Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Emergency Department, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.
Acta Diabetol. 2022 May;59(5):697-709. doi: 10.1007/s00592-021-01841-4. Epub 2022 Feb 3.
To gain insights on the cardiovascular effects of metformin and sulphonylurea, the present study compares the rates of incident atrial fibrillation, stroke, cardiovascular mortality and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus.
This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1, 2000, and December 31, 2019. The primary outcome was new-onset AF or stroke. Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, past comorbidities and medication use. Cox regression was used to identify significant risk factors. Competing risk analysis was conducted using cause-specific and subdistribution hazard models. Sensitivity analyses using propensity score stratification, high-dimensional propensity score and inverse probability of treatment weighting were conducted. Subgroup analyses were conducted for age and gender in the matched cohort.
A total of 36,228 sulphonylurea users and 72,456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% confidence interval [CI]: 2.75-3.77; P < 0.0001), stroke (HR: 3.23, 95% CI: 3.01-3.45; P < 0.0001), cardiovascular mortality (HR: 3.60, 95% CI: 2.62-4.81; P < 0.0001) and all-cause mortality (HR: 4.35, 95% CI: 3.16-4.75; P < 0.0001) compared to metformin users. Similarly, significant results were observed using cause-specific and subdistribution hazard models. Sensitivity analysis using techniques based on the propensity score also yielded similar results.
Sulphonylurea use was associated with higher risks of incident AF, stroke, cardiovascular mortality and all-cause mortality compared to metformin. Males and patients older than 65 years with sulphonylurea use were exposed to the highest risks.
为了深入了解二甲双胍和磺脲类药物对心血管的影响，本研究比较了 2 型糖尿病患者使用二甲双胍和磺脲类药物的心房颤动、中风、心血管死亡率和全因死亡率的发生率。
这是一项回顾性基于人群的 2 型糖尿病患者队列研究，纳入了 2000 年 1 月 1 日至 2019 年 12 月 31 日期间接受磺脲类或二甲双胍单药治疗的患者。主要结局是新发房颤或中风。次要结局为心血管、非心血管和全因死亡率。根据人口统计学特征、CHA-DS-VASc 评分、既往合并症和药物使用情况，对磺脲类和二甲双胍使用者进行倾向评分匹配（1:2 比例）。使用 Cox 回归识别显著风险因素。使用特定原因和亚分布风险模型进行竞争风险分析。使用倾向评分分层、高维倾向评分和治疗反概率加权进行敏感性分析。在匹配队列中进行了年龄和性别亚组分析。
共纳入 36228 例磺脲类使用者和 72456 例二甲双胍使用者进行倾向评分匹配队列分析。多变量 Cox 回归显示，磺脲类使用者新发房颤的风险较高（风险比[HR]：2.89，95%置信区间[CI]：2.75-3.77；P<0.0001）、中风（HR：3.23，95%CI：3.01-3.45；P<0.0001）、心血管死亡率（HR：3.60，95%CI：2.62-4.81；P<0.0001）和全因死亡率（HR：4.35，95%CI：3.16-4.75；P<0.0001）均高于二甲双胍使用者。同样，使用特定原因和亚分布风险模型也观察到了显著结果。基于倾向评分的敏感性分析也得到了类似的结果。
与二甲双胍相比，磺脲类药物的使用与新发房颤、中风、心血管死亡率和全因死亡率风险增加相关。使用磺脲类药物的男性和年龄大于 65 岁的患者风险最高。
