Metformin for the Prevention of Hyperemesis Gravidarum: An Observational Cohort Study

Objective

To evaluate if metformin treatment prior to pregnancy reduces the likelihood of nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) compared to no exposure.

Design

Observational cohort study.

Setting

The MotherToBaby Pregnancy Studies in the United States and Canada.

Sample

Live-born singleton pregnancies enrolled between 2012 and 2023, with HG diagnosis data available.

Methods

Data were collected via maternal telephone interviews during pregnancy and medical records. Outcomes were compared between women with preconceptional metformin exposure and those unexposed to metformin before or during pregnancy.

Main Outcome Measures

Risk ratios (RR) and 95% confidence intervals (CI) for HG and NVP, and mean duration of NVP symptoms.

Results

Data from 80 women exposed to metformin before conception and 4411 non-exposed women were analysed. In this cohort, the frequency of women with HG was lower among the exposed than the unexposed women (n = 1/80; 1.25% vs. n = 97/4411; 2.20%), but the study was not powered to detect statistical significance (adjusted RR 0.50, 95% CI 0.07–3.39). Rates of NVP were similar between groups (n = 32/80; 88.90% in the exposed and n = 1664/4111; 82.60% in the unexposed), with adjusted RR 1.06; 95% CI, 0.94–1.19. The mean duration of NVP symptoms was also similar between the groups.

Conclusions

This cohort study found a lower rate of HG in the preconceptional metformin-exposed group compared to unexposed, although the study was not powered to identify a significant association. Rated and durations NVP were similar between groups. These are relevant to guiding future clinical trials on the efficacy of metformin as a prophylactic agent for HG.