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钠-葡萄糖协同转运蛋白 2 抑制剂用于 2 型糖尿病与台湾地区痛风发病的相关性。

Association of Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and Incidence of Gout in Taiwan.

机构信息

Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

PhD Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.

出版信息

JAMA Netw Open. 2021 Nov 1;4(11):e2135353. doi: 10.1001/jamanetworkopen.2021.35353.

Abstract

IMPORTANCE

The use of sodium-glucose transport protein 2 (SGLT2) inhibitors is currently a standard intervention in patients with type 2 diabetes (T2DM) and exerts favorable pleiotropic effects to consistently lower blood urate levels. However, to date, no association between SGLT2 inhibitor use and the incidence of gout have been established.

OBJECTIVE

To investigate whether prescribed SGLT2 inhibitors are associated with lower gout incidence in patients with T2DM.

DESIGN, SETTING, AND PARTICIPANTS: In a cohort study, all patients with incident T2DM in Taiwan National Health Institution databases between May 1, 2016, and December 31, 2018, were retrospectively analyzed. As a comparator, patients using dipeptidyl peptidase 4 (DPP4) inhibitors were included. A total of 47 905 individuals receiving an SGLT2 inhibitor and 183 303 receiving a DPP4 inhibitor were evaluated, along with 47 405 pairs of patients using an SGLT2 inhibitor or DPP4 inhibitor in 1:1 propensity score-matched analyses. Data analysis was conducted from April 1 to June 30, 2021.

MAIN OUTCOMES AND MEASURES

A gout diagnosis was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Multiple Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs.

RESULTS

In total, 231 208 patients with T2DM were included in the population; 113 812 individuals (49.22%) were women, and the mean (SD) age was 61.53 (12.86) years. The overall gout incidence was 20.26 per 1000 patient-years for SGLT2 inhibitor users and 24.30 per 1000 patient-years for DPP4 inhibitor users. When potential risk factors were adjusted in the propensity score-matched population, use of SGLT2 inhibitors was associated with a lower risk of gout (HR, 0.89; 95% CI, 0.82-0.96) compared with DPP4 inhibitors, particularly for patients receiving dapagliflozin (HR, 0.86; 95% CI, 0.78-0.95). A sensitivity analysis, performed when a gout diagnosis was ascertained using the ICD-9-CM or ICD-10-CM code with gout-related medication, also showed a significantly lower risk for gout incidence of 15% with SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74-0.97). Subgroup analysis indicated that SGLT2 inhibitor benefits in patients with T2DM to achieve a lower gout risk were not different across subgroups.

CONCLUSIONS AND RELEVANCE

The findings of this study suggest that patients with T2DM who are receiving SGLT2 inhibitors may have a lower risk for gout compared with those receiving DPP4 inhibitors.

摘要

重要性

目前,钠-葡萄糖协同转运蛋白 2(SGLT2)抑制剂的使用是 2 型糖尿病(T2DM)患者的标准干预措施,并具有有利的多效性作用,可持续降低血尿酸水平。然而,迄今为止,尚未确定 SGLT2 抑制剂的使用与痛风的发生之间存在关联。

目的

研究在 T2DM 患者中,处方 SGLT2 抑制剂是否与较低的痛风发病率相关。

设计、设置和参与者:在一项队列研究中,对 2016 年 5 月 1 日至 2018 年 12 月 31 日期间在台湾国家卫生机构数据库中发生 T2DM 的所有患者进行回顾性分析。作为对照,纳入使用二肽基肽酶 4(DPP4)抑制剂的患者。共评估了 47905 名接受 SGLT2 抑制剂和 183303 名接受 DPP4 抑制剂的患者,以及在 1:1 倾向评分匹配分析中接受 SGLT2 抑制剂或 DPP4 抑制剂的 47405 对患者。数据分析于 2021 年 4 月 1 日至 6 月 30 日进行。

主要结局和测量

痛风的诊断基于国际疾病分类,第 9 修订版,临床修正(ICD-9-CM)和国际疾病分类,第 10 修订版,临床修正(ICD-10-CM)。使用多 Cox 比例风险回归模型计算风险比(HR)和 95%CI。

结果

共有 231208 名 T2DM 患者纳入人群;113812 名(49.22%)为女性,平均(SD)年龄为 61.53(12.86)岁。SGLT2 抑制剂使用者的总体痛风发病率为 20.26/1000 患者年,DPP4 抑制剂使用者为 24.30/1000 患者年。在倾向评分匹配人群中调整潜在风险因素后,与 DPP4 抑制剂相比,使用 SGLT2 抑制剂与较低的痛风风险相关(HR,0.89;95%CI,0.82-0.96),尤其是使用达格列净的患者(HR,0.86;95%CI,0.78-0.95)。当使用 ICD-9-CM 或 ICD-10-CM 代码和痛风相关药物确定痛风诊断的敏感性分析也显示 SGLT2 抑制剂可使痛风发病率降低 15%,风险显著降低(HR,0.85;95%CI,0.74-0.97)。亚组分析表明,在 T2DM 患者中,SGLT2 抑制剂可降低痛风风险的获益在不同亚组之间没有差异。

结论和相关性

这项研究的结果表明,与接受 DPP4 抑制剂的患者相比,接受 SGLT2 抑制剂的 T2DM 患者发生痛风的风险可能较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b099/8605485/4bbd26af3264/jamanetwopen-e2135353-g001.jpg

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