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The degree of fetal metformin exposure does not influence fetal outcome in gestational diabetes mellitus

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Abstract

The purpose of the study was to examine in vivo placental transfer of metformin, its association with neonatal outcome in metformin-treated gestational diabetes (GDM) patients, and influence of metformin exposure on maternal glycemic control and weight gain. Two hundred and seventeen GDM patients were randomized to metformin or insulin in Turku University Hospital, Finland. Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks (gw) and at birth, and in umbilical cord blood. Main outcome measures were birth weight, gw at birth, umbilical artery pH and neonatal hypoglycemia, maternal weight gain, HbA1c and fructosamine concentration. Median umbilical cord/maternal serum metformin concentration ratio was 0.73. There were no differences in birth weight measured in grams or SD units (p = 0.49), or gw at birth (p always ≥0.49) between insulin- and metformin-treated patients stratified by trough metformin concentration tertiles measured at 36 gw. Rate of neonatal hypoglycemia (p = 0.92) and umbilical artery pH value (p = 0.78) was similar in insulin- and metformin-treated patients stratified by cord metformin concentration tertiles. Maternal glycemic control was similar in metformin concentration tertiles at 36 gw. Maternal weight gain was 223 g greater per week (p = 0.038) in the lowest metformin tertile compared to other tertiles combined. Maternal and fetal exposure to metformin is similar. Maternal or fetal metformin concentrations do not predict maternal glycemic control or neonatal outcome, but low maternal exposure may lead to greater maternal weight gain.

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Acknowledgments

We thank Tero Vahlberg for his assistance in statistical analyses. We thank all midwives of the Department of Obstetrics and Gynecology in Turku University Hospital, who contributed to the study. We also thank all the women who agreed to take part in the study. The study was financially supported by the Clinical Research (EVO) funding of Turku University Hospital and the National Graduate School of Clinical Investigation (CLIGS).

Conflict of interest

Kristiina Tertti, Kari Laine, Ulla Ekblad, Valtteri Rinne and Tapani Rönnemaa declare they have no conflict of interest.

Statement of Human and Animal Rights

All procedures followed were in accordance with the Ethics Committee of Southwest Hospital District, the Finnish National Agency of Medicines, and the European Union Drug Regulatory Agency (EUDRA) and with the Helsinki Declaration of 1975, as revised in 2008 (5). The trial was registered in Clinicaltrials.gov, NCT01240785; http://clinicaltrials.gov/ct2/show/NCT01240785.

Statement of Informed Consent

Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland

    Kristiina Tertti & Ulla Ekblad

  2. Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

    Kari Laine & Valtteri Rinne

  3. Medbase Ltd, Turku, Finland

    Kari Laine

  4. Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland

    Tapani Rönnemaa

  5. Department of Obstetrics and Gynecology, Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland

    Kristiina Tertti

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  1. Kristiina Tertti
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  2. Kari Laine
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  3. Ulla Ekblad
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  4. Valtteri Rinne
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  5. Tapani Rönnemaa
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Correspondence to Kristiina Tertti.

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Tertti, K., Laine, K., Ekblad, U. et al. The degree of fetal metformin exposure does not influence fetal outcome in gestational diabetes mellitus. Acta Diabetol 51, 731–738 (2014). https://doi.org/10.1007/s00592-014-0570-6

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  • DOI: https://doi.org/10.1007/s00592-014-0570-6

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