胰高血糖素样肽-1 受体激动剂与二肽基肽酶-4 抑制剂和糖尿病心血管预后与血糖控制效果的关系。一项丹麦全国性研究。

IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Journal of Diabetes Pub Date : 2024-05-16 DOI:10.1111/1753-0407.13560
Bochra Zareini, Katrine Kold Sørensen, Ulrik Pedersen-Bjergaard, Emil Loldrup Fosbøl, Lars Køber, Christian Torp-Pedersen
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引用次数: 0

摘要

目的:根据糖化血红蛋白(HbA1c)达到的目标水平,比较胰高血糖素样肽-1 受体激动剂(GLP-1 RA)与二肽基肽酶-4 抑制剂(DPP-4i)的心血管预防效果:我们利用丹麦的回顾性登记,纳入了 2007 年至 2021 年间已经接受二甲双胍治疗并开始服用 GLP-1 RA 或 DPP-4i 的 2 型糖尿病患者。患者在接受 GLP-1 RA 或 DPP-4i 治疗 6 个月后被纳入。收集纳入前最后一次可用的 HbA1c 测量值。达到的 HbA1c 水平按照低于或高于 53 mmol/mol(7%)的目标水平进行分类。主要结果是非致死性心肌梗死、非致死性中风和全因死亡的复合结果。与 DPP-4i 使用者相比,我们使用多变量 Cox 比例危险模型来估计 HbA1c 水平对 GLP-1 RA 使用者预后的影响:研究纳入了 13 634 名 GLP-1 RA 使用者(中位年龄 56.9 岁,四分位数间距 [IQR]:48.5-65.5;53% 为男性)和 39 839 名 DPP-4i 使用者(中位年龄 63.4 岁,四分位数间距 [IQR]:54.6-71.8;61% 为男性)。根据达到的 HbA1c 水平,GLP-1 RA 和 DPP-4i 用户数量如下:HbA1c ≤ 53 mmol/mol (≤ 7.0%):3026(22%)对 4824(12%);HbA1c > 53 mmol/mol(>7.0%):6577(48%)对 17 508(44%);HbA1c 缺失:4031(30%)对 17 507(44%)。在中位随访 5 年(IQR:2.6-5.0)期间,954 名 GLP-1 RA 使用者与 7093 名 DPP-4i 使用者相比出现了主要结果。根据 HbA1c 分类,GLP1-RA 与 DPP-4i 的 5 年相关结果风险(95% 置信区间 [CI])如下:HbA1c ≤ 53 mmol/mol:10.3%(8.2-12.3)对 24.3%(22.7-25.8);HbA1c > 53 mmol/mol:16.0%(14.3-17.6)对 21.1%(20.3-21.9);HbA1c 缺失:17.1%(15.7-18.5)对 25.6%(24.9-26.3)。当达到较低的 HbA1c 水平时,GLP-1 RA 相对于 DPP-4i 的预防效果明显增强:HbA1c ≤ 53 mmol/mol:0.65 (0.52-0.80);HbA1c > 53 mmol/mol:0.92 (0.83-1.03);HbA1c 缺失:0.92 (0.84-1.02)(交互作用的 p 值 结论:GLP-1 RA 与 DPP-4i 的预防效果相关:使用 GLP-1 RA 可降低主要不良心血管后果的发生率。达到目标血糖水平的患者的相关性更强,而未达到目标血糖水平的患者的相关性较弱,这表明达到的 HbA1c 水平与 GLP-1 RA 之间存在相互作用。
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Glucagon-like-peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes in diabetes in relation to achieved glycemic control. A Danish nationwide study

Aim

To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c).

Methods

We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users.

Results

The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5–65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6–71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6–5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2–12.3) versus 24.3% (22.7–25.8); HbA1c > 53 mmol/mol: 16.0% (14.3–17.6) versus 21.1% (20.3–21.9); missing HbA1c: 17.1% (15.7–18.5) versus 25.6% (24.9–26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52–0.80); HbA1c > 53 mmol/mol: 0.92 (0.83–1.03); missing HbA1c: 0.92 (0.84–1.02) (p value for interaction <.001).

Conclusion

GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA.

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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
期刊最新文献
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