Sex-specific effects of maternal metformin intervention during glucose-intolerant obese pregnancy on body composition and metabolic health in aged mouse offspring – published online 16/09/2022

Josca M. Schoonejans, Heather L. Blackmore, Thomas J. Ashmore, Lucas C. Pantaleão, Luciana Pellegrini Pisani, Laura Dearden, John A. Tadross, Catherine E. Aiken, Denise S. Fernandez-Twinn, Susan E. Ozanne

Metformin is used to treat gestational diabetes in many countries. Although beneficial for the mother and safe for the neonate, the long-term effects on exposed offspring remain unknown. In this issue, Schoonejans et al (https://doi.org/10.1007/s00125-022-05789-0) report that maternal metformin treatment in a mouse model of obese glucose-intolerant pregnancy leads to sex- and age-specific increases in metabolic risk factors in exposed offspring. The authors propose that fetal metformin exposure can adversely influence adipose tissue development, leading to a postnatal phenotype characterised by adiposity, adipose tissue inflammation and ectopic lipid deposition in tissues such as the liver. The authors conclude that the findings highlight the complexity of balancing short-term beneficial maternal or fetal effects and long-term offspring consequences of placenta-crossing therapies such as metformin, and stress the importance of following up offspring of both sexes throughout life.

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