{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["333(6)"],"submitter":["Rademaker D"],"pubmed_abstract":["<h4>Importance</h4>Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.<h4>Objective</h4>To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.<h4>Design, setting, and participants</h4>Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing).<h4>Interventions</h4>Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets.<h4>Main outcomes and measures</h4>The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission.<h4>Results</h4>Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups.<h4>Conclusions and relevance</h4>Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age.<h4>Trial registration</h4>Netherlands Trial Registry Identifier: NTR6134."],"journal":["JAMA"],"pagination":["470-478"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11815519"],"repository":["biostudies-literature"],"pubmed_title":["Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial."],"pmcid":["PMC11815519"],"pubmed_authors":["van der Made FW","van Houtum WH","Braams-Lisman BAM","van Bemmel T","Evers IM","de Valk HW","Oosterwerff MM","Klooker TK","van den Beld AW","Daemen-Gubbels CRGM","van Rijn BB","Vlug AG","Rademaker D","Hermes W","van Bon AC","Krabbendam I","Belle-van Meerkerk G","Sueters M","Nijkamp JW","Scholten R","Siegelaar SE","Meijer RI","van Laar JOEH","Wouters-van Poppel P","SUGAR-DIP Study Group","Diekman MJM","Verdonk K","Assouiki F","DeVries JH","Eskes SA","Sanson-van Praag ME","Vogelvang TE","Duijnhoven RG","Akerboom BMC","Zandstra M","Kiewiet-Kemper RM","van Wijk JPH","de Koning EJP","Wouters MGAJ","Galjaard S","IJzerman RG","Johannsson-Vidarsdottir S","van den Akker ES","Lub A","Verwij-Didden MAL","Painter RC","Franx A","Huisjes AJM","Brouwer CB","Reiss I","Wijnberger LDE","van der Post JAM","de Wit L","Bosmans JE","Hermsen BB","van Leeuwen M","Dullemond RC","Nijman RGW","Wijbenga JAM","Mol BW","Stekkinger E","Voormolen DN","Jansen HJ","Kuppens SM"],"additional_accession":[]},"is_claimable":false,"name":"Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.","description":"<h4>Importance</h4>Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.<h4>Objective</h4>To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.<h4>Design, setting, and participants</h4>Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing).<h4>Interventions</h4>Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets.<h4>Main outcomes and measures</h4>The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission.<h4>Results</h4>Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups.<h4>Conclusions and relevance</h4>Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age.<h4>Trial registration</h4>Netherlands Trial Registry Identifier: NTR6134.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-08T05:14:35.496Z","creation":"2025-07-28T03:04:01.829Z"},"accession":"S-EPMC11815519","cross_references":{"pubmed":["39761054"],"doi":["10.1001/jama.2024.23410"]}}