OBJECTIVE To estimate real-world off-label use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 1 diabetes, estimate rates of diabetic ketoacidosis (DKA), and compare them with DKA rates observed in sotagliflozin clinical trials. RESEARCH DESIGN AND METHODS We identified initiators of SGLT2 inhibitors in the Sentinel System from March 2013 to June 2018, determined the prevalence of type 1 diabetes using a narrow and a broad definition, and measured rates of DKA using administrative claims data. Standardized incidence ratios (SIRs) were calculated using age- and sex-specific follow-up time in Sentinel and age- and sex-specific DKA rates from sotagliflozin trials 309, 310, and 312. RESULTS Among 475,527 initiators of SGLT2 inhibitors, 0.50% and 0.92% met narrow and broad criteria for type 1 diabetes, respectively. Rates of DKA in the narrow and broad groups were 7.3/100 person-years and 4.5/100 person-years, respectively. Among patients who met narrow criteria for type 1 diabetes, rates of DKA were highest for patients aged 25-44 years, especially females aged 25-44 years (19.7/100 person-years). More DKA events were observed during off-label use of SGLT2 inhibitors in Sentinel than would be expected based on sotagliflozin clinical trials (SIR = 1.83; 95% CI 1.45-2.28). CONCLUSIONS Real-world off-label use of SGLT2 inhibitors among patients with type 1 diabetes accounted for a small proportion of overall SGLT2 inhibitor use. However, the risk for DKA during off-label use was notable, especially among young, female patients. Although real-word rates of DKA exceeded the expectation based on clinical trials, results should be interpreted with caution due to differences in study methods, patient samples, and study drugs.

中文翻译：

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钠葡萄糖共转运蛋白2抑制剂在1型糖尿病和糖尿病酮症酸中毒发生率中的应用。

目的为了评估在1型糖尿病患者中现实世界中非标签使用钠-葡萄糖共转运蛋白2（SGLT2）抑制剂的情况，估计糖尿病性酮症酸中毒（DKA）的发生率，并将其与sotagliflozin临床试验中观察到的DKA发生率进行比较。研究设计与方法我们确定了Sentinel系统中从2013年3月至2018年6月使用SGLT2抑制剂的引发剂，使用狭义和广义定义确定了1型糖尿病的患病率，并使用了行政声明数据来测量DKA的发生率。使用Sentinel中特定于年龄和性别的随访时间以及来自sotagliflozin试验309、310和312的特定年龄和性别的DKA率来计算标准化的发病率（SIR）。结果在475,527名SGLT2抑制剂的引发者中，有0.50％和0.92％的人分别符合1型糖尿病的狭窄和广泛标准。狭窄和广泛组的DKA发生率分别为7.3 / 100人年和4.5 / 100人年。在满足狭窄的1型糖尿病标准的患者中，年龄25-44岁的患者，尤其是25-44岁的女性（19.7 / 100人年）的DKA发生率最高。在Sentinel的标签外使用SGLT2抑制剂期间，观察到的DKA事件多于索格列净临床试验的预期（SIR = 1.83; 95％CI 1.45-2.28）。结论SGLT2抑制剂在现实世界中的非标记使用在1型糖尿病患者中占SGLT2抑制剂使用总量的一小部分。但是，在标签外使用期间出现DKA的风险显着，尤其是在年轻的女性患者中。尽管DKA的实际单词率超出了基于临床试验的预期，