SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum

IF 3.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics Pub Date : 2024-11-01 DOI:10.1016/j.clinthera.2024.06.021

Frank G. Preston , Matthew Anson , David R. Riley , Gema H. Ibarburu , Alexander Henney , Gregory Y.H. Lip , Daniel J. Cuthbertson , Uazman Alam , Sizheng S. Zhao

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Abstract

Purpose

This study aimed to evaluate the relative association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) with the incidence of gout in patients with type 2 diabetes (T2D) using real-world data.

Methods

We conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation.

Findings

Prior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], P < 0.0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74–0.92], P < 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], P < 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], P < 0.0001).

Implications

In this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population.

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SGLT2抑制剂（而非GLP-1受体激动剂）可降低整个治疗范围内2型糖尿病患者的痛风发病率。

目的：本研究旨在利用真实世界的数据，评估钠-葡萄糖共转运体-2抑制剂（SGLT2i）和胰高血糖素样肽-1受体激动剂（GLP-1Ra）与2型糖尿病（T2D）患者痛风发病率之间的相关性：我们利用 TriNetX（国际联合数据库）的数据开展了一项队列研究。我们纳入了在分析日期前至少 2 年开始使用二甲双胍或胰岛素（无论是单独使用还是与 SGLT2i 或 GLP-1Ra 一起使用）的患者。我们对 26 个相关特征进行了倾向评分匹配 (PSM)（1:1）。我们进行了事件发生时间分析，以评估用药 5 年后痛风、全因死亡率（阳性对照）和带状疱疹感染（阴性对照）的发生率：在 PSM 之前，队列人数如下：二甲双胍对照组 1,111,449 人；SGLT2i 联合二甲双胍 101,706 人；GLP-1Ra 联合二甲双胍 110,180 人；胰岛素对照组 1,398,066 人；SGLT2i 联合胰岛素 68,697 人；GLP-1Ra 联合胰岛素 99,693 人。与二甲双胍对照组相比，SGLT2i 联合二甲双胍治疗 5 年后痛风发病率明显降低（HR 0.75 [95% CI 0.69-0.82]，P < 0.0001）。同样，与胰岛素对照组相比，SGLT2i 联合胰岛素治疗 5 年后痛风发病率也有显著统计学下降（HR 0.83 [95% CI 0.74-0.92]，P < 0.0001）。相反，使用 GLP-1Ra 和匹配对照组之间的痛风发病率没有明显差异。亚组分析显示，在使用二甲双胍（HR 0.77 [95% CI 0.70-0.86]，P < 0.0001）或胰岛素（HR 0.82 [95% CI 0.73-0.91]，P < 0.0001）的组别中，与 GLP-1Ra 相比，使用 SGLT2i 可降低痛风的发病率：在这项大规模真实世界研究中，与胰岛素和二甲双胍对照组相比，使用SGLT2i可降低T2D患者的痛风发病率。这些研究结果表明，SGLT2i 有可能成为治疗这类人群痛风的一种有前途的治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical therapeutics 医学-药学

CiteScore

6.00

自引率

3.10%

发文量

154

审稿时长

9 weeks

期刊介绍： Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.