Dataset Information

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

ABSTRACT:

Importance

Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain.

Objective

To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38.

Design, setting, and participants

Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria.

Interventions

Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care.

Main outcomes and measures

The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38.

Results

Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7.

Conclusion and relevance

Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials.

Trial registration

ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

SUBMITTER: Dunne F

PROVIDER: S-EPMC10548359 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Dunne Fidelma F Newman Christine C Alvarez-Iglesias Alberto A Ferguson John J Smyth Andrew A Browne Marie M O'Shea Paula P Devane Declan D Gillespie Paddy P Bogdanet Delia D Kgosidialwa Oratile O Egan Aoife A Finn Yvonne Y Gaffney Geraldine G Khattak Aftab A O'Keeffe Derek D Liew Aaron A O'Donnell Martin M

JAMA 20231001 16

<h4>Importance</h4>Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain.<h4>Objective</h4>To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38.<h4>Design, setting, and participants</h4>Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through Septe ...[more]

PMID: 37786390

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Project description:BackgroundGestational diabetes mellitus is common and is associated with an increased risk of adverse maternal and perinatal outcomes. Although experts recommend universal screening for gestational diabetes, consensus is lacking about which of two recommended screening approaches should be used.MethodsWe performed a pragmatic, randomized trial comparing one-step screening (i.e., a glucose-tolerance test in which the blood glucose level was obtained after the oral administration of a 75-g glucose load in the fasting state) with two-step screening (a glucose challenge test in which the blood glucose level was obtained after the oral administration of a 50-g glucose load in the nonfasting state, followed, if positive, by an oral glucose-tolerance test with a 100-g glucose load in the fasting state) in all pregnant women who received care in two health systems. Guidelines for the treatment of gestational diabetes were consistent with the two screening approaches. The primary outcomes were a diagnosis of gestational diabetes, large-for-gestational-age infants, a perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury), gestational hypertension or preeclampsia, and primary cesarean section.ResultsA total of 23,792 women underwent randomization; women with more than one pregnancy during the trial could have been assigned to more than one type of screening. A total of 66% of the women in the one-step group and 92% of those in the two-step group adhered to the assigned screening. Gestational diabetes was diagnosed in 16.5% of the women assigned to the one-step approach and in 8.5% of those assigned to the two-step approach (unadjusted relative risk, 1.94; 97.5% confidence interval [CI], 1.79 to 2.11). In intention-to-treat analyses, the respective incidences of the other primary outcomes were as follows: large-for-gestational-age infants, 8.9% and 9.2% (relative risk, 0.95; 97.5% CI, 0.87 to 1.05); perinatal composite outcome, 3.1% and 3.0% (relative risk, 1.04; 97.5% CI, 0.88 to 1.23); gestational hypertension or preeclampsia, 13.6% and 13.5% (relative risk, 1.00; 97.5% CI, 0.93 to 1.08); and primary cesarean section, 24.0% and 24.6% (relative risk, 0.98; 97.5% CI, 0.93 to 1.02). The results were materially unchanged in intention-to-treat analyses with inverse probability weighting to account for differential adherence to the screening approaches.ConclusionsDespite more diagnoses of gestational diabetes with the one-step approach than with the two-step approach, there were no significant between-group differences in the risks of the primary outcomes relating to perinatal and maternal complications. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ScreenR2GDM ClinicalTrials.gov number, NCT02266758.).

Project description:BackgroundAlthough in 2013 the American College of Obstetricians and Gynecologists recommended early screening for gestational diabetes in obese women, no studies demonstrate an improvement in perinatal outcomes with this strategy.ObjectiveWe sought to determine whether early screening for gestational diabetes improves perinatal outcomes in obese women.Materials and methodsRandomized controlled trial comparing early gestational diabetes screening (14-20 weeks) to routine screening (24-28 weeks) in obese women (body mass index ≥30 kg/m2) at 2 tertiary care centers in the United States. Screening was performed using a 50-g, 1-hour glucose challenge test followed by a 100-g, 3-hour glucose tolerance test if the initial screen was ≥135 mg/dL. Gestational diabetes was diagnosed using Carpenter-Coustan criteria. Women not diagnosed at 14 to 20 weeks were rescreened at 24 to 28 weeks. Exclusion criteria were pre-existing diabetes, major medical illness, bariatric surgery, and prior cesarean delivery. The primary outcome was a composite of macrosomia (>4000 g), primary cesarean delivery, hypertensive disease of pregnancy, shoulder dystocia, neonatal hyperbilirubinemia, and neonatal hypoglycemia (assessed within 48 hours of birth).ResultsA total of 962 women were randomized, and outcomes were available for 922. Of these 922 women, 459 (49.8%) were assigned to early screen and 463 (50.2%) to routine screen. Baseline characteristics were balanced between groups. In the early screening group, 69 (15.0%; 95% confidence interval, 11.9-18.6%) were diagnosed with gestational diabetes: 29 (6.3%; 95% confidence interval, 4.3-8.9%) at <20 weeks and 40 (8.7%; 95% confidence interval, 6.3-11.7%) at >24 weeks. Of those randomized to routine screening, 56 (12.1%; 95% confidence interval, 9.3-15.4%) had gestational diabetes. Early screening did not reduce the incidence of the primary outcome (56.9% in the early screen versus 50.8% in the routine screen, P = .07; relative risk, 1.12; 95% confidence interval, 0.99-1.26).ConclusionEarly screening for gestational diabetes in obese women did not reduce the composite perinatal outcome.

Dataset Information

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusion and relevance

Trial registration

Publications

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Similar Datasets

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