A Phase 3 interventional study of Metformin ER and Placebo in Preeclampsia, sponsored by Lina Bergman. Recruiting at 18 sites in 3 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Lina Bergman · Phase 3, Interventional, and Treatment
Preterm preeclampsia is a severe condition for both the mother and the fetus. Currently, the only treatment available to stop disease progression is termination/delivery of the fetus and placenta. Therefore, preterm preeclampsia carries the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth. There is evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition. This multi centre double blind randomised controlled trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Nordic setting.
Preeclampsia is globally responsible for 60,000 maternal deaths per year, and far greater numbers of fetal losses. Preterm preeclampsia is a severe variant with the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth (clinicians are forced to deliver the baby preterm for maternal or fetal health reasons).
There is preclinical evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition.
Previous research from the Preeclampsia Intervention 2 trial (PI2) show that metformin was able to delay delivery in early preterm preeclampsia. Metformin extended release (ER) was associated with a median 7.6-day prolongation of pregnancy (geometric mean ratio (GMR) 1.39 (95% CI 0.99 to 1.96) P=0.057).Trends towards increased birthweight (mean difference 110gm (95%CI -80 to 300), a decreased length of stay at the neonatal intensive care unit (median difference 5.0 days less; GMR 0.86, 95% CI 0.62 to 1.2) and a shorter period of admission in any neonatal ward (median difference 12.0 days less; GMR 0.82, 95% CI 0.57 to 1.18) in the metformin ER group were found. Importantly, while gastrointestinal side effects were common, no serious adverse events related to trial medications were observed.
The PI 2 trial has shown that metformin may be a disease modifying treatment for preterm preeclampsia. The trial is being repeated in a larger scale in the PI3 trial in South Africa to also assess neonatal outcomes. In the Nordic countries, the demographics of the population are different and expectant management of preeclampsia allows for the women to reach 37 weeks of gestation as opposed to 34 weeks of gestation in the PI2 trial. This trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Nordic setting. Follow up of mothers and children will be carried out two years post partum.
916 studies on the registry are indexed under Pre-Eclampsia; 243 are open to participants now.
This study's planned enrollment of 294 is above the median of 110 across 480 interventional studies indexed under Pre-Eclampsia.
Browse Pre-Eclampsia studies →This is the only study on the registry with Lina Bergman as lead sponsor.
Counted across the registry records on this site, refreshed daily.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metformin ER oral tablet 500 mg three times daily and increased to one gram (two tablets) three times daily as tolerated.
Drug: Metformin ER
1 placebo tablet three times daily and increased to 2 placebo tablets three times daily as tolerated.
Drug: Placebo
Metformin ER, one gram three times daily taken orally. Once the participants have been recruited, they will start by taking one 500 mg tablet three times a day. If well tolerated it will be increased day two to a maximum of two tablets three times a day. Treatment will continue until delivery. If there are side effects that are not tolerable, the dose will be decreased and the participant will remain blinded. Each participant will keep a treatment diary and number of tablets taken will be documented by the participant or hospital staff. The study will not alter or interfere with treatment or care routinely given for preterm preeclampsia.
Also known as: Glucophage SR 500 mg prolonged release tablets
Placebo, two tablets three times daily taken orally. Once the participants have been recruited, they will start by taking one tablet three times a day. If well tolerated it will be increased day two to a maximum of two tablets three times a day. Treatment will continue until delivery. If there are side effects that are not tolerable, the dose will be decreased and the participant will remain blinded. Each participant will keep a treatment diary and number of tablets taken will be documented by the participant or hospital staff. The study will not alter or interfere with treatment or care routinely given for preterm preeclampsia.
