Can Metformin Prevent Severe Morning Sickness?
Daily metformin use in the month before pregnancy is associated with more than 70% reduction in risk for hyperemesis gravidarum in first pregnancies. The protective effect persists in second pregnancies with 82% lower risk, even after accounting for the high recurrence risk, while cannabis use and selective serotonin reuptake inhibitors increase risk.
METHODOLOGY:
Researchers analyzed data from 5414 participants who reported on daily medication and substance use in the month prior to pregnancy and level of nausea and vomiting during pregnancy.
Participants were recruited through the Hyperemesis Gravidarum Education and Research Foundation social media sites from January 2023 to September 2024.
Analysis included logistic regression to estimate crude and multivariate associations between use of 32 common substances and severe nausea and vomiting of pregnancy/hyperemesis gravidarum.
Final multivariate models incorporated tobacco use and maternal age, while number and type of additional drugs used and race/ethnicity showed minimal influence.
TAKEAWAY:
Prepregnancy metformin use was associated with more than 70% reduction in risk for hyperemesis gravidarum (adjusted relative risk [aRR], 0.29; 95% CI, 0.12-0.71; P = .007).
Tobacco use showed significant reduction in risk (aRR, 0.51; 95% CI, 0.30-0.86; P = .011), while selective serotonin reuptake inhibitors were linked to increased risk (aRR, 2.41; 95% CI, 1.33-4.38; P = .004).
Metformin use before a second pregnancy was associated with 82% lower risk for severe nausea and vomiting/hyperemesis gravidarum (adjusted odds ratio [aOR], 0.18; 95% CI, 0.06-0.59; P = .005), even after adjusting for an 86% recurrence risk.
Cannabis use (aOR, 3.48; 95% CI, 1.80-6.75; P < .001) and selective serotonin reuptake inhibitors (aOR, 1.84; 95% CI, 1.12-3.04; P = .016) before a second pregnancy were associated with increased risk.
IN PRACTICE:
'Metformin, which is routinely used pre- and post-conception, may be a safe and affordable treatment to offer patients with a prior history of hyperemesis gravidarum to decrease the chance of recurrence. Clinical trials are warranted to investigate metformin use prior to pregnancy to lower hyperemesis gravidarum risk, thereby mitigating the associated adverse maternal and offspring outcomes,' wrote the authors of the study.
SOURCE:
The study was led by Neelu Sharma, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California in Los Angeles. It was published online in American Journal of Obstetrics and Gynecology.
LIMITATIONS:
The hyperemesis gravidarum-enriched approach to participant recruitment may have introduced selection bias, as individuals with multiple occurrences may have been more likely to participate. However, the authors noted that similar recurrence rates were reported in previous prospective studies. Additionally, the indication, timing, and dosage for each medication or substance was unknown. While conditions commonly treated with metformin like diabetes and polycystic ovary syndrome have been associated with increased risk for hyperemesis gravidarum, any confounding by indication would bias results upward rather than explain the observed inverse associations.
DISCLOSURES:
Marlena S. Fejzo disclosed being a consultant for NGM Biosciences, receiving stock and fee for service. The remaining coauthors reported 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.
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