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Abstract

Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication associated with an increased risk of maternal and neonatal complications compared with non-diabetic pregnancies. Pharmacological treatments, such as glibenclamide, are expected to provide optimal glycemic control and reduce these risks. However, concerns regarding its safety persist and some regulatory agencies have not approved glibenclamide for GDM treatment. This systematic review and meta-analysis aimed to synthesize the most recent evidence on the efficacy and safety of glibenclamide compared with insulin in the management of GDM, with a focus on maternal and neonatal outcomes based on the most recent RCT. The objective is to provide updated insight and strengthen the evidence based supporting the use of glibenclamide as treatment option for GDM. Relevant studies were identified from Pubmed, Scopus, and CENTRAL databases, resulting in 11 randomized controlled trials (RCTs) involving 2,019 participants. The pooled analysis found that glibenclamide significantly increases the risk of neonatal hypoglycemia [RR 1.65; 95% CI 1.23 to 2.22; p-value 0.0009] and significantly decreases the risk of neonatal respiratory distress syndrome (NRDS) [RR 0.56; 95% CI 0.33 to 0.95; p-value 0.03], compared to insulin. No significant differences were observed in other maternal and neonatal outcomes between the two treatments. In conclusion, glibenclamide demonstrated comparable efficacy and safety to insulin in the management of GDM, making it a viable treatment option alongside insulin.

References

Affres, H., Victoire Senat, M., Letourneau, A., Deruelle, P., Coustols-Valat, M., Bouchghoul, H., Bouyer, J., Senat, M.-V., & Coustols-valat, M. (2021). Glyburide Therapy for Gestational Diabetes: Glycaemic Control, Maternal Hypoglycaemia, and Treatment Failure. Diabetes & Metabolism, 47(4). https://doi.org/10.1016/j.diabet.2020.11.002ï

Alemu, A. Y., Belay, G. M., Berhanu, M., & Minuye, B. (2020). Determinants of Neonatal Mortality at Neonatal Intensive Care Unit in Northeast Ethiopia: Unmatched Case-Control Study. Tropical Medicine and Health, 48(1). https://doi.org/10.1186/s41182-020-00232-9

American Diabetes Association. (2022). Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45, S232–S243. https://doi.org/10.2337/dc22- S015

American Diabetes Association Professional Practice Committee. (2024a). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024. Diabetes Care, 47, S20–S42. https://doi.org/10.2337/dc24-S002

American Diabetes Association Professional Practice Committee. (2024b). Management of Diabetes in Pregnancy: Standards of Care in Diabetes—2024. Diabetes Care, 47, S282–S294. https://doi.org/10.2337/dc24-S015

Behrashi, M., Samimi, M., Ghasemi, T., Saberi, F., & Atoof, F. (2016). Comparison of Glibenclamide and Insulin on Neonatal Outcomes in Pregnant Women with Gestational Diabetes. International Journal of Preventive Medicine, 2016-June. https://doi.org/10.4103/2008-7802.184502

Bouchghoul, H., Alvarez, J. C., Verstuyft, C., Bouyer, J., & Senat, M. V. (2020). Transplacental Transfer of Glyburide in Women with Gestational Diabetes and Neonatal Hypoglycemia Risk. PLoS ONE, 15(5). https://doi.org/10.1371/journal.pone.0232002

Brandsma, E., Christ, L. A., & Duncan, A. F. (2024). The High-Risk Infant. In Robert M. Kliegman, Joseph W. St Geme, Nathan J. BlumRobert C. Tasker, Karen M. Wilson, Abigail M. Schuh, & Cara L. Mack (Eds.), Nelson Textbook of Pediatrics (22nd ed., pp. 1038–1050). Elsevier.

Committee on Practice Bulletins—Obstetrics. (2013). Practice Bulletin No 137. Obstetrics & Gynecology, 122(2), 406–416.

Deeks, J. J., Higgins, J. P., & Altman, D. G. (2024). Analysing Data and Undertaking Meta-Analyses. In J. Higgins & J. Thomas (Eds.), Cochrane Handbook for Systematic Reviews of Interventions Version 6.5 (updated August 2024). Cochrane. www.training.cochrane.org/handbook

Díaz, P., Dimasuay, K. G., Koele-Schmidt, L., Jang, B., Barbour, L. A., Jansson, T., & Powell, T. L. (2017). Glyburide Treatment in Gestational Diabetes is Associated with Increased Placental Glucose Transporter 1 Expression and Higher Birth Weight. Placenta, 57, 52–59. https://doi.org/10.1016/j.placenta.2017.05.016

Downing, N. S., Aminawung, J. A., Shah, N. D., Krumholz, H. M., & Ross, J. S. (2014). Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012. JAMA, 311(4), 368–377. https://doi.org/10.1001/jama.2013.282034

Egan, A. M., & Dinneen, S. F. (2022). Classification and Diagnosis of Diabetes Mellitus. In R. Paul Robertson (Ed.), DeGroot’s Endocrinology (8th ed., Vol. 1). Elsevier.

Elsayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Leon, J., Lyons, S. K., Perry, M. Lou, Prahalad, P., Pratley, R. E., Seley, J. J., Stanton, R. C., & Gabbay, R. A. (2023). Management of Diabetes in Pregnancy: Standards of Care in Diabetes—2023. Diabetes Care, 46, S254–S266. https://doi.org/10.2337/dc23-S015

Faraji, A., Tahamtani, L., Maharlouei, N., & Asadi, N. (2023). Effects of Oral Glibenclamide Versus Subcutaneous Insulin on Perinatal Outcome of Patients with Gestational Diabetes Mellitus: A Randomized Clinical Trial. Obstetric Medicine, 16(2), 98–103. https://doi.org/10.1177/1753495X221100167

Hod, M., Kapur, A., Sacks, D. A., Hadar, E., Agarwal, M., Di Renzo, G. C., Cabero Roura, L., McIntyre, H. D., Morris, J. L., & Divakar, H. (2015). The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics, 131 Suppl 3, S173–S211. https://doi.org/10.1016/S0020-7292(15)30033-3

Karkia, R., Giacchino, T., Shah, S., Gough, A., Ramadan, G., & Akolekar, R. (2023). Gestational Diabetes Mellitus: Association with Maternal and Neonatal Complications. Medicina (Lithuania), 59(12). https://doi.org/10.3390/medicina59122096

Kimber-Trojnar, Ż., Marciniak, B., Patro-Małysza, J., Skórzyńska-Dziduszko, K., Poniedziałek- Czajkowska, E., Mierzyński, R., Gałczyński, K., Trojnar, M., Leszczyńska-Gorzelak, B., & Oleszczuk, J. (2014). Is Glyburide Safe in Pregnancy? Current Pharmaceutical Biotechnology, 15, 100–112.

Langer, O., Conway, D. L., Berkus, M. D., Xenakis, E. M.-J., & Gonzales, O. (2000). A Comparison of Glyburide and Insulin In Women with Gestational Diabetes Mellitus. The New England Journal of Medicine, 343, 1134–1138. https://doi.org/10.1056/NEJM200010193431601

Langer, O., Yogev, Y., Xenakis, E. M. J., & Rosenn, B. (2005). Insulin and Glyburide Therapy: Dosage, Severity Level of Gestational Diabetes, and Pregnancy Outcome. American Journal of Obstetrics and Gynecology, 192(1), 134–139. https://doi.org/10.1016/j.ajog.2004.07.011

Li, C., Gao, C., Zhang, X., Zhang, L., Shi, H., & Jia, X. (2022). Comparison of the Effectiveness and Safety of Insulin and Oral Hypoglycemic Drugs in the Treatment of Gestational Diabetes Mellitus: A Meta-Analysis of 26 Randomized Controlled Trials. Gynecological Endocrinology, 38(4), 303–309. https://doi.org/10.1080/09513590.2021.2015761

Logue, T. C., & Sciscione, A. (2024). Gestational Diabetes Mellitus (GDM). In F. F. Ferri (Ed.), Ferri’s Clinical Advisor 2025. Elsevier.

Mirzamoradi, M., Heidar, Z., Faalpoor, Z., Naeiji, Z., & Jamali, R. (2015). Comparison of Glyburide and Insulin in Women with Gestational Diabetes Mellitus and Associated Perinatal Outcome: a Randomized Clinical Trial. Acta Medica Iranica, 53(2), 97–103.

Moore, T. R., Powe, C. E., & Catalano, P. (2022). Diabetes in Pregnancy. In C. J. Lockwood, T. Moore, J. Copel, R. M. Silver, R. Resnik, L. Dugoff, & J. Louis (Eds.), Creasy and Resnik’s Maternal-Fetal Medicine (9th ed.).

Mukerji, G., & Feig, D. S. (2017). Pharmacological Management of Gestational Diabetes Mellitus. Drugs, 77(16), 1723–1732. https://doi.org/10.1007/s40265-017-0807-0

Mukherjee, S. M., & Dawson, A. (2022). Diabetes: How to Manage Gestational Diabetes Mellitus. Drugs in Context, 11. https://doi.org/10.7573/dic.2021-9-12

Nankervis, A., & Conn, J. (2013). Gestational Diabetes Mellitus. Australian Journal for General Practitioners, 42, 528–531.

