Pregnancy PretermPhase 4NCT04332393
Metformin to Treat Corticosteroids-induced Hyperglycemia
A Phase 4 study testing Metformin in people with Pregnancy Preterm and Glycemic Control, run by The Baruch Padeh Medical Center, Poriya at 4 sites in Israel.
Trial summary
Antenatal corticosteroids, particularly, betamethasone is routinely administered to pregnant women at risk for preterm delivery to improve neonatal outcomes. Although antenatal betamethasone was shown to induce both maternal hyperglycemia and neonatal hypoglycemia, to date, there is insufficient data to establish… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pregnancy Preterm, Glycemic Control, Corticosteroids Induced Hyperglycemia
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 187 participants
- Where
- 4 sitesIsrael
- Study dates
- 5 Jul 2020to 5 May 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pregnant women receiving betamethasone from 24 to 36.5 gestational weeks
- Before or within 24 hours following the first dose of betamethasone
- ≥18 years old
Who cannot join
- Women with pre-gestational and gestational diabetes mellitus (GDM)
- Known allergic sensitivity to metformin
- Known chronic heart failure
- Known chronic renal failure
- Refuse to participate
- Refuse to perform glucose challenge test/glucose tolerance test later on
Trial locations and contacts
4 sites in 1 country.
Israel4 sites
Emek medical center
Afula
Galilee medical center
Nahariya
Ziv medical center
Safed
Baruch Padeh Medical center, Poriya
Tiberias, North, 15208
About this study
Official title: The Effect of Metformin in Pregnant Women Who Received Antenatal Corticosteroids on Glycemic Control and the Rate of Neonatal Hypoglycemia - Multicenter Prospective Randomized, Controlled Trial
Antenatal corticosteroids, particularly, betamethasone is routinely administered to pregnant women at risk for preterm delivery to improve neonatal outcomes.
Although antenatal betamethasone was shown to induce both maternal hyperglycemia and neonatal hypoglycemia, to date, there is insufficient data to establish whether treatment for maternal hyperglycemia, particularly, metformin, will decrease the risk for neonatal hypoglycemia, particularly of preterm neonates.
In the present study the investigators will examine the effect of treatment with metformin on maternal glycemic control and hypoglycemia in preterm neonates following maternal betamethasone treatment.
- Being tested
- Metformin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin tablets according to glycemic control. Initial dose: 425 mg before meals (breakfast, lunch and supper) and 1700 mg around 22:00. Modifications may take place according to glycemic control
| Study group | Role | What they receive |
|---|---|---|
| metformin group | Experimental | Not described Receives: Drug: Metformin |
| No treatment group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean maternal daily glucose values
According to daily glucose charts
Measured: Up to 4 days
The rate of neonatal hypoglycemia in preterm deliveries (<37 gestational weeks)
Measured: Up to 7 days after delivery or discharge (which ever comes first)
Secondary outcomes (13)
Mean maternal daily pre-prandial glucose values
According to daily glucose charts
Measured: Up to 4 days
Mean maternal daily post-prandial glucose values
According to daily glucose charts
Measured: Up to 4 days
Percent of abnormal values in the daily glucose chart
According to daily glucose charts
Measured: Up to 4 days
Rate of cesarean sections and operative deliveries
Measured: At delivery
Rate of neonates who will be admitted to the neonatal intensive care unit
APGAR scale of 0-worst and 10-best
Measured: Up to a week after delivery
Apgar score at 1 and 5 minutes
Measured: At delivery
Cord blood pH levels (when taken)
Measured: At delivery
The rate of neonates with hyperbilirubinemia
Measured: Up to 7 days after delivery or discharge (which ever comes first)
Neonatal mean head circumference
Measured: Up to 7 days after delivery or discharge (which ever comes first)
Neonatal mean birth weight
Measured: at delivery
The rate of fetal malformations and developmental disorders
Measured: Up to 7 days after delivery or discharge (which ever comes first)
Mean and lowest neonatal blood glucose values in preterm neonates
Measured: Up to 7 days after delivery or discharge (which ever comes first)
The rate of maternal adverse effects
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2020
- Study start5 Jul 2020
- Primary completion7 Jul 2024
- Study completion5 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pregnancy PretermStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 187 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Baruch Padeh Medical Center, Poriya
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04332393
- Sponsor's protocol ID
- 21-20POR
- Status last verified
- May 2025
- First submitted
- 29 Mar 2020
- Last updated
- 9 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared according to the local review board regulations
Publications
Yefet E, Massalha M, Talmon G, Labay A, Matanis M, Sleman E, Nassra R, Frank Wolf M, Sgayer I, Lowenstein L, Nachum Z. Metformin, Maternal Glycemic Control, and Neonatal Hypoglycemia After Antenatal Steroids: A Randomized Clinical Trial. JAMA Netw Open. 2026 Jan 2;9(1):e2552807. doi: 10.1001/jamanetworkopen.2025.52807.