Pregnancy prolongation
Length of pregnancy from diagnosis of preeclampsia to delivery
Time frame: From randomisation to delivery, measured in days and hours, up to 105 days
Time for neonatal care
Time for neonatal care from birth to discharge
Time frame: From birth to discharge from neonatal care, measured in days and hours, up to 126 days
Neonatal birth weight
Birth wight measured in grams
Time frame: At birth
Occurrence of maternal death
Occurrence of maternal death
Time frame: Registered from inclusion to two month post partum
Occurrence of Eclampsia
Occurrence of Eclampsia
Time frame: Registered from inclusion to two month post partum
Occurrence of Cerebral vascular event
Occurrence of Cerebral vascular event
Time frame: Registered from inclusion to two month post partum
Occurrence of posterior reversible encephalopathy syndrome
Occurrence of posterior reversible encephalopathy syndrome
Time frame: Registered from inclusion to two month post partum
Occurrence of pulmonary edema
Occurrence of pulmonary edema
Time frame: Registered from inclusion to two month post partum
Occurrence of left ventricular failure
Occurrence of left ventricular failure
Time frame: Registered from inclusion to two month post partum
Occurrence of renal dialysis
Occurrence of renal dialysis
Time frame: Registered from inclusion to two month post partum
Occurrence of renal failure
Occurrence of renal failure:≥ 90 µmol/L or no urinary output for 6 hours
Time frame: Registered from inclusion to two month post partum
Occurrence of elevated liver transaminases
Occurrence of elevated liver transaminases: ALT or AST ≥ 2 times highest normal value (ALAT \>1.5 µkat/L and ASAT \> 1.2 µkat/L)
Time frame: Registered from inclusion to two month post partum
Occurrence of HELLP syndrome
Occurrence of HELLP (Haemolysis, elevated liver enzymes and low platelets) syndrome
Time frame: Registered from inclusion to two month post partum
Occurrence of thrombocytopenia
Occurrence of thrombocytopenia (platelets \<100 X 109/L)
Time frame: Registered from inclusion to two month post partum
Occurrence of liver haematoma or rupture
Occurrence of liver haematoma or rupture
Time frame: Registered from inclusion to two month post partum
Occurrence of admission to an intensive care unit
Occurrence of admission to an intensive care unit
Time frame: Registered from inclusion to two month post partum
Occurrence of severe hypertension
Occurrence of severe hypertension (BP\>160/110 mm Hg)
Time frame: Registered from inclusion to two month post partum
Occurrence of disseminated intravascular coagulation
Occurrence of disseminated intravascular coagulation
Time frame: Registered from inclusion to two month post partum
Occurrence of caesarean section
Occurrence of caesarean section
Time frame: At birth
Occurrence of major postpartum hemorrhage
Occurrence of major postpartum hemorrhage (\>1000 ml)
Time frame: At birth
Occurrence of thromboembolic disease
Occurrence of thromboembolic disease: deep venous thrombosis or pulmonary embolism
Time frame: Registered from inclusion to two month post partum
Duration of maternal postpartum hospital stay
Duration of maternal postpartum hospital stay (days)
Time frame: Registered from birth to hospital discharge
Number of antihypertensive drugs
Number of antihypertensive drugs at discharge after delivery
Time frame: At discharge
Duration of antihypertensive medication
Duration of antihypertensive medication (days)
Time frame: From inclusion to two month postpartum
Occurrence of intrauterine fetal demise
Occurrence of intrauterine fetal demise
Time frame: From inclusion to birth
Occurrence of neonatal death
Occurrence of neonatal death
Time frame: From inclusion to two month post partum
Occurrence of growth restriction at birth
Occurrence of growth restriction at birth (less than 2 standard deviations from median weight from Swedish birth weight growth curves).
Time frame: At birth
Occurrence of grade 3 or 4 intraventricular hemorrhage
Occurrence of grade 3 or 4 intraventricular hemorrhage
Time frame: Registered from birth to two month post partum
Occurrence of necrotizing enterocolitis
Occurrence of necrotizing enterocolitis
Time frame: Registered from birth to two month post partum
Occurrence of reversed a-wave in the ductus venosus
Occurrence of reversed a-wave in the ductus venosus
Time frame: Registered from birth to two month post partum
Occurrence of persistent reversed flow in the umbilical artery
Occurrence of persistent reversed flow in the umbilical artery
Time frame: Registered from inclusion to birth
Occurrence of redistribution in the middle cerebral artery
Occurrence of redistribution in the middle cerebral artery
Time frame: Registered from birth to two month post partum
Occurrence of low APGAR score
Occurrence of low APGAR score, defined as less than 4 at 5 minutes
Time frame: At birth
Occurrence of umbilical artery pH below 7.1
Occurrence of umbilical artery pH below 7.1
Time frame: At birth
Occurrence of invasive ventilation, intubation and mechanical ventilation or non-invasive ventilatione outcome
Occurrence of invasive ventilation, intubation and mechanical ventilation or non-invasive ventilation; continuous positive airway pressure (CPAP) support or high flow nasal oxygen
Time frame: Registered from birth to two month post partum
