Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
Similar content being viewed by others
References
Dutch Summary of Product Characteristics of metformin generic brands. http://www.cbg-meb.nl/CBG/nl/humane-geneesmiddelen/geneesmiddeleninformatiebank/default.htm. Accessed November 21, 2014.
Kajbaf F, Lalau JD (2014) Mortality rate in so-called “metformin-associated lactic acidosis”: a review of the data since the 1960s. Pharmacoepidemiol Drug Saf 23(11):1123–1127
Grandy S, Fox KM, Hardy E (2013) Association of weight loss and medication adherence among adults with type 2 diabetes mellitus: SHIELD (Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes). Curr Ther Res Clin Exp 75:77–82
Maningat P, Gordon BR, Breslow JL (2013) How do we improve patient compliance and adherence to long-term statin therapy? Curr Atheroscler Rep 15(1):291
Clifford S, Barber N, Horne R (2008) Understanding different beliefs held by adherers, unintentional nonadherers, and intentional nonadherers: application of the necessity-concerns framework. J Psychosom Res 64(1):41–46
de Vries ST, Keers JC, Visser R, de Zeeuw D, Haaijer-Ruskamp FM, Voorham J, Denig P (2014) Medication beliefs, treatment complexity, and non-adherence to different drug classes in patients with type 2 diabetes. J Psychosom Res 76(2):134–138
Sweileh WM, Zyoud SH, Abu Nab’a RJ, Deleq MI, Enaia MI, Nassar SM, Al-Jabi SW (2014) Influence of patients’ disease knowledge and beliefs about medicines on medication adherence: findings from a cross-sectional survey among patients with type 2 diabetes mellitus in Palestine. BMC Public Health 14:94
Mann DM, Ponieman D, Leventhal H, Halm EA (2009) Predictors of adherence to diabetes medications: the role of disease and medication beliefs. J Behav Med 32(3):278–284
Harmark L, van Puijenbroek E, van Grootheest K (2013) Intensive monitoring of duloxetine: results of a web-based intensive monitoring study. Eur J Clin Pharmacol 69(2):209–215
CIOMS Working Group IV. Benefit-risk balance for marketed drugs: evaluating safety signals. Geneva: CIOMS.http://www.cioms.ch/publications/g4-benefit-risk.pdf. Accessed March 9, 2015.
MedDRA. http://www.meddra.org/. Accessed August 5, 2014.
Z-Index. http://www.z-index.nl/english. Accessed August 5, 2014.
Stichting Farmaceutische Kengetallen. http://www.sfk.nl/over-de-sfk. Accessed December 11, 2014.
Hofer-Dueckelmann C, Prinz E, Beindl W, Szymanski J, Fellhofer G, Pichler M, Schuler J (2011) Adverse drug reactions (ADRs) associated with hospital admissions—elderly female patients are at highest risk. Int.J Clin.Pharmacol.Ther 49(10):577–586
Fattinger K, Roos M, Vergeres P, Holenstein C, Kind B, Masche U, Stocker DN, Braunschweig S, Kullak-Ublick GA, Galeazzi RL, et al. (2000) Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine. Br J Clin Pharmacol 49(2):158–167
Martin RM, Biswas PN, Freemantle SN, Pearce GL, Mann RD (1998) Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br.J Clin. Pharmacology 46(5):505–511
Zopf Y, Rabe C, Neubert A, Gassmann KG, Rascher W, Hahn EG, Brune K, Dormann H (2008) Women encounter ADRs more often than do men. Eur J Clin Pharmacol 64(10):999–1004
Montastruc JL, Lapeyre-Mestre M, Bagheri H, Fooladi A (2002) Gender differences in adverse drug reactions: analysis of spontaneous reports to a Regional Pharmacovigilance Centre in France. Fundam Clin Pharmacol 16(5):343–346
Oosterhuis I, Harmark L, van Puijenbroek E (2014) Experiences with the use of varenicline in daily practice in the Netherlands: a prospective, observational cohort study. Drug Saf 37(6):449–457
Hsia Y, Dawoud D, Sutcliffe AG, Viner RM, Kinra S, Wong IC (2012) Unlicensed use of metformin in children and adolescents in the UK. Br J Clin Pharmacol 73(1):135–139
Harmark L, Lie-Kwie M, Berm L, GH d, GK v (2013) Patients’ motives for participating in active post-marketing surveillance. Pharmacoepidemiol Drug Saf 22(1):70–76
Acknowledgments
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
No funding source.
Conflict of interest
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
Electronic supplementary materials
Online Resource 1
(DOCX 18.8 kb)
Online Resource 2
(DOCX 13.8 kb)
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1007/s00228-016-2019-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-016-2019-z