PubMed 41511771
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Metformin in Pregnant Women Who Received Antenatal Corticosteroids on Glycemic Control and the Rate of Neonatal Hypoglycemia - Multicenter Prospective Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT04332393
- Acronym / sponsor ID
- 21-20POR
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 187 participants (actual)
- Lead sponsor
- The Baruch Padeh Medical Center, PoriyaOther government
- Study start
- 5 Jul 2020 (actual)
- Primary completion
- 7 Jul 2024 (actual)
- Study completion
- 5 May 2025 (actual)
- First posted
- 2 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antenatal corticosteroids, particularly, betamethasone is routinely administered to pregnant women at risk for preterm delivery to improve neonatal outcomes.
Although antenatal betamethasone was shown to induce both maternal hyperglycemia and neonatal hypoglycemia, to date, there is insufficient data to establish whether treatment for maternal hyperglycemia, particularly, metformin, will decrease the risk for neonatal hypoglycemia, particularly of preterm neonates.
In the present study the investigators will examine the effect of treatment with metformin on maternal glycemic control and hypoglycemia in preterm neonates following maternal betamethasone treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| metformin group | Experimental | Drug: Metformin |
| No treatment group | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Pregnant women receiving betamethasone from 24 to 36.5 gestational weeks
- Before or within 24 hours following the first dose of betamethasone
- ≥18 years old
Key exclusion criteria (6 listed)
- Women with pre-gestational and gestational diabetes mellitus (GDM)
- Known allergic sensitivity to metformin
- Known chronic heart failure
- Known chronic renal failure
- Refuse to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin tablets according to glycemic control. Initial dose: 425 mg before meals (breakfast, lunch and supper) and 1700 mg around 22:00. Modifications may take place according to glycemic control | Drug | metformin group |
Primary outcome
Mean maternal daily glucose values
Time frame: Up to 4 days
According to daily glucose charts
The rate of neonatal hypoglycemia in preterm deliveries (<37 gestational weeks)
Time frame: Up to 7 days after delivery or discharge (which ever comes first)
13 secondary outcomes
Mean maternal daily pre-prandial glucose values
Time frame: Up to 4 days
Mean maternal daily post-prandial glucose values
Time frame: Up to 4 days
Percent of abnormal values in the daily glucose chart
Time frame: Up to 4 days
Rate of cesarean sections and operative deliveries
Time frame: At delivery
Rate of neonates who will be admitted to the neonatal intensive care unit
Time frame: Up to a week after delivery
Apgar score at 1 and 5 minutes
Time frame: At delivery
Cord blood pH levels (when taken)
Time frame: At delivery
The rate of neonates with hyperbilirubinemia
Time frame: Up to 7 days after delivery or discharge (which ever comes first)
Neonatal mean head circumference
Time frame: Up to 7 days after delivery or discharge (which ever comes first)
Neonatal mean birth weight
Time frame: at delivery
The rate of fetal malformations and developmental disorders
Time frame: Up to 7 days after delivery or discharge (which ever comes first)
Mean and lowest neonatal blood glucose values in preterm neonates
Time frame: Up to 7 days after delivery or discharge (which ever comes first)
The rate of maternal adverse effects
Time frame: 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2025.
- Derived from this study: PubMed 41511771Yefet E, Massalha M, Talmon G, Labay A, Matanis M, Sleman E, Nassra R, Frank Wolf M, Sgayer I, Lowenstein L, Nachum Z. Metformin, Maternal Glycemic Control, and Neonatal Hypoglycemia After Antenatal Steroids: A Randomized Clinical Trial. JAMA Netw Open. 2026 Jan 2;9(1):e2552807. doi: 10.1001/jamanetworkopen.2025.52807.
- Individual participant dataSharing planned: Yes. IPD will be shared according to the local review board regulations
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Pregnancy Preterm and Glycemic Control, run by The Baruch Padeh Medical Center, Poriya at 4 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean maternal daily glucose values (time frame: Up to 4 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04332393, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2025.