近日，韩国成均馆大学Ju-Young Shin团队研究了钠葡萄糖协同转运蛋白2抑制剂与自身免疫性风湿性疾病风险：基于人群的队列研究。相关论文发表在2025年10月15日出版的《英国医学杂志》上。

为了评估钠-葡萄糖共转运蛋白-2 （SGLT-2）抑制剂的使用和成人2型糖尿病自身免疫性风湿疾病的风险，研究组进行了一项回顾性队列研究，使用韩国全国医疗保健数据库2012-2022年的数据，共包括2032157名年龄≥18岁的2型糖尿病患者：552065人开始服用SGLT-2抑制剂，1480092人开始服用磺脲类药物。

主要结局是自身免疫性风湿性疾病，使用一种经过验证的算法，结合诊断代码和在特定疾病的全国性规划中登记来定义。次要结局是个体类型的自身免疫性风湿病，包括炎症性关节炎和结缔组织疾病。生殖器感染和带状疱疹分别用作阳性和阴性对照结果，以评估残留混杂因素。在基于倾向评分的归一化逆概率治疗加权后，估计了每10万人年的危险比和比率差异。

经过倾向评分加权后，该研究共纳入1030088名SGLT-2抑制剂初始使用者（平均年龄58.5岁；男性占59.9%）和1002069名磺脲类药物初始使用者（平均年龄58.5岁；男性占60.1%）。SGLT-2抑制剂与磺脲类药物使用者的加权发病率分别为每10万人年51.90例和58.41例。在中位9个月的随访期间，与磺脲类药物相比，SGLT-2抑制剂可使自身免疫性风湿性疾病发生风险降低11%（风险比0.89（95%置信区间0.81至0.98）；率差为每10万人年-6.50例（95%置信区间-11.86至-1.14）。按年龄、性别、SGLT-2抑制剂类型、基线心血管疾病和肥胖状态分层的亚组分析结果总体一致。对照结局的风险比分别为：生殖器感染2.78（2.72至2.83），带状疱疹1.03（1.01至1.05）。

在这一大型2型糖尿病成人队列中，与磺脲类药物相比，SGLT-2抑制剂与自身免疫性风湿性疾病的风险降低11%有关。这些结果表明，SGLT-2抑制剂可能有助于降低自身免疫性疾病的风险。然而，应仔细权衡这一潜在益处与已知的不良事件和对耐受性的担忧。在其他人群和环境中的复制，以及在现有自身免疫性风湿性疾病患者中的研究，都有必要证实和扩展这些观察结果。

附：英文原文

Title: Sodium-glucose cotransporter-2 inhibitors and risk of autoimmune rheumatic diseases: population based cohort study

Author: Bin Hong, Hyesung Lee, Kyungyeon Jung, Sang Youl Rhee, Dong Keon Yon, Ju-Young Shin

Issue&Volume: 2025/10/15

Abstract:

Objective To evaluate the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and risk of autoimmune rheumatic diseases in adults with type 2 diabetes.

Design Retrospective cohort study.

Setting Nationwide healthcare database in South Korea, 2012-22.

Participants 2032157 adults aged ≥18 years with type 2 diabetes: 552065 initiated SGLT-2 inhibitors and 1480092 initiated sulfonylureas.

Main outcome measures The primary outcome was autoimmune rheumatic disease, defined using a validated algorithm incorporating diagnostic codes and registration in a disease specific nationwide programme. Secondary outcomes were individual types of autoimmune rheumatic diseases, including inflammatory arthritis and connective tissue diseases. Genital infections and herpes zoster were used as positive and negative control outcomes, respectively, to evaluate residual confounding. Hazard ratios and rate differences per 100000 person years were estimated after normalised inverse probability treatment weighting based on propensity score.

Results After propensity score weighting, 1030088 initiators of SGLT-2 inhibitors (mean age 58.5 years; 59.9% men) and 1002069 initiators of sulfonylurea (mean age 58.5 years; 60.1% men) were included in the analysis. The weighted incidence rate per 100000 person years was 51.90 and 58.41 in individuals initiating SGLT-2 inhibitors and sulfonylureas, respectively. Over a median of nine months’ follow-up, SGLT-2 inhibitors were associated with an 11% lower risk of incident autoimmune rheumatic diseases compared with sulfonylureas (hazard ratio 0.89 (95% confidence interval (CI) 0.81 to 0.98); rate difference 6.50 (95% CI 11.86 to 1.14) per 100000 person years). Findings were overall consistent among subgroups stratified by age, sex, type of SGLT-2 inhibitor, baseline cardiovascular disease, and obesity status. The hazard ratios for the control outcomes were 2.78 (2.72 to 2.83) for genital infections and 1.03 (1.01 to 1.05) for herpes zoster.

Conclusions In this large cohort of adults with type 2 diabetes, SGLT-2 inhibitors were associated with an 11% lower risk of autoimmune rheumatic diseases compared with sulfonylureas. These results suggest that SGLT-2 inhibitors may contribute to reducing the risk of autoimmune diseases. This potential benefit, however, should be carefully weighed against known adverse events and concerns about tolerability. Replication in other populations and settings, as well as studies in patients with existing autoimmune rheumatic diseases, are warranted to confirm and extend these observations.

DOI: 10.1136/bmj-2025-085196

Source: https://www.bmj.com/content/391/bmj-2025-085196