Non-adherence to cardiometabolic medication as assessed by LC-MS/MS in urine and its association with kidney and cardiovascular outcomes in type 2 diabetes mellitus

Sara Denicolò; Vera Reinstadler; Felix Keller; Stefanie Thöni; Susanne Eder; Hiddo J L Heerspink; László Rosivall; Andrzej Wiecek; Patrick B Mark; Paul Perco; Johannes Leierer; Andreas Kronbichler; Herbert Oberacher; Gert Mayer

doi:10.1007/s00125-024-06149-w

Non-adherence to cardiometabolic medication as assessed by LC-MS/MS in urine and its association with kidney and cardiovascular outcomes in type 2 diabetes mellitus

Diabetologia. 2024 Apr 22. doi: 10.1007/s00125-024-06149-w. Online ahead of print.

Affiliations

¹ Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria. sara.denicolo@i-med.ac.at.
² Institute of Legal Medicine and Core Facility Metabolomics, Medical University Innsbruck, Innsbruck, Austria.
³ Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.
⁴ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ International Nephrology Research and Training Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.
⁶ Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland.
⁷ School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.

PMID: 38647650
DOI: 10.1007/s00125-024-06149-w

Abstract

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.

Keywords: Adherence; Cardiovascular disease; Diabetic kidney disease; Type 2 diabetes mellitus.

Non-adherence to cardiometabolic medication as assessed by LC-MS/MS in urine and its association with kidney and cardiovascular outcomes in type 2 diabetes mellitus

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Abstract

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