Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, 100, Taiwan.
Sci Rep. 2021 Jun 11;11(1):12400. doi: 10.1038/s41598-021-91902-z.
This retrospective cohort study used the nationwide database of Taiwan's National Health Insurance to investigate whether metformin would reduce the risk of acute appendicitis in patients with type 2 diabetes mellitus. We first identified 423,949 patients newly diagnosed of diabetes from 1999 to 2005. After excluding patients having type 1 diabetes mellitus, missing data, previous history of acute appendicitis, aged < 15 years, aged > 80 years and followed up for < 6 months, 338,172 ever users and 21,861 never users of metformin were followed up from January 1, 2006 until December 31, 2011. Incidence of acute appendicitis was estimated for never users, ever users and subgroups (divided by median, tertiles and quartiles, respectively) of dose-response indicators including cumulative duration (months), cumulative dose (mg) and average daily dose (mg/day) of metformin therapy. We used Cox regression incorporated with the inverse probability of treatment weighting using propensity score to estimate the overall hazard ratio for ever versus never users, and the hazard ratios for subgroups of dose-response indicators versus never users. Results showed that new-onset acute appendicitis was diagnosed in 1558 ever users and 179 never users during follow-up. The incidence was 98.15 per 100,000 person-years in ever users and was 189.48 per 100,000 person-years in never users. The overall hazard ratio (95% confidence interval) of 0.514 (0.441-0.600) suggested a lower risk of acute appendicitis associated with metformin use. A dose-response pattern was consistently observed in the analyses of different subgroups of dose-response indicators and the reduced risk associated with metformin use was consistently observed in various sensitivity analyses. An average daily dose of 1000-1500 mg/day can significantly reduce the risk by > 50%. The benefit did not differ between different formulations of metformin, and the estimated hazard ratio for conventional/immediate-release metformin versus never users was 0.516 (0.441-0.603) and was 0.509 (0.421-0.615) for prolonged/slow-release metformin versus never users. It is concluded that metformin use is associated with a reduced risk of acute appendicitis in patients with type 2 diabetes mellitus.
本回顾性队列研究利用台湾全民健康保险数据库，调查二甲双胍是否会降低 2 型糖尿病患者急性阑尾炎的风险。我们首先从 1999 年至 2005 年确定了 423949 例新诊断的糖尿病患者。排除 1 型糖尿病、缺失数据、既往急性阑尾炎病史、年龄<15 岁、年龄>80 岁以及随访时间<6 个月的患者后，共有 338172 例二甲双胍既往使用者和 21861 例从未使用者从 2006 年 1 月 1 日至 2011 年 12 月 31 日进行随访。从未使用者、既往使用者以及累积剂量（月）、累积剂量（mg）和平均日剂量（mg/天）的剂量反应指标中位数、三分位数和四分位数的亚组中估计急性阑尾炎的发生率。我们使用 Cox 回归，结合倾向性评分的逆概率治疗加权，估计了二甲双胍治疗与从未使用者相比的总体危险比（HR），以及剂量反应指标的亚组与从未使用者相比的 HR。结果显示，在随访期间，1558 例既往使用者和 179 例从未使用者被诊断为新发急性阑尾炎。既往使用者的发病率为每 100000 人年 98.15 例，从未使用者的发病率为每 100000 人年 189.48 例。总体 HR（95%置信区间）为 0.514（0.441-0.600），提示二甲双胍的使用与急性阑尾炎风险降低有关。在不同剂量反应指标亚组的分析中观察到一致的剂量反应模式，并且在各种敏感性分析中观察到与二甲双胍使用相关的风险降低是一致的。平均日剂量为 1000-1500mg/天可显著降低 50%以上的风险。不同剂型的二甲双胍之间的获益没有差异，与从未使用者相比，常规/速释二甲双胍的估计 HR 为 0.516（0.441-0.603），而缓释/控释二甲双胍的估计 HR 为 0.509（0.421-0.615）。研究结论为，二甲双胍的使用与 2 型糖尿病患者急性阑尾炎风险降低有关。
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