Published July 29, 2023 | Version v1
Journal article Open

Metformin Versus Insulin and Risk of Major Congenital Malformations in Pregnancies With Type 2 Diabetes: A Nordic Register-Based Cohort Study

Creators

  • 1. Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Centre for Fertility and Health, Norwegian Institute of Public Health
  • 2. Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet
  • 3. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  • 4. Department of Knowledge Brokers, Finnish Institute for Health and Welfare, Helsinki, Finland
  • 5. Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
  • 6. Karolinska Institutet
  • 7. School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia

Description

OBJECTIVE

To assess the risk of major congenital malformations with metformin versus insulin in pregnancies with type 2 diabetes.

RESEARCH DESIGN AND METHODS

This cohort study used four Nordic countries’ nationwide registers of live and stillborn infants exposed to metformin or insulin during first trimester organogenesis. Main exclusion criteria were type 1 diabetes, polycystic ovary syndrome, fertility treatment, and exposure to other diabetes drugs. Adjusted risk ratios (RRs) and 95% CIs were estimated for any and cardiac malformations.

RESULTS

Of 3,734,125 infants in the source population, 25,956 were exposed to metformin or insulin in the first trimester, and 4,023 singleton infants were included. A malformation was diagnosed in 147 (4.7%) of 3,145 infants with exposure to any metformin (alone or in addition to insulin) and 50 (5.7%) of 878 infants with exposure to insulin alone (RR 0.84, 95% CI 0.46–1.54). Among 2,852 infants exposed to metformin alone and 293 infants exposed to metformin in addition to insulin 127 (4.4%) and 20 (6.8%), respectively, had a malformation. The adjusted risk was not increased for either metformin alone (0.83, 0.44–1.58) or both metformin and insulin (0.98, 0.56–1.69) versus insulin alone. Corresponding RRs for cardiac malformations were 1.01 (0.55–1.84) for any metformin, 0.92 (0.47–1.81) for metformin alone, and 1.72 (0.76–3.91) for both metformin and insulin.

CONCLUSIONS

No evidence of an increased malformation risk with metformin versus insulin in the first trimester was found. Results should be interpreted with caution since information on glycemic control was missing

Notes

This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 844728. Additionally, this study was funded by NordForsk as part of the Nordic Pregnancy Drug Safety Studies (NorPreSS) (project no. 83539), by the Research Council of Norway as part of the International Pregnancy Drug Safety Studies (InPreSS) (project no. 273366), and partly by the Research Council of Norway through its Centers of Excellence funding scheme (project no. 262700). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript.

Files

2023 Kjerpeseth Metformin Versus Insulin and Risk of Major Congenital Malformations in Pregnancies With Type 2 Diabetes.pdf

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Additional details

Funding

InPreSS – International Pregnancy Safety Study 844728
European Commission