TOPLINE:

Women who took metformin for at least 6 months before conception had lower odds of developing hyperemesis gravidarum (HG) during pregnancy; the benefit was similar for those who continued metformin in the 2 months before conception or during the first month of pregnancy.

METHODOLOGY:

• Researchers conducted a population‑based cohort study using Danish registries to determine whether using metformin before conception, and for how long, can lower the frequency of HG during pregnancy.
• They included 1,448,968 singleton pregnancies with a registered birth outcome and gestational age at the end of pregnancy (at least 10 weeks), of whom 11,860 participants filled at least one prescription for metformin before conception.
• Metformin exposure was identified using filled prescriptions up to 2 years before conception. The duration of use and the time from the last prescription fill to conception were estimated from prescription records.

TAKEAWAY:

• Overall, the use of metformin before conception reduced neither the prevalence of HG (1.9% vs 1.9%) nor the recurrence of HG (26% vs 27%) in metformin users vs non-users.
• Participants who used metformin for at least 6 months had 51% lower odds of HG than those who used it for less than 2 months (adjusted odds ratio, 0.49; 95% CI, 0.31-0.75).
• Those who continued metformin into the first month of pregnancy had 39% lower odds of HG than those who discontinued it for more than 6 months before conception.
• The short-term use of metformin before conception was not associated with a significant reduction in the risk for HG during pregnancy.

IN PRACTICE:

"[The study] findings may help inform future trials on the optimal duration and timing of metformin treatment, suggesting that longer use (> 6 months) and continuation up to or into conception may be most beneficial," the authors wrote.

SOURCE:

This study was led by Loïs M. van der Minnen, Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, Netherlands. It was published online on December 30, 2025, in the American Journal of Obstetrics and Gynecology.

LIMITATIONS:

A large proportion of patients received metformin prescriptions without registered indications. This study relied on hospital-based International Classification of Diseases codes for the diagnosis of HG, which may have led to misclassification and underreporting of milder or recurrent cases managed in primary care. The inclusion of a small number of participants with prior HG who received metformin may have limited the statistical power to detect significant associations in this subgroup.

DISCLOSURES:

This study did not receive any funding. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.