Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes
Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes
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DOI：
10.1001/jama.2018.7993
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发表时间：
2018-07-03
影响因子：
120.7
通讯作者：
Karter, Andrew J.
中科院分区：
文献类型：
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作者：
Lipska, Kasia J.;Parker, Melissa M.;Karter, Andrew J.
重要性在2型糖尿病患者的临床试验中，长效胰岛素类似物与人中性鱼精蛋白哈格多恩（NPH）胰岛素相比，可适度降低夜间低血糖的风险，但成本要高出2至10倍。临床实践中的结果可能与试验结果不同。目的比较2型糖尿病患者中与长效胰岛素类似物和人NPH胰岛素相关的低血糖相关急诊（艾德）就诊或住院率。设计、设置和参与者一项回顾性观察性研究，使用来自北方加州Kaiser Permanente的数据，至2015年9月30日。纳入开始使用长效胰岛素类似物或NPH胰岛素的2型糖尿病患者，并在死亡、失去健康计划覆盖、胰岛素治疗改变或9月30日研究结束时进行删失，2015.EXPOSURE开始使用基础胰岛素类似物（甘精胰岛素或地特胰岛素）vs NPH胰岛素。主要结果和测量主要结果是低血糖的时间-结果：25489例2型糖尿病患者开始基础胰岛素治疗后1年内血红蛋白A（1c）水平的变化（平均年龄，60.2 [SD，11.8]岁; 51.9%白色; 46.8%女性）。在平均1.7年的随访中，在1928例开始使用胰岛素类似物的患者中，有39例低血糖相关的艾德就诊或住院（11.9起事件[95% CI，8.1 - 15.6]/1000人-年），与23561例开始使用NPH胰岛素的患者中354例低血糖相关艾德访视或住院相比（8.8起事件[95% CI，7.9 - 9.8]/1000人-年）（组间差异，3.1起事件[95% CI，-1.5 - 7.7]/1000人-年; P = 0.07）。在4428例按倾向评分匹配的患者中，低血糖相关艾德访视或与胰岛素类似物使用相关的住院治疗的校正风险比为1.16（95% CI，0.71 - 1.78）。在开始胰岛素治疗的1年内，血红蛋白A1 c水平从9.4%下降到2.4%，（95% CI，9.3%至9.5%）至8.2%（95% CI，8.1%-8.2%），从9.4%（95% CI，9.3%至9.5%）至7.9%开始NPH胰岛素治疗后（95% CI，7.9%-8.0%）（血糖控制的校正差异中的差异，-0.22%[95%CI，-0.09%至-0.37%]）。与NPH胰岛素相比，开始使用基础胰岛素类似物与低血糖相关艾德就诊或住院的风险降低或血糖控制改善无关。这些结果表明，在常规实践环境中使用基础胰岛素类似物可能与这些结局的临床优势无关。
IMPORTANCE In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from trial results.OBJECTIVE To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes.DESIGN, SETTING, AND PARTICIPANTS A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss of health plan coverage, change in insulin treatment, or study end on September 30, 2015.EXPOSURE Initiation of basal insulin analogs (glargine or detemir) vs NPH insulin.MAIN OUTCOMES AND MEASURES The primary outcome was the time to a hypoglycemia-related ED visit or hospital admission and the secondary outcome was the change in hemoglobin A(1c) level within 1 year of insulin initiation.RESULTS There were 25 489 patients with type 2 diabetes who initiated basal insulin therapy (mean age, 60.2 [SD, 11.8] years; 51.9% white; 46.8% female). During a mean follow-up of 1.7 years, there were 39 hypoglycemia-related ED visits or hospital admissions among 1928 patients who initiated insulin analogs (11.9 events [95% CI, 8.1 to 15.6] per 1000 person-years) compared with 354 hypoglycemia-related ED visits or hospital admissions among 23 561 patients who initiated NPH insulin (8.8 events [95% CI, 7.9 to 9.8] per 1000 person-years) (between-group difference, 3.1 events [95% CI,-1.5 to 7.7] per 1000 person-years; P =.07). Among 4428 patients matched by propensity score, the adjusted hazard ratio was 1.16 (95% CI, 0.71 to 1.78) for hypoglycemia-related ED visits or hospital admissions associated with insulin analog use. Within 1 year of insulin initiation, hemoglobin A1c level decreased from 9.4%(95% CI, 9.3% to 9.5%) to 8.2%(95% CI, 8.1% to 8.2%) after initiation of insulin analogs and from 9.4%(95% CI, 9.3% to 9.5%) to 7.9%(95% CI, 7.9% to 8.0%) after initiation of NPH insulin (adjusted difference-in-differences for glycemic control,-0.22%[95% CI,-0.09% to-0.37%]).CONCLUSIONS AND RELEVANCE Among patients with type 2 diabetes, initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.