Aims/hypothesis

Non-adherence to medication is a frequent barrier in the treatment of patients with type 2 diabetes mellitus, potentially limiting the effectiveness of evidence-based treatments. Previous studies have mostly relied on indirect adherence measures to analyse outcomes based on adherence. The aim of this study was to use LC-MS/MS in urine—a non-invasive, direct and objective measure—to assess non-adherence to cardiometabolic drugs and analyse its association with kidney and cardiovascular outcomes.

Methods

This cohort study includes 1125 participants from the PROVALID study, which follows patients with type 2 diabetes mellitus at the primary care level. Baseline urine samples were tested for 79 cardiometabolic drugs and metabolites thereof via LC-MS/MS. An individual was classified as totally adherent if markers for all drugs were detected, partially non-adherent when at least one marker for one drug was detected, and totally non-adherent if no markers for any drugs were detected. Non-adherence was then analysed in the context of cardiovascular (composite of myocardial infarction, stroke and cardiovascular death) and kidney (composite of sustained 40% decline in eGFR, sustained progression of albuminuria, kidney replacement therapy and death from kidney failure) outcomes.

Results

Of the participants, 56.3% were totally adherent, 42.0% were partially non-adherent, and 1.7% were totally non-adherent to screened cardiometabolic drugs. Adherence was highest to antiplatelet and glucose-lowering agents and lowest to lipid-lowering agents. Over a median (IQR) follow-up time of 5.10 (4.12–6.12) years, worse cardiovascular outcomes were observed with non-adherence to antiplatelet drugs (HR 10.13 [95% CI 3.06, 33.56]) and worse kidney outcomes were observed with non-adherence to antihypertensive drugs (HR 1.98 [95% CI 1.37, 2.86]).

Conclusions/interpretation

This analysis shows that non-adherence to cardiometabolic drug regimens is common in type 2 diabetes mellitus and negatively affects kidney and cardiovascular outcomes.

Graphical Abstract

中文翻译：

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通过 LC-MS/MS 评估尿液中心脏代谢药物的不依从性及其与 2 型糖尿病患者肾脏和心血管结局的关系

目标/假设

不坚持服药是 2 型糖尿病患者治疗中常见的障碍，可能限制循证治疗的有效性。以前的研究主要依靠间接依从性措施来分析基于依从性的结果。本研究的目的是利用尿液中的 LC-MS/MS（一种非侵入性、直接且客观的测量方法）来评估心脏代谢药物的不依从性，并分析其与肾脏和心血管结局的关系。

方法

该队列研究包括来自 PROVALID 研究的 1125 名参与者，该研究跟踪初级保健水平的 2 型糖尿病患者。通过 LC-MS/MS 对基线尿液样本中的 79 种心脏代谢药物及其代谢物进行了检测。如果检测到所有药物的标记，则将个体归类为完全依从；如果检测到一种药物的至少一种标记，则将个体归类为部分不依从；如果没有检测到任何药物的标记，则将个体归类为完全不依从。然后结合心血管（心肌梗塞、中风和心血管死亡的综合）和肾脏（eGFR 持续下降 40%、白蛋白尿持续进展、肾脏替代治疗和肾衰竭死亡的综合）结果对不依从性进行分析。

结果

在参与者中，56.3% 完全依从筛选的心脏代谢药物，42.0% 部分不依从，1.7% 完全不依从。抗血小板药物和降血糖药物的依从性最高，降脂药物的依从性最低。在中位 (IQR) 随访时间 5.10 (4.12–6.12) 年中，观察到不坚持使用抗血小板药物的心血管结局更差（HR 10.13 [95% CI 3.06, 33.56]），并且观察到不坚持使用抗血小板药物的肾脏结局更差。不坚持服用抗高血压药物（HR 1.98 [95% CI 1.37, 2.86]）。

结论/解释

该分析表明，不遵守心脏代谢药物治疗方案在 2 型糖尿病中很常见，并对肾脏和心血管结局产生负面影响。

图形概要