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Time course, outcome and management of adverse drug reactions associated with metformin from patient’s perspective: a prospective, observational cohort study in the Netherlands

  • Pharmacoepidemiology and Prescription
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The aim of this study was to gather information about frequency, latency time, outcome and management of frequently occurring adverse drug reactions (ADRs) related to the use of metformin in daily practice.


A prospective, observational cohort study was performed. A total of 2490 first-time metformin users were recruited through pharmacies in the Netherlands between February 1, 2008, and April 1, 2012. Patients were invited to complete six web-based questionnaires at 2-week, 6-week, 3-month, 6-month, 9-month and 12-month intervals after starting treatment with metformin. Information was gathered about patient characteristics, ADRs and drug use.


The occurrence of at least one possible ADR related to the use of metformin was reported by 34.5 % of the patients. A higher proportion of females reported the occurrence of an ADR (39.6 %) compared to the proportion in males (30.9 %). Some patients (11.4 %) stopped using metformin within 1 year after start. More than half of the patients (50.8 %) undertook no action regarding metformin after the occurrence of ADRs. A high number of patients (77.7 %) recovered or were still recovering from ADRs despite continuation of metformin. Most ADRs occurred shortly after the beginning of the treatment, with a median latency time of 1–6 days. The study revealed some ADR-specific differences in occurrence rate, latency time, management and outcome.


This study successfully obtained information about frequency, latency time, outcome and management of frequently occurring ADRs related to the use of metformin in daily practise.

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The support of pharmacies in the Netherlands is very much appreciated. We want to thank all the patients who participated in this study, without whom this study would have not been possible.

Contributions of authors

LH and EP are responsible for the study conception and planning. LJ and EP are responsible for the acquisition, analysis or interpretation of data. LJ is responsible for the drafting of the manuscript. LH and EP are responsible for the critical revision of the manuscript.

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Correspondence to Loek de Jong.

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The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standard. Privacy policy agreement was obtained from all individual participants included in the study

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de Jong, L., Härmark, L. & van Puijenbroek, E. Time course, outcome and management of adverse drug reactions associated with metformin from patient’s perspective: a prospective, observational cohort study in the Netherlands. Eur J Clin Pharmacol 72, 615–622 (2016).

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