Tsur Anat, Leibowitz Gil, Cohen Matan J, Cahn Avivit, Pollack Rena
Department of Endocrinology and Metabolism, Clalit Health Services, Jerusalem, Israel.
The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Diabetes Obes Metab. 2025 Sep;27(9):4989-4997. doi: 10.1111/dom.16545. Epub 2025 Jun 19.
To identify predictors of diabetic ketoacidosis (DKA) in patients with an insulin-deficient phenotype initiating sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy.
This retrospective cohort study analysed data from 31 900 patients with diabetes aged 18-70 identified as having an insulin-deficient phenotype. After applying inclusion and exclusion criteria, patients were matched and divided into SGLT2i users (n = 6572) and non-users (n = 6382). The primary endpoint was the first DKA event in patients with no prior history of DKA. Independent risk factors for DKA were assessed using Cox regression.
Over a median follow-up of 4.4 years, 239 patients experienced DKA (143 [2.22%] SGLT2i users vs. 96 [1.54%] non-users; HR [95% confidence interval, CI] 1.39 [1.07-1.79]; p = 0.014). The adjusted model confirmed an increased DKA risk with SGLT2i use (adjusted hazard ratio, aHR [95% CI] 1.50 [1.15-1.95]; p = 0.003). Baseline HbA1c >9% was associated with a 53% higher risk (aHR [95% CI] 1.53 [1.18-1.99]; p = 0.0016), while body mass index (BMI) ≤25 kg/m was linked to a 61% increased risk (aHR [95% CI] 1.61 [1.24-2.09]; p = 0.0003). Insulin use further heightened risk (aHR [95% CI] 2.35 [1.71-3.23]; p < 0.0001).
SGLT2i use in patients with an insulin-deficient phenotype is associated with increased DKA risk, particularly in those with HbA1c >9% and BMI ≤25 kg/m. Clinicians should exercise caution in these patients, carefully assessing risks and implementing mitigation strategies to ensure safe use.
确定开始使用钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）治疗的胰岛素缺乏型患者发生糖尿病酮症酸中毒（DKA）的预测因素。
这项回顾性队列研究分析了31900例年龄在18至70岁之间、被确定为胰岛素缺乏型的糖尿病患者的数据。应用纳入和排除标准后，对患者进行匹配并分为SGLT2i使用者（n = 6572）和非使用者（n = 6382）。主要终点是既往无DKA病史患者的首次DKA事件。使用Cox回归评估DKA的独立危险因素。
在中位随访4.4年期间，239例患者发生了DKA（143例[2.22%]为SGLT2i使用者，96例[1.54%]为非使用者；风险比[95%置信区间，CI]为1.39[1.07 - 1.79]；p = 0.014）。校正模型证实使用SGLT2i会增加DKA风险（校正风险比，aHR[95%CI]为1.50[1.15 - 1.95]；p = 0.003）。基线糖化血红蛋白（HbA1c）>9%与风险高53%相关（aHR[95%CI]为1.53[1.18 - 1.99]；p = 0.0016），而体重指数（BMI）≤25kg/m²与风险增加61%相关（aHR[95%CI]为1.61[1.24 - 2.09]；p = 0.0003）。使用胰岛素会进一步增加风险（aHR[95%CI]为2.35[1.71 - 3.23]；p < 0.0001）。
在胰岛素缺乏型患者中使用SGLT2i与DKA风险增加相关，尤其是在HbA1c>9%且BMI≤25kg/m²的患者中。临床医生应对这些患者谨慎行事，仔细评估风险并实施缓解策略以确保安全使用。
