Syafhan Nadia Farhanah, Donnelly Rosemary, Harper Roy, Harding Janet, Mulligan Ciara, Hogg Anita, Scott Michael, Fleming Glenda, Scullin Claire, Hawwa Ahmed F, Chen Gaoyun, Parsons Carole, McElnay James C
Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, Belfast, UK.
Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
J Pharm Policy Pract. 2022 Oct 12;15(1):61. doi: 10.1186/s40545-022-00457-5.
Medication adherence, one of the most important aspects in the process of optimal medicines use, is unfortunately still a major challenge in modern healthcare, and further research is required into how adherence can be assessed and optimised. The aim of this study was to use a combined method approach of self-report and dried blood spot (DBS) sampling coupled with population pharmacokinetic (PopPK) modelling, to assess adherence to metformin in adult patients with type 2 diabetes. Further aims were to assess metformin exposure levels in patients, determine factors associated with non-adherence with prescribed metformin, and to explore the relationship between adherence and therapeutic outcomes.
A combined method approach was used to evaluate metformin adherence in patients with type 2 diabetes who had been prescribed metformin for a minimum period of 6 months. Patients were recruited from consultant-led diabetic outpatient clinics at three hospitals in Northern Ireland, UK. Data collection involved self-reported questionnaires [Medication Adherence Report Scale (MARS), Beliefs about Medicines Questionnaire and Centre for Epidemiologic Studies Depression Scale], direct measurement of metformin concentration in DBS samples, and researcher-led patient interviews. The DBS sampling approach was coupled with population pharmacokinetic (PopPK) modelling, which took account of patient characteristics, metformin dosage and type of formulation prescribed (immediate or sustained release).
The proportion of patients considered to be adherent to their prescribed metformin, derived from self-reported MARS scores and metformin concentration in DBS samples, was 61.2% (74 out of 121 patients). The majority (n = 103, 85.1%) of recruited patients had metformin exposure levels that fell within the therapeutic range. However, 17 patients (14.1%) had low exposure to metformin and one patient (0.8%) had undetectable metformin level in their blood sample (non-exposure). Metformin self-administration and use of a purchased adherence pill box significantly increased the probability of a patient being classified as adherent based on logistic regression analysis. Both HbA1c and random glucose levels (representing poor glycaemic control) in the present research were, however, not statistically linked to non-adherence to metformin (P > 0.05).
A significant proportion of participating patients were not fully adherent with their therapy. DBS sampling together with the use of a published PopPK model was a useful, novel, direct, objective approach to estimate levels of adherence in adult patients with type 2 diabetes (61.2%).
药物依从性是优化药物使用过程中最重要的方面之一，但遗憾的是，它仍是现代医疗保健中的一项重大挑战，仍需进一步研究如何评估和优化依从性。本研究的目的是采用自我报告和干血斑（DBS）采样相结合的方法，并结合群体药代动力学（PopPK）建模，来评估2型糖尿病成年患者对二甲双胍的依从性。进一步的目的是评估患者的二甲双胍暴露水平，确定与未按规定服用二甲双胍相关的因素，并探讨依从性与治疗效果之间的关系。
采用一种联合方法来评估已服用二甲双胍至少6个月的2型糖尿病患者的二甲双胍依从性。患者从英国北爱尔兰三家医院由顾问主导的糖尿病门诊招募。数据收集包括自我报告问卷[药物依从性报告量表（MARS）、药物信念问卷和流行病学研究中心抑郁量表]、直接测量DBS样本中的二甲双胍浓度，以及由研究人员主导的患者访谈。DBS采样方法与群体药代动力学（PopPK）建模相结合，该建模考虑了患者特征、二甲双胍剂量和所开处方制剂的类型（速释或缓释）。
根据自我报告的MARS评分和DBS样本中的二甲双胍浓度，被认为依从规定二甲双胍治疗的患者比例为61.2%（121名患者中的74名）。大多数（n = 103，85.1%）招募的患者的二甲双胍暴露水平在治疗范围内。然而，17名患者（14.1%）的二甲双胍暴露水平较低，1名患者（0.8%）的血液样本中二甲双胍水平无法检测到（无暴露）。根据逻辑回归分析，二甲双胍的自我给药和使用购买来的依从性药盒显著增加了患者被归类为依从的可能性。然而，本研究中的糖化血红蛋白（HbA1c）和随机血糖水平（代表血糖控制不佳）在统计学上均与未依从二甲双胍治疗无关（P > 0.05）。
相当一部分参与研究的患者未完全依从治疗。DBS采样与已发表的PopPK模型的使用相结合，是一种有用、新颖、直接、客观的方法，可用于估计2型糖尿病成年患者的依从水平（61.2%）。
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