Occurrence of grade III/IV hyaline membrane disease
Occurrence of grade III/IV hyaline membrane disease
Time frame: Registered from birth to two month post partum
Occurrence of surfactant use
Occurrence of surfactant use
Time frame: Registered from birth to two month post partum
Occurrence of retinopathy of prematurity
Occurrence of retinopathy of prematurity
Time frame: Registered from birth to two month post partum
Occurrence of neonatal sepsis
Occurrence of neonatal sepsis
Time frame: Registered from birth to two month post partum
Tolerability and safety
Severity of nausea measured by PHASE-20 Severity of vomiting measured by PHASE-20 Severity of diarrhoea measured by PHASE-20 Severity of headache measured by PHASE-20
Time frame: From inclusion to birth
Tolerability and safety
Occurrence of lactic acidosis (blood pH\< 7.35 or blood lactate\> 5 mM)
Time frame: From inclusion to birth
Tolerability and safety
Drug adherence (measured by treatment diary)
Time frame: From inclusion to birth
Pre-eclampsia-related biomarkers
Concentrations of Soluble Fms-like tyrosine kinase-1 Concentrations of Placental growth factor Concentrations of Soluble endoglin
Time frame: From inclusion to two years post partum
Gut and vaginal microbiome composition
Omics-based analysis of the microbiome
Time frame: From inclusion to two years post partum
Breastfeeding initiation
Breastfeeding initiation (measured by unvalidated breastfeeding questionnaire with no score)
Time frame: From birth to two month postpartum
Depressive symptoms
Depressive symptoms (measured by the Edinburgh Postnatal Depression Scale; 0-30, with higher scores indicating higher self-esteem)
Time frame: From inclusion to two years post partum
Self-esteem
Self-esteem (measured by The Rosenberg Self-Esteem Scale; 0-30, higher scores indicating higher self-esteem)
Time frame: From inclusion to two years post partum
Perceived stress
Perceived stress (measured by the 10-item Perceived Stress Scale; 0-40, with higher scores indicating greater perceived stress)
Time frame: From inclusion to two years postpartum
Breastfeeding self-efficacy
Breastfeeding self-efficacy (measured by the Breastfeeding Self-Efficacy Scale-Short Form; 14-70, higher score= greater breastfeeding self-efficacy)
Time frame: From birth to two month postpartum
Health-related quality of life
Health-related quality of life (measured using the EQ-5D-5L (the official name) and reported as the EQ-5D-5L index value and the EQ VAS \[0-100\]). EQ-5D-5L index values will be derived using country-specific value sets where available; higher index values indicate better health-related quality of life. The EQ VAS ranges from 0 to 100, with higher scores indicating better self-rated health)
Time frame: From inclusion to two years post partum
Parental-infant bonding
Parental-infant bonding (measured by the Postpartum Bonding Questionnaire; 0-125, higher score= greater impairment/difficulties in parent-infant bonding)
Time frame: From birth to two month post partum
Health economic outcomes
Cost-effectiveness short-term: direct healthcare costs (based on drug and healthcare use) for mother and child from enrolment until discharge, will be compared to incremental effects measured as prolongation of gestation Cost-effectiveness long-term: societal costs (based on drug and healthcare use, and social insurance transactions) for mother and child from enrolment until two years postpartum, will be compared to incremental effects measured as prolongation of gestation and health-related quality of life
Time frame: From birth to two years post partum
Risk of autism spectrum disorder
Risk of autism spectrum disorder (evaluated by the Modified Checklist for Autism in Toddlers, Revised (M-CHAT/R); 20 questions resulting in score 0-20 where 0-2 indicates no risk, 3-7 moderate risk and 8-20 high risk for autism).
Time frame: At two years corrected age
Cognitive development of the child
Developmental screening (based on parental questionnaire Ages and Stages Questionnaire, Third Edition 24-months (ASQ-3);questions covering five key developmental domains; communication, gross motor, fine motor, problem-solving and personal-social skills; answers scored from 0-60 with age-specific cut-off levels at -2 and -1SD indicating clear or suspect developmental delay)
Time frame: At two years corrected age
Cognitive development of the child
Comprehensive developmental assessment (evaluated by the Bayley Scales of Infant Development-4 (BSID-4), with main scores for motor, language and cognitive function. Results expressed as age-corrected developmental scores in each domain with clear developmental delay at scores \< 70 (-2SD) and suspect developmental delay at scores \< 85 (-1SD).
Time frame: At two years corrected age
Plan to share: Yes — Metadata and statistical code will be published in public repositories upon release of the trial's primary results. Deidentified data may be shared upon reasonable request following a written application including a research proposal and ethical approval, in accordance with applicable ethical and legal requirements. We plan to share data with similar ongoing or planned trials in South Africa and The Netherlands.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Metformin