Veterans Health Administration Tennessee Valley Healthcare System, Geriatric Research and Education Clinical Centre, HSR&D Centre, Nashville, TN, USA.
Department of Health Policy, Vanderbilt University Medical Centre, Nashville, TN, USA.
Diabet Med. 2019 Apr;36(4):482-490. doi: 10.1111/dme.13853. Epub 2018 Nov 20.
To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea.
We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180-day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines.
Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50-100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person-years were 23.1 (95% CI 21.1-25.4) and 24.5 (95% CI 22.7-26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84-1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable.
We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea.
评估最近二甲双胍单药治疗依从性低是否与加用磺酰脲类药物后发生低血糖有关。
我们组建了一个退伍军人队列，这些退伍军人在 2001 年至 2011 年间新开具了二甲双胍处方，并在使用二甲双胍≥1 年后强化使用磺酰脲类药物。我们根据强化治疗前 180 天的覆盖天数比例，从药房数据中计算二甲双胍的依从性。主要结局是低血糖，定义为强化治疗后 1 年内因低血糖住院或到急诊就诊，或门诊血糖测量值<3.3mmol/l。我们使用 Cox 比例风险模型比较低（<80%）和高（≥80%）依从性参与者发生低血糖的风险。我们还使用受限立方样条模型将依从性作为连续变量进行建模。
在 187267 名开始使用二甲双胍单药治疗的参与者中，有 49424 名在≥1 年后加用了磺酰脲类药物。治疗依从性中位数（四分位距）为 87（50-100）%，43%的参与者依从性<80%。低依从性和高依从性参与者的低血糖发生率分别为每 1000 人年 23.1（95%CI 21.1-25.4）和 24.5（95%CI 22.7-26.4）（调整后的危险比 0.95，95%CI 0.84-1.08）。当依从性作为连续变量建模时，在所有依从性水平下，低血糖的风险均相似。
我们没有发现过去二甲双胍单药治疗依从性低与加用磺酰脲类药物后发生低血糖有关的证据。