Negash, Z., Tadiwos, A., Urgessa, E. M., Gebretekle, G. B., Abebe, E., & Fentie, A. M. (2023). Insulin Injection Practice and Health Related Quality of Life Among Individuals with Diabetes at Tikur Anbessa Specialized Hospital, Ethiopia: A Cross-Sectional Study. Health and Quality of Life Outcomes, 21(1). https://doi.org/10.1186/s12955-023-02123-z

Salazar-Petres, E. R., & Sferruzzi-Perri, A. N. (2022). Pregnancy-Induced Changes in β-Cell Function: What are the Key Players? In Journal of Physiology (Vol. 600, Issue 5, pp. 1089– 1117). John Wiley and Sons Inc. https://doi.org/10.1113/JP281082

Schwartz, R. A., Rosenn, B., Aleksa, K., & Koren, G. (2015). Glyburide Transport Across the Human Placenta. Obstetrics and Gynecology, 125(3), 583–588. https://doi.org/10.1097/AOG.0000000000000672

Sénat, M., Helene, A., Letourneau, A., Coustols-Valat, M., Cazaubiel, M., Legardeur, helene, Jacquier, J., Bourcigaux, N., Simon, E., Rod, A., Héron, I., Castera, V., Sentilhes, L., Bretelle, F., Rolland, C., Morin, M., Deruelle, P., De Carne, C., Maillot, F., … Desbriere, R. (2018). Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial. JAMA, 319(17). https://doi.org/doi: 10.1001/jama.2018.4072

Sharma, A. K., Singh, S., Singh, H., Mahajan, D., Kolli, P., Mandadapu, G., Kumar, B., Kumar, D., Kumar, S., & Jena, M. K. (2022). Deep Insight of the Pathophysiology of Gestational Diabetes Mellitus. In Cells (Vol. 11, Issue 17). MDPI. https://doi.org/10.3390/cells11172672

Song, R., Chen, L., Chen, Y., Si, X., Liu, Y., Liu, Y., Irwin, D. M., & Feng, W. (2017). Comparison of Glyburide and Insulin in the Management of Gestational Diabetes: A Meta-Analysis. PLoS ONE, 12(8). https://doi.org/10.1371/journal.pone.0182488

Sterne, J. A. C., Savović, J., Page, M. J., Elbers, R. G., Blencowe, N. S., Boutron, I., Cates, C. J., Cheng, H. Y., Corbett, M. S., Eldridge, S. M., Emberson, J. R., Hernán, M. A., Hopewell, S., Hróbjartsson, A., Junqueira, D. R., Jüni, P., Kirkham, J. J., Lasserson, T., Li, T., … Higgins, J. P. T. (2019). RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials. The BMJ, 366. https://doi.org/10.1136/bmj.l4898

Stylianou-Riga, P., Boutsikou, T., Kouis, P., Kinni, P., Krokou, M., Ioannou, A., Siahanidou, T., Iliodromiti, Z., Papadouri, T., Yiallouros, P. K., & Iacovidou, N. (2021). Maternal and Neonatal Risk Factors for Neonatal Respiratory Distress Syndrome in Term Neonates in Cyprus: A Prospective Case–Control Study. Italian Journal of Pediatrics, 47(1). https://doi.org/10.1186/s13052-021-01086-5

The International Diabetes Federation (IDF). (2023). The IDF Approach for Care and Management of Gestational Diabetes Mellitus. www.idf.org/wings

Tierney, J. F., Stewart, L. A., & Clarke, M. (2024). Individual Participant Data. In J. Higgins & J. Thomas (Eds.), Cochrane Handbook for Systematic Reviews of Interventions Version 6.5 (updated August 2024). www.training.cochrane.org/handbook.

Toledano, Y., Hadar, E., & Hod, M. (2018). Pharmacotherapy for Hyperglycemia in Pregnancy – The New Insulins. Diabetes Research and Clinical Practice, 145, 59–66. https://doi.org/10.1016/j.diabres.2018.04.035

Trujillo, J., & Haines, S. (2023). Diabetes Mellitus. In J. T. DiPiro, G. C. Yee, S. T. Haines, T. D. Nolin, V. L. Ellingrod, & L. M. Posey (Eds.), DiPiro’s Pharmacotherapy: A Pathophysiologic Approach (12th ed.). McGraw Hill.

Wang, X., Liu, W., Chen, H., & Chen, Q. (2021). Comparison of Insulin, Metformin, and Glyburide on Perinatal Complications of Gestational Diabetes Mellitus: A Systematic Review and Meta- Analysis. Gynecologic and Obstetric Investigation, 86(3), 218–230. https://doi.org/10.1159/000515893

Weiner, M. R., Gurevich, P., Shinwell, E. S., & Yogev, Y. (2024). Pregnancy Complicated by Diabetes Mellitus. In Richard J. MartinAvroy A. Fanaroff (Ed.), Fanaroff and Martin’s Neonatal-Perinatal Medicine (12th ed.). Elsevier.

Whalen, K. L., & Taylor, J. R. (2017). Gestational Diabetes Mellitus. In PSAP 2017 Book 1: Endocrinology/Nephrology (Vol. 1).

Yang, K. C. (2024). Infants of Diabetic Mothers. In Robert M. Kliegman, Joseph W. St. Geme, Nathan J. Blum, Robert C. Tasker, Karen M. WilsonAbigail M. Schuh, & Cara L. Mack (Eds.), Nelson Textbook of Pediatrics (22nd ed., pp. 1140–1143). Elsevier.

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