Hyperemesis Gravidarum Risk Reduction With Metformin

Recruiting now · Phase 1/Phase 2

Conditions studied: Hyperemesis Gravidarum

In brief

The goal of this clinical trial is to evaluate whether daily oral metformin extended-release (metformin-XR), taken prior to and in early pregnancy, can reduce the risk and severity of Hyperemesis Gravidarum (HG), a severe nausea and vomiting condition in pregnancy, in individuals aged 18-49 who have experienced HG in a previous pregnancy and are trying to conceive. Researchers also aim to better understand which individuals may respond well - or poorly - to metformin based on biological and clinical characteristics. The main questions this study aims to answer are: 1. Is metformin-XR well-tolerated when taken by non-pregnant individuals who have had HG in a previous pregnancy and are currently trying to conceive? 2. How safe and tolerable is metformin-XR when taken at increasing doses over an 8-week titration period and continued through early pregnancy (or for up to 12 months after reaching maintenance dose if pregnancy does not occur)? 3. Among those who become pregnant during the study, does pre-pregnancy metformin-XR use reduce the risk of HG coming back and lower the severity of nausea and vomiting symptoms? 4. How does pre-pregnancy metformin-XR use affect pregnancy outcomes, postpartum health, and newborn health and development? 5. Are there specific genetic, biomarker, demographic, or clinical features that predict whether someone is likely to benefit from metformin-XR or experience side effects that lead them to stop taking it? Researchers will compare a metformin treatment group to a survey-only group (comparator, no study drug) to see if metformin-XR is associated with improved outcomes, including reduced HG recurrence and better maternal and neonatal health indicators. Participants will: Complete online questionnaires before pregnancy, during early pregnancy, and postpartum (Treatment group only) Take daily metformin-XR and attend three brief study visits (Treatment group only) Undergo blood draws at specified timepoints to assess safety and biological response

Key facts

Study ID: NCT07129473
Run by: University of Southern California
People needed: 224
Starts: 2026-07-13
Expected to finish: 2031-03-01
Last updated by the study team: 2026-07-22

Who can join

Age: 18 and older, up to 49. Sex: female. Healthy volunteers: accepted.

You may qualify if…

Ages 18-49
HG in prior pregnancy (clinical criteria: intravenous (IV) fluid treatment)
Trying to conceive
Treatment Arm: willing to refrain from trying to conceive during their metformin dose titration period and before 2 weeks at maximum tolerated dose (up to 8 weeks total). Will use birth control or contraceptive device until maintenance dose.
Under care of a personal OB/GYN or willing to establish care with a personal OB/GYN before study start
Ownership of a personal scale (or willingness to obtain one for study use)
Willing to participate in a trial that includes daily use of an oral agent prior to pregnancy
Treatment Arm: residing in California/Alabama
Treatment Arm: normal blood panel (CBC) (e.g., white count, hemoglobin, platelets all within the normal range)
Treatment Arm: normal to mildly decreased creatinine levels (estimated GFR > 60 mL/min/1.73m²)
Survey/Comparator Arm: not currently taking metformin and do not plan to take metformin prior to pregnancy
Able and willing to provide written informed consent prior to initiation of any study procedures.
Demonstrates understanding of the study objectives, requirements, potential risks, and willingness to comply with study procedures and follow-up.
English speaking
Regular cycles

You may not qualify if…

Allergic or adverse reaction to metformin-XR
Thalassemia
Cirrhosis and/or hepatic impairment
Decompensated heart failure
Daily/regular use of medications/substances (tobacco, cyclobenzaprine, cannabis, escitalopram, sertraline, other SSRIs, Lasix)
Treatment Arm: Use of insulin, sulfonylureas, meglitinides, or other blood sugar altering medication
Assisted Reproductive Technology
Excess alcohol consumption (> 7 standard drinks per week on average)
Pregnant
Not trying to conceive
Treatment Arm: Residing outside California/Alabama
Treatment Arm: abnormal blood panel (CBC) (e.g., white count or platelets not within the normal range)
Treatment Arm: abnormal creatinine levels (estimated GFR < 60 mL/min/1.73m² excluded from the study, signs of kidney disease)
Treatment Arm: current metformin use
Survey/Comparator Arm: current metformin use or plans to take metformin prior to pregnancy
Any medical/surgical condition that the investigator feels would compromise the participant's participation in the study
Not able and willing to provide written informed consent prior to initiation of any study procedures.
Does not demonstrate understanding of the study objectives, requirements, potential risks, and willingness to comply with study procedures and follow-up.
Not english speaking
Irregular cycles
Not willing to refrain from trying to conceive/use birth control or contraceptive device until maintenance dose.

Where it is running

University of Southern California - Keck School of Medicine — Los Angeles, California, United States (enrolling)
The Morning Sickness & HG Clinic — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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