AIMS/HYPOTHESIS We aimed to investigate the nationwide trends in incidence and associated risk factors, with focus on blood glucose-lowering medication, for the first hypoglycaemic episode leading to hospitalisation in Denmark among people with type 1 and 2 diabetes mellitus. METHODS A cohort study of all people with diabetes from 1977 to 2018 experiencing hypoglycaemic episodes leading to hospitalisation in 1998-2018 was established. Data were extracted from the Danish National Patient Registry. Trends in incidence rates were investigated with Poisson regression models and linear regressions, and risk factors were investigated with Cox proportional hazards models. RESULTS A total of 66,438 hypoglycaemic episodes leading to hospitalisation in 1998-2018 was investigated among 641,402 people with type 1 (mean ± SD age 37 ± 22 years) and type 2 diabetes (mean ± SD age 61 ± 17 years). Between 2003 and 2018, the incidence rate fell by 66% for type 1 diabetes (incidence rate ratio [IRR] 0.34 [95% CI 0.31, 0.36], p < 0.0001) and 61% for type 2 diabetes (IRR 0.39 [95% CI 0.36, 0.42], p < 0.0001). With respect to hypoglycaemic episodes, insulin glargine (HR 1.20 [95% CI 1.05, 1.36], p = 0.0059), insulin detemir (HR 1.18 [95% CI 1.04, 1.32], p = 0.0077) and insulin degludec (HR 1.04 [95% CI 0.81,1.33], p = 0.7706) seemed safer than human insulin (long-acting insulin HR 1.38 [95% CI 1.25, 1.52], p < 0.0001; combination insulins HR 1.84 [95% CI 1.65, 2.05], p < 0.0001) and, especially, sodium-glucose cotransporter 2 inhibitors (HR 0.43 [95% CI 0.33, 0.56], p < 0.0001), glucagon-like peptide 1 receptor agonists (HR 0.51 [95% CI 0.44, 0.58], p < 0.0001) and dipeptidyl peptidase 4 inhibitors (HR 0.44 [95% CI 0.38, 0.49], p < 0.0001) seemed safer than sulfonylureas (HR 2.27 [95% CI 2.18, 2.37], p < 0.0001). CONCLUSIONS/INTERPRETATION Incidence rates of hypoglycaemic episodes leading to hospitalisation are declining in Denmark, and the advent of new treatment alternatives may play a significant role in this decline. From a safety perspective, these findings are important and should be considered by clinicians when assessing treatment options for patients.

中文翻译：

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1998-2018 年丹麦导致住院的低血糖事件的流行病学。

目的/假设 我们旨在调查丹麦 1 型和 2 型糖尿病患者首次导致住院的低血糖事件的发病率和相关危险因素的全国趋势，重点是降血糖药物。方法 对 1977 年至 2018 年所有在 1998 年至 2018 年期间因低血糖发作导致住院的糖尿病患者进行队列研究。数据来自丹麦国家患者登记处。使用泊松回归模型和线性回归研究发病率趋势，并使用 Cox 比例风险模型研究危险因素。结果 1998-2018 年共调查了 66,438 例导致住院的低血糖事件，其中 641 例，402 人患有 1 型（平均 ± SD 年龄 37 ± 22 岁）和 2 型糖尿病（平均 ± SD 年龄 61 ± 17 岁）。2003 年至 2018 年间，1 型糖尿病的发病率下降了 66%（发病率比 [IRR] 0.34 [95% CI 0.31, 0.36]，p < 0.0001），2 型糖尿病的发病率下降了 61%（IRR 0.39 [95% CI 0.36, 0.42], p < 0.0001)。关于低血糖发作，甘精胰岛素 (HR 1.20 [95% CI 1.05, 1.36], p = 0.0059)、地特胰岛素 (HR 1.18 [95% CI 1.04, 1.32], p = 0.0077) 和德谷胰岛素 (HR 1.04 [ 95% CI 0.81,1.33], p = 0.7706) 似乎比人胰岛素更安全（长效胰岛素 HR 1.38 [95% CI 1.25, 1.52], p < 0.0001；联合胰岛素 HR 1.84 [95% CI 1.65, 2.05]， p < 0.0001)，尤其是钠-葡萄糖协同转运蛋白 2 抑制剂 (HR 0.43 [95% CI 0.33, 0.56], p < 0.0001)，胰高血糖素样肽 1 受体激动剂 (HR 0. 51 [95% CI 0.44, 0.58], p < 0.0001) 和二肽基肽酶 4 抑制剂 (HR 0.44 [95% CI 0.38, 0.49], p < 0.0001) 似乎比磺脲类药物 (HR 2.27 [95% CI 2.18, 2.37] , p < 0.0001)。结论/解释 在丹麦，导致住院的低血糖事件的发生率正在下降，新的治疗替代方案的出现可能在这种下降中发挥重要作用。从安全性的角度来看，这些发现很重要，临床医生在评估患者的治疗方案时应予以考虑。结论/解释 在丹麦，导致住院的低血糖事件的发生率正在下降，新的治疗替代方案的出现可能在这种下降中发挥重要作用。从安全性的角度来看，这些发现很重要，临床医生在评估患者的治疗方案时应予以考虑。结论/解释 在丹麦，导致住院的低血糖事件的发生率正在下降，新的治疗替代方案的出现可能在这种下降中发挥重要作用。从安全性的角度来看，这些发现很重要，临床医生在评估患者的治疗方案时应予以考虑。