Velocity Clinical Research, Los Angeles, CA, USA.
Novo Nordisk, Søborg, Denmark.
Lancet. 2023 Aug 26;402(10403):720-730. doi: 10.1016/S0140-6736(23)01163-7. Epub 2023 Jun 23.
Combining the GLP-1 receptor agonist semaglutide with the long-acting amylin analogue cagrilintide has weight-loss benefits; the impact on glycated haemoglobin (HbA) is unknown. This trial assessed the efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes.
This 32-week, multicentre, double-blind, phase 2 trial was conducted across 17 sites in the USA. Adults with type 2 diabetes and a BMI of 27 kg/m or higher on metformin with or without an SGLT2 inhibitor were randomly assigned (1:1:1) to once-weekly subcutaneous CagriSema, semaglutide, or cagrilintide (all escalated to 2·4 mg). Randomisation was done centrally using an interactive web response system and was stratified according to use of SGLT2 inhibitor treatment (yes vs no). The trial participants, investigators, and trial sponsor staff were masked to treatment assignment throughout the trial. The primary endpoint was change from baseline in HbA; secondary endpoints were bodyweight, fasting plasma glucose, continuous glucose monitoring (CGM) parameters, and safety. Efficacy analyses were performed in all participants who had undergone randomisation, and safety analyses in all participants who had undergone randomisation and received at least one dose of the trial medication. This trial is registered on ClinicalTrials.gov (NCT04982575) and is complete.
Between Aug 2 and Oct 18, 2021, 92 participants were randomly assigned to CagriSema (n=31), semaglutide (n=31), or cagrilintide (n=30). 59 (64%) participants were male; the mean age of participants was 58 years (SD 9). The mean change in HbA from baseline to week 32 (CagriSema: -2·2 percentage points [SE 0·15]; semaglutide: -1·8 percentage points [0·16]; cagrilintide: -0·9 percentage points [0·15]) was greater with CagriSema versus cagrilintide (estimated treatment difference -1·3 percentage points [95% CI -1·7 to -0·8]; p<0·0001), but not versus semaglutide (-0·4 percentage points [-0·8 to 0·0]; p=0·075). The mean change in bodyweight from baseline to week 32 (CagriSema: -15·6% [SE 1·26]; semaglutide: -5·1% [1·26]; cagrilintide: -8·1% [1·23]) was greater with CagriSema versus both semaglutide (p<0·0001) and cagrilintide (p<0·0001). The mean change in fasting plasma glucose from baseline to week 32 (CagriSema: -3·3 mmol/L [SE 0·3]; semaglutide: -2·5 mmol/L [0·4]; cagrilintide: -1·7 mmol/L [0·3]) was greater with CagriSema versus cagrilintide (p=0·0010) but not versus semaglutide (p=0·10). Time in range (3·9-10·0 mmol/L) was 45·9%, 32·6%, and 56·9% at baseline and 88·9%, 76·2%, and 71·7% at week 32 with CagriSema, semaglutide, and cagrilintide, respectively. Adverse events were reported by 21 (68%) participants in the CagriSema group, 22 (71%) in the semaglutide group, and 24 (80%) in the cagrilintide group. Mild or moderate gastrointestinal adverse events were most common; no level 2 or 3 hypoglycaemia was reported. No fatal adverse events were reported.
In people with type 2 diabetes, treatment with CagriSema resulted in clinically relevant improvements in glycaemic control (including CGM parameters). The mean change in HbA with CagriSema was greater versus cagrilintide, but not versus semaglutide. Treatment with CagriSema resulted in significantly greater weight loss versus semaglutide and cagrilintide and was well tolerated. These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.
Novo Nordisk.
将 GLP-1 受体激动剂司美格鲁肽与长效胰淀素类似物卡格列净联合使用具有减肥效果；对糖化血红蛋白（HbA）的影响尚不清楚。本试验评估了在 2 型糖尿病患者中联合使用司美格鲁肽和卡格列净（CagriSema）的疗效和安全性。
这是一项在美国 17 个地点进行的 32 周、多中心、双盲、2 期临床试验。接受二甲双胍治疗且 BMI 为 27kg/m²或更高，或同时接受 SGLT2 抑制剂治疗的 2 型糖尿病成人患者，随机分为每周一次皮下注射 CagriSema、司美格鲁肽或卡格列净（均递增至 2.4mg）。使用交互式网络应答系统进行中心随机分组，根据 SGLT2 抑制剂治疗的使用情况进行分层（是与否）。试验参与者、研究者和试验赞助商工作人员在整个试验过程中均对治疗分配情况进行了设盲。主要终点是从基线到 HbA 的变化；次要终点是体重、空腹血糖、连续血糖监测（CGM）参数和安全性。所有接受随机分组的参与者都进行了疗效分析，所有接受随机分组且至少接受一剂试验药物的参与者都进行了安全性分析。该试验在 ClinicalTrials.gov （NCT04982575）上注册，现已完成。
在 2021 年 8 月 2 日至 10 月 18 日期间，92 名参与者被随机分为 CagriSema 组（n=31）、司美格鲁肽组（n=31）或卡格列净组（n=30）。59 名（64%）参与者为男性；参与者的平均年龄为 58 岁（标准差 9）。从基线到第 32 周时 HbA 的平均变化（CagriSema：-2.2 个百分点[SE 0.15]；司美格鲁肽：-1.8 个百分点[0.16]；卡格列净：-0.9 个百分点[0.15]），CagriSema 组与卡格列净组相比降幅更大（估计治疗差异-1.3 个百分点[95%CI -1.7 至-0.8]；p<0.0001），但与司美格鲁肽组相比降幅无差异（-0.4 个百分点[-0.8 至 0.0]；p=0.075）。从基线到第 32 周时体重的平均变化（CagriSema：-15.6%[SE 1.26]；司美格鲁肽：-5.1%[1.26]；卡格列净：-8.1%[1.23]），CagriSema 组与司美格鲁肽组和卡格列净组相比降幅更大（均 p<0.0001）。从基线到第 32 周时空腹血糖的平均变化（CagriSema：-3.3mmol/L[SE 0.3]；司美格鲁肽：-2.5mmol/L[0.4]；卡格列净：-1.7mmol/L[0.3]），CagriSema 组与卡格列净组相比降幅更大（p=0.0010），但与司美格鲁肽组相比降幅无差异（p=0.10）。基线时 CagriSema、司美格鲁肽和卡格列净组的时间在范围内（3.9-10.0mmol/L）分别为 45.9%、32.6%和 56.9%，第 32 周时分别为 88.9%、76.2%和 71.7%。CagriSema 组、司美格鲁肽组和卡格列净组分别有 21（68%）、22（71%）和 24（80%）名参与者报告了不良事件。最常见的是轻度或中度胃肠道不良事件；未报告 2 级或 3 级低血糖事件。无致命不良事件报告。
在 2 型糖尿病患者中，CagriSema 治疗可显著改善血糖控制（包括 CGM 参数）。与卡格列净相比，CagriSema 治疗使 HbA 的变化更大，但与司美格鲁肽相比则无差异。与司美格鲁肽和卡格列净相比，CagriSema 治疗可显著减轻体重，且耐受性良好。这些数据支持在更长、更大的 3 期研究中进一步评估 CagriSema 在该人群中的应用。
诺和诺德。
