Mossakowski Medical Research Centre, Polish Academy of Sciences and Central Clinical Hospital MSWiA, Warsaw, Poland.
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
Diabetes Obes Metab. 2022 Sep;24(9):1753-1761. doi: 10.1111/dom.14760. Epub 2022 May 30.
To assess cardiovascular, glycaemic, weight and safety outcomes of long-term treatment with dulaglutide 1.5 mg compared with placebo in patients with a baseline HbA1c of less than 7% versus 7% or higher.
Intention-to-treat analyses were performed on REWIND participants with a baseline HbA1c measurement, using Cox proportional hazards regression and mixed model for repeated measures. Subgroup analyses with factors for baseline HbA1c categories and their interaction with treatment group, as well as analyses within the HbA1c subgroups, were conducted. Additionally, sensitivity analyses were performed for baseline HbA1c subgroups of 6.5% or less and more than 6.5%.
Of the 9876 eligible participants, 3921 and 5955 had a baseline HbA1c of less than 7% and 7% or higher, respectively. Mean baseline HbA1c was 6.3% and 8.0% and the mean duration of diabetes was 9.0 and 11.6 years in the respective subgroups. The less than 7% subgroup was slightly older and less frequently insulin-treated. There was no evidence of a differential dulaglutide treatment effect on body mass index (BMI) reduction, cardiovascular or safety outcomes of interest between the baseline HbA1c subgroups. Treatment-by-baseline HbA1c group interaction was significant for HbA1c change from baseline (P < .001), with a greater reduction in the subgroup with higher baseline HbA1c values. Sensitivity analyses by baseline HbA1c subgroups of 6.5% or less and more than 6.5% showed similar results.
The reduced incidence of cardiovascular events, and the reduction in BMI in participants treated with once-weekly dulaglutide, were independent of the baseline HbA1c level. Conversely, participants with a higher baseline HbA1c level had greater reductions in HbA1c. Dulaglutide has a positive benefit-risk profile and can be considered in patients with comparatively well-controlled HbA1c levels seeking optimal metabolic control and cardiovascular benefits.
评估基线糖化血红蛋白（HbA1c）＜7%与≥7%的患者接受度拉鲁肽 1.5mg 治疗与安慰剂相比的心血管、血糖、体重和安全性结局。
在基线 HbA1c 检测的 REWIND 参与者中进行意向治疗分析，采用 Cox 比例风险回归和重复测量混合模型。对基线 HbA1c 分类的因素进行亚组分析，并与治疗组进行交互作用分析，以及在 HbA1c 亚组内进行分析。此外，还对基线 HbA1c＜6.5%和＞6.5%亚组进行了敏感性分析。
在 9876 名合格参与者中，3921 名和 5955 名基线 HbA1c 分别＜7%和≥7%。相应亚组的平均基线 HbA1c 分别为 6.3%和 8.0%，糖尿病平均病程分别为 9.0 和 11.6 年。＜7%亚组年龄稍大，胰岛素治疗频率较低。在基线 HbA1c 亚组之间，没有证据表明度拉鲁肽治疗对体重指数（BMI）降低、心血管或安全性结局有差异。治疗与基线 HbA1c 组之间的交互作用对基线 HbA1c 变化有显著影响（P＜0.001），基线 HbA1c 值较高的亚组降低幅度更大。按基线 HbA1c＜6.5%和＞6.5%亚组进行敏感性分析，结果相似。
每周一次度拉鲁肽治疗参与者的心血管事件发生率降低和 BMI 降低与基线 HbA1c 水平无关。相反，基线 HbA1c 水平较高的患者 HbA1c 降低幅度更大。度拉鲁肽具有良好的获益风险比，可考虑用于 HbA1c 水平控制较好的患者，以寻求最佳代谢控制和心血管获益。
