The effect of once-weekly insulin icodec vs once-daily basal insulin on physical activity-attributed hypoglycaemia in type 2 diabetes: a post hoc analysis of ONWARDS 1-5.

Once-weekly basal insulins may elevate the risk of physical activity-attributed hypoglycaemia compared with other basal insulins because the administered levels cannot be reduced in anticipation of increased physical activity.

与其它基础胰岛素相比，每周一次的基础胰岛素可能会增加体力活动相关的低血糖风险，因为无法在预期体力活动增加时降低给药水平。

This post hoc analysis of five separate randomised trials (ONWARDS 1-5) aimed to examine physical activity-attributed hypoglycaemic episodes in adults with type 2 diabetes receiving either once-weekly basal insulin icodec (herein referred to as 'icodec') or once-daily basal insulins.

这项对五项独立随机试验（ONWARDS 1-5）的事后分析旨在检查在每周一次基础胰岛素icodec（以下简称'icodec'）或每天一次基础胰岛素治疗的2型糖尿病成人中，因体力活动导致的低血糖事件。

Methods

The ONWARDS 1-5 Phase 3a randomised controlled trials compared the efficacy and safety of once-weekly basal icodec vs once-daily basal insulin in insulin-naive (ONWARDS 1, 3 and 5) and insulin-experienced (ONWARDS 2 and 4) adults with type 2 diabetes.

ONWARDS 1-5第三阶段a随机对照试验比较了每周一次基础胰岛素icodec与每天一次基础胰岛素在胰岛素未使用（ONWARDS 1、3和5）和胰岛素使用经验（ONWARDS 2和4）的2型糖尿病成人中的疗效和安全性。

Participants self-monitored their blood glucose levels using a blood glucose meter and a digital diary.

参与者使用血糖仪和数字日记自我监测他们的血糖水平。

In each trial, suspected hypoglycaemia symptoms triggered additional self-measured blood glucose readings, and values indicative of hypoglycaemia were recorded in the participants' digital diary.

在每次试验中，疑似低血糖症状触发了额外的自我测量血糖读数，低血糖指示值被记录在参与者的数字日记中。

Participants who experienced hypoglycaemic episodes were instructed to note any relation of each episode to physical activity.

经历低血糖发作的参与者被指示记录每次发作与体力活动的关联。

Hypoglycaemic episodes were classified as alert value (level 1: blood glucose <3.9 but ≥3.0 mmol/l), clinically significant (level 2: blood glucose <3.0 mmol/l) or severe (level 3: cognitive impairment requiring external assistance).

低血糖发作被分类为警戒值（1级：血糖<3.9但≥3.0毫摩尔/升）、临床显著（2级：血糖<3.0毫摩尔/升）或严重（3级：认知障碍需要外部帮助）。

The proportions of hypoglycaemic episodes that were attributed to physical activity and the ORs of having a physical activity-attributed hypoglycaemic episode were calculated for the two basal insulin types (once-weekly vs once-daily) for each of the five trials.

在五项试验中，计算了两种基础胰岛素（每周一次与每日一次）导致的低血糖发作中，归因于体力活动的比例以及发生体力活动相关低血糖发作的比值比（ORs）。

Results

Across all trials, there were no consistent differences between icodec and the once-daily insulin comparators in the proportions of hypoglycaemic episodes that were attributed to physical activity; these episodes were mainly alert value or clinically significant hypoglycaemic episodes.

在所有试验中，icodec与每日一次胰岛素对照组在归因于体力活动的低血糖发作比例上没有显著差异；这些发作主要是警戒值或临床显著的低血糖发作。

In both insulin-naive and insulin-experienced participants, the incidenceof physical activity-attributed clinically significant or severe hypoglycaemic episodes was consistently ≤3.0% in ONWARDS 1, 2, 3 and 5.

在ONWARDS 1、2、3和5研究中，无论是胰岛素未使用者还是胰岛素使用者，体力活动引起的临床显著或严重低血糖事件的发生率始终≤3.0%。

In ONWARDS 4, the incidenceof physical activity-attributed hypoglycaemic episodes was numerically higher in both treatment groups (18.6% [icodec] vs 17.9% [insulin glargine U100]), which was expected given the basal-bolus insulin regimen.

在ONWARDS 4研究中，体力活动引起的低血糖事件的发生率在两种治疗组中均数值上较高（18.6% [icodec] vs 17.9% [胰岛素格拉珍U100]），这与基础-餐后胰岛素治疗方案是一致的预期结果。

Across all trials, there were no statistically significant differences in the odds of experiencing a physical activity-attributed clinically significant or severe hypoglycaemic episode with icodec vs once-daily insulin comparators.

在所有试验中，与每日一次胰岛素对照组相比，使用icodec治疗的患者经历与体力活动相关的临床显著或严重低血糖事件的几率没有统计学上的显著差异。

The frequency of recurrent clinically significant or severe hypoglycaemic episodes in the 24 h after a physical activity-attributed clinically significant or severe hypoglycaemic episode was low, with no such episodes in ONWARDS 1, 3 and 5.

在体力活动相关的临床显著或严重低血糖事件发生后的24小时内，再次发生临床显著或严重低血糖事件的频率较低，在ONWARDS 1、3和5试验中没有此类事件。

In contrast, in ONWARDS 2 and 4, the frequency of recurrent clinically significant hypoglycaemic episodes in the 24 h after a physical activity-attributed clinically significant or severe hypoglycaemic episode was numerically higher with icodec vs the once-daily insulin comparators, whilst no additional severe episodes were reported in any participants across the trials.

相比之下，在ONWARDS 2和4研究中，与每日一次的胰岛素对照组相比，身体活动后24小时内复发的临床显著或严重低血糖事件的频率在使用icodec的患者中数值上更高，尽管在任何试验中都没有报告额外的严重事件。

conclusions/interpretation

These findings do not suggest that there is an additional increase in hypoglycaemia risk attributed to physical activity with once-weekly basal icodec vs once-daily basal insulins in adults with type 2 diabetes.

这些发现并不表明，在2型糖尿病成人中，与每日一次的基础胰岛素相比，每周一次的基础胰岛素icodec会增加与身体活动相关的低血糖风险。

trial_registration

ClinicalTrials.gov NCT04460885 (ONWARDS 1), NCT04770532 (ONWARDS 2), NCT04795531 (ONWARDS 3), NCT04880850 (ONWARDS 4) and NCT04760626 (ONWARDS 5).

ClinicalTrials.gov NCT04460885 (ONWARDS 1), NCT04770532 (ONWARDS 2), NCT04795531 (ONWARDS 3), NCT04880850 (ONWARDS 4) 和 NCT04760626 (ONWARDS 5).