Metformin serum concentrations during pregnancy and post partum – A clinical study in patients with polycystic ovary syndrome

Background and objectives Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of m...

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Published in:	Basic & clinical pharmacology & toxicology Vol. 130; no. 3; pp. 415 - 422
Main Authors:	Espnes, Ketil Arne, Hønnås, Arne, Løvvik, Tone S., Gundersen, Per Ole M., Naavik, Audhild, Skogvoll, Eirik, Westin, Andreas A., Spigset, Olav, Vanky, Eszter
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-03-2022 John Wiley and Sons Inc
Subjects:	Diabetes mellitus Metformin Original Ovaries Pharmacokinetics Polycystic ovary syndrome post partum Pregnancy Premature birth Side effects Subgroups pharmacokinetics metformin post partum pregnancy polycystic ovary syndrome
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Summary:	Background and objectives Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy‐related changes in metformin pharmacokinetics and the return to the non‐pregnant state. Method A subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time‐points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four‐parameter logistic model. Findings The mean steady‐state serum concentration of metformin during pregnancy was 9.39 μmoL/L, whereas the post partum concentration was 12.36 μmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum. Conclusion Clinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.
Bibliography:	Funding information The Clinic of Laboratory Medicine, St. Olav's Hospital Funding information The Clinic of Laboratory Medicine, St. Olav's Hospital Correction added on 7 February 2022, after first online publication: ORCID ID has been added for authors Arne Hønnås, Tone S. Løvvik, Audhild Naavik, Eirik Skogvoll, Andreas A. Westin, Olav Spigset, and Eszter Vanky.
ISSN:	1742-7835 1742-7843
DOI:	10.1111/bcpt.13703