Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.

Methods

This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions.

这项为期52周的随机、多中心、开放标签、平行组、IIIa期试验在13个国家/地区的121个地点进行。

Adults with type 2 diabetes (HbA1c 53.0-85.8 mmol/mol [7.0-10.0%]) receiving GLP-1 RA therapy with or without additional oral glucose-lowering medications were randomly assigned 1:1 to once-weekly IcoSema or once-weekly semaglutide 1.0 mg.

接受GLP-1 RA治疗（可能伴有额外的口服降糖药物）的2型糖尿病成人（HbA1c 53.0-85.8 mmol/mol [7.0-10.0%]）被随机1:1分配至每周一次的IcoSema或每周一次的semaglutide 1.0 mg治疗。

The primary endpoint was change in HbA1c from baseline to week 52; superiority of IcoSema to semaglutide 1.0 mg was assessed.

主要终点是基线至第52周HbA1c的变化；评估了IcoSema相对于semaglutide 1.0 mg的优势。

Secondary endpoints included change in fasting plasma glucose and body weight (baseline to week 52), and combined clinically significant (level 2; <3.0 mmol/l) or severe (level 3; associated with severe cognitive impairment requiring external assistance for recovery) hypoglycaemia (baseline to week 57).

次要终点包括空腹血糖和体重的变化（从基线到第52周），以及结合临床上显著（2级；<3.0 mmol/l）或严重（3级；与严重认知障碍相关，需要外部帮助才能恢复）的低血糖事件（从基线到第57周）。

Results

Overall, 683 participants were randomised using a Randomisation and Trial Supply Management system to IcoSema (n=342) or semaglutide 1.0 mg (n=341).

总体而言，683名参与者使用随机化和试验供应管理系统随机分配到IcoSema组（n=342）或semaglutide 1.0 mg组（n=341）。

Mean ± SD baseline characteristics were as follows: HbA1c 64.0±8.2 mmol/mol (8.0±0.7%); diabetes duration 12.6±6.9 years; and BMI 31.1±4.7 kg/m2.

基线特征的平均值±标准差如下：HbA1c为64.0±8.2毫摩尔/摩尔（8.0±0.7%）；糖尿病病程为12.6±6.9年；BMI为31.1±4.7千克/平方米。

From baseline to week 52, mean change in HbA1c was -14.7 mmol/mol (-1.35%-points) in the IcoSema group and -9.88 mmol/mol (-0.90%-points) in the semaglutide group; the estimated treatment difference (ETD) was -4.85 (95% CI -6.13, -3.57) mmol/mol (-0.44 [95% CI -0.56, -0.33]%-points), confirming superiority of IcoSema to semaglutide (p<0.0001).

从基线到第52周，IcoSema组的HbA1c平均变化为-14.7毫摩尔/摩尔（-1.35百分点），semaglutide组为-9.88毫摩尔/摩尔（-0.90百分点）；估计的治疗差异（ETD）为-4.85（95%置信区间-6.13, -3.57）毫摩尔/摩尔（-0.44 [95%置信区间-0.56, -0.33]百分点），证实了IcoSema对semaglutide的优越性（p<0.0001）。

The estimated mean change in fasting plasma glucose from baseline to week 52 was statistically significantly reduced with IcoSema vs semaglutide (-2.48 mmol/l vs -1.43 mmol/l, respectively; ETD -1.05 [95% CI -1.36, -0.75] mmol; p<0.0001).

从基线到第52周，IcoSema与semaglutide相比，空腹血浆葡萄糖的估计平均变化显著降低（分别为-2.48 mmol/l和-1.43 mmol/l；ETD -1.05 [95% CI -1.36, -0.75] mmol；p<0.0001）。

Mean change in body weight from baseline to week 52 was statistically significantly different between groups: +0.84 kg for IcoSema vs -3.70 kg for semaglutide (ETD 4.54 kg [95% CI 3.84, 5.23]; p<0.0001).

从基线到第52周，两组间体重的平均变化存在统计学上的显著差异：IcoSema组为+0.84 kg，而semaglutide组为-3.70 kg（ETD 4.54 kg [95% CI 3.84, 5.23]；p<0.0001）。

There was no statistically significant difference in the rate of combined clinically significant or severe hypoglycaemia between IcoSema and semaglutide (0.042 vs 0.036 episodes per person-year of exposure; estimated rate ratio 1.20 [95% CI 0.53, 2.69]; p=0.66).

在 IcoSema 和 semaglutide 之间，合并临床显著或严重低血糖的发生率没有统计学上的显著差异（每暴露人年发生率分别为0.042和0.036次；估计的比率比为1.20 [95% 置信区间 0.53, 2.69]；p=0.66）。

The proportion of participants experiencing gastrointestinal adverse events was similar between treatment groups (IcoSema 31.4%; semaglutide 34.4%).

治疗组之间经历胃肠道不良事件的参与者比例相似（IcoSema 31.4%；semaglutide 34.4%）。

conclusions/interpretation

In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema in comparison with once-weekly semaglutide 1.0 mg demonstrated superiority in HbA1c reduction, similar rates of clinically significant or severe hypoglycaemia, and similar frequency of gastrointestinal adverse events.

在那些使用GLP-1 RA治疗但血糖控制不佳的2型糖尿病患者中，无论是否联合使用其他口服降糖药物，与每周一次的1.0 mg司美格鲁肽相比，每周一次的IcoSema显示出在降低HbA1c方面的优越性，临床显著或严重低血糖的发生率相似，胃肠道不良事件的发生频率也相似。

However, weight change from baseline to week 52 was statistically significantly in favour of semaglutide 1.0 mg.

然而，从基线到第52周，体重的变化在统计学上显著有利于1.0 mg司美格鲁肽。

trial_registration

ClinicalTrials.gov NCT05259033 FUNDING: This trial was funded by Novo Nordisk.

临床试验注册号NCT05259033 资助信息：本试验由诺和诺德公司资助。