Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
Acumen LLC, Burlingame, California.
JAMA Intern Med. 2021 May 1;181(5):598-607. doi: 10.1001/jamainternmed.2020.9176.
Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use.
To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019.
Insulin glargine, insulin detemir, and NPH insulin.
The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age.
Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use.
In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.
先前的研究发现，在 2 型糖尿病患者中，长效胰岛素类似物与中性鱼精蛋白锌（NPH）胰岛素的严重低血糖风险并无差异。然而，这些研究没有关注 65 岁及以上的患者，他们的低血糖风险增加，或者没有包括同时使用餐时胰岛素的患者。
在真实环境中，检查年龄在 65 岁及以上的社区居住的 2 型糖尿病患者开始使用长效胰岛素或 NPH 胰岛素后，因低血糖而急诊就诊或住院的风险。
设计、设置和参与者：这项回顾性、新用户队列研究评估了 2007 年 1 月 1 日至 2019 年 7 月 31 日期间，医疗保险受益人中年龄在 65 岁及以上的开始使用甘精胰岛素（n=407018）、地特胰岛素（n=141588）或 NPH 胰岛素（n=26402）的患者。
甘精胰岛素、地特胰岛素和 NPH 胰岛素。
主要结局是首次因低血糖而急诊就诊或住院的时间，使用改良的验证算法定义。使用倾向评分加权 Cox 比例风险回归估计危险比（HR）和 95%置信区间。使用 Andersen-Gill 模型估计低血糖复发事件的风险。进行了事后分析，以研究年龄的可能的效应修饰。
在开始使用胰岛素的 575008 名患者中（平均[SD]年龄 74.9[6.7]岁；53%为女性），407018 名患者使用甘精胰岛素，141588 名患者使用地特胰岛素，26402 名患者使用 NPH 胰岛素。研究包括 7347 例因低血糖而急诊就诊或住院的事件（5194 例因甘精胰岛素、1693 例因地特胰岛素、460 例因 NPH 胰岛素，3 个队列的中位随访时间为 0.37 年（四分位间距，0.20-0.76 年）。与 NPH 胰岛素相比，使用甘精胰岛素和地特胰岛素与低血糖风险降低相关（甘精胰岛素与 NPH 胰岛素相比，HR 0.71；95%CI，0.63-0.80；地特胰岛素与 NPH 胰岛素相比，HR 0.72；95%CI，0.63-0.82）。在复发性事件分析中，HRs 相似。长效胰岛素类似物的保护关联因年龄而异，与同时使用餐时胰岛素无关。
在这项队列研究中，与 NPH 胰岛素相比，在 Medicare 中年龄较大的 2 型糖尿病患者中，使用长效类似物与急诊就诊或因低血糖住院的风险降低相关。然而，与同时使用餐时胰岛素无关。
