参与者被随机分配至每周一次司美格鲁肽 2.0mg 组（n=480 [50%]）或 1.0mg 组（n=481 [50%]）；462 名（96%）司美格鲁肽 2.0mg 组患者和 471 名（98%）司美格鲁肽 1.0mg 组患者完成了试验。平均基线 HbA1c 为 8.9%（标准差 0.6；73.3mmol/mol[标准差 6.9]）和 BMI 为 34.6kg/m（标准差 7.0）。治疗 40 周时，与司美格鲁肽 1.0mg 组相比，司美格鲁肽 2.0mg 组 HbA1c 降低了 2.2 个百分点，司美格鲁肽 1.0mg 组降低了 1.9 个百分点（估计治疗差异[ETD] -0.23 个百分点[-0.36 至-0.11]；p=0.0003；试验产品估计值），司美格鲁肽 2.0mg 组降低了 2.1 个百分点，司美格鲁肽 1.0mg 组降低了 1.9 个百分点（ETD -0.18 个百分点[-0.31 至-0.04]；p=0.0098；治疗方案估计值）。治疗 40 周时，与司美格鲁肽 1.0mg 组相比，司美格鲁肽 2.0mg 组体重减轻了 6.9kg，司美格鲁肽 1.0mg 组减轻了 6.0kg（ETD -0.93kg[-1.68 至-0.18]；p=0.015；试验产品估计值），司美格鲁肽 2.0mg 组减轻了 6.4kg，司美格鲁肽 1.0mg 组减轻了 5.6kg（ETD -0.77kg[-1.55 至 0.01]；p=0.054；治疗方案估计值）。胃肠道疾病是最常见的不良事件（司美格鲁肽 2.0mg 组 163 例[34%]，司美格鲁肽 1.0mg 组 148 例[31%]）。严重不良事件在治疗组之间相似，司美格鲁肽 2.0mg 组报告 21 例（4%），司美格鲁肽 1.0mg 组报告 25 例（5%）。试验期间报告了 3 例死亡（司美格鲁肽 1.0mg 组 1 例，司美格鲁肽 2.0mg 组 2 例）。
与 1.0mg 相比，司美格鲁肽 2.0mg 降低 HbA1c 的效果更好，体重进一步减轻，安全性相似。这种更高的剂量为需要额外血糖控制的接受司美格鲁肽治疗的 2 型糖尿病患者提供了一种治疗强化选择。
诺和诺德。
