Ma Kevin Sheng-Kai, Lo Jui-En, Kyttaris Vasileios C, Tsokos George C, Costenbader Karen H
Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Division of Rheumatology and Clinical Immunology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Arthritis Rheumatol. 2025 Apr;77(4):414-422. doi: 10.1002/art.43037. Epub 2024 Dec 5.
Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D).
We performed an emulated clinical trial in an insurance-based cohort in the United States, evaluating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PSs) based on clinical and demographic factors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox models.
Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 95% CI 0.50-0.76), end-stage renal disease (HR 0.40, 95% CI 0.20-0.80), heart failure (HR 0.72, 95% CI 0.56-0.92), emergency department visits (HR 0.90, 0.82-0.99), and severe sepsis (HR 0.61, 95% CI 0.39-0.94). Risks of all-cause mortality (HR 0.89, 95% CI 0.65-1.21), lupus nephritis (HR 0.67, 95% CI 0.38-1.15), myocardial infarction (HR 0.81, 95% CI 0.54-1.23), stroke (HR 1.03, 95% CI 0.74-1.44), and hospitalizations (HR 0.76, 95% CI 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 95% CI 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 95% CI 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.07, 95% CI 0.53-2.14) and fractures (HR 0.95, 95% CI 0.66-1.36).
In this emulated clinical trial, treatment with SGLT2i, compared to DPP4i therapy, was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.
系统性红斑狼疮（SLE）患者被排除在钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）的临床试验之外。目前尚不清楚SGLT2i对心脏和肾脏的益处是否也适用于患有SLE合并2型糖尿病（T2D）的患者。
我们在美国一个基于保险的队列中进行了一项模拟临床试验，评估SGLT2i与二肽基肽酶-4抑制剂（DPP4i）在预防SLE合并T2D患者的心血管、肾脏和其他临床结局方面的效果。根据临床和人口统计学因素，使用倾向评分（PS）将开始使用SGLT2i的患者与开始使用DPP4i的患者进行匹配。使用Cox模型计算风险比（HR）及95%置信区间（CI）。
比较了2165例开始使用SGLT2i的患者和2165例PS匹配的开始使用DPP4i的患者的结局。在平均753.1（±479.2）天的时间里，接受SGLT2i治疗的患者发生急性肾损伤（HR 0.49，95%CI 0.39-0.63）、慢性肾病（HR 0.61，95%CI 0.50-0.76）、终末期肾病（HR 0.40，95%CI 0.20-0.80）、心力衰竭（HR 0.72，95%CI 0.56-0.92）、急诊就诊（HR 0.90，0.82-0.99）和严重脓毒症（HR 0.61，95%CI 0.39-0.94）的风险显著降低。全因死亡率（HR 0.89，95%CI 0.65-1.21）、狼疮性肾炎（HR 0.67，95%CI 0.38-1.15）、心肌梗死（HR 0.81，95%CI 0.54-1.23）、中风（HR 1.03，95%CI 0.74-1.44）和住院（HR 0.76，95%CI 0.51-1.12）的风险没有差异。生殖器感染风险（HR 1.31，95%CI 1.07-1.61）增加，但尿路感染风险（HR 0.90，95%CI 0.79-1.03）没有差异。糖尿病酮症酸中毒风险（HR 1.07，95%CI 0.53-2.14）和骨折（HR 0.95，95%CI 0.66-1.36）没有显著差异。
在这项模拟临床试验中，与DPP4i治疗相比，SGLT2i治疗与SLE合并T2D患者的几种心脏和肾脏并发症风险显著降低相关。
