Comparison of the Effect of Insulin with Metformin on Neonatal Outcome in Booked Patients with Gestational Diabetes Mellitus: Insulin vs Metformin in GDM: Neonatal Outcomes

Maria Ishtiaque; Mahham Janjua; Nomia Ashraf; Saima Choudhary; Tayyaba Iqbal; Naheed Akhtar

doi:10.54393/pjhs.v7i7.2956

Authors

Maria Ishtiaque Department of Obstetrics and Gynaecology, King Edward Medical University, Lahore, Pakistan
Mahham Janjua Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University, Sir Ganga Ram Hospital, Lahore, Pakistan
Nomia Ashraf Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University, Sir Ganga Ram Hospital, Lahore, Pakistan
Saima Choudhary Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University, Sir Ganga Ram Hospital, Lahore, Pakistan
Tayyaba Iqbal Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University, Sir Ganga Ram Hospital, Lahore, Pakistan
Naheed Akhtar Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University, Sir Ganga Ram Hospital, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v7i7.2956

Keywords:

Metformin, Gestational Diabetes Mellitus, Insulin, Macrosomia, Jaundice, Respiratory Distress

Abstract

Insulin has long been used as a treatment for gestational diabetes that is not well managed with diet. Metformin has been shown in several trials conducted in recent years to produce perinatal and obstetric results that are comparable to those of insulin. Studies have reported conflicting results regarding both modalities, and not all clinical recommendations support its usage. Objective: To compare neonatal outcomes in patients with metformin-treated gestational diabetes mellitus versus those with insulin-treated gestational diabetes mellitus. Methods: An observational study took place at the Obstetrics and Gynaecology Unit-III of Lady Willingdon Hospital, Lahore, during the time period starting from January 1, 2023, until December 1, 2023. One hundred and eighty-eight patients (94 in each group) were included in the study. In Group A, metformin tablets were given, and patients in Group B were given insulin. Outcome variables were measured as per the operational definition, respectively. Results: Patients receiving insulin therapy developed macrosomia more frequently (10.6% in the Metformin group vs. 23.4% in the Insulin group, p=0.029), along with hypoglycaemia (19.2% for Metformin vs. 33% for Insulin, p=0.031) and respiratory distress (9.6% Metformin vs. 20.2% Insulin, p=0.041) statistically often. Research showed no meaningful differences in findings between study groups regarding jaundice occurrence, together with intrauterine growth restriction (IUGR) and amniotic fluid measurements. Conclusions: In comparison to insulin, metformin is equally effective in preventing neonatal complications such as macrosomia, hypoglycaemia, and respiratory distress in women with gestational diabetes.

References

Lowe J, Ostrow B, Derkenne R, France N, Nandalall L, Pak J et al. Adaptation of the IDF WINGS Program for Hyperglycaemia in Pregnancy in Guyana, South America. Authorea Preprints. 2020 May. doi: 10.22541/au.158938526.61858862. DOI: https://doi.org/10.22541/au.158938526.61858862

Sheng B, Ni J, Lv B, Jiang G, Lin X, Li H. Short-Term Neonatal Outcomes in Women with Gestational Diabetes Treated Using Metformin Versus Insulin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Acta Diabetologica. 2023 May; 60(5): 595-608. doi: 10.1007/s00592-022-02016-5. DOI: https://doi.org/10.1007/s00592-022-02016-5

Dipla K, Zafeiridis A, Mintziori G, Boutou AK, Goulis DG, Hackney AC. Exercise as a Therapeutic Intervention in Gestational Diabetes Mellitus. Endocrines. 2021 Mar; 2(2): 65-78. doi: 10.3390/endocrines2020007. DOI: https://doi.org/10.3390/endocrines2020007

Amin F, Usman S, Choudhry A, Baloch SA, Aslam QU. Comparison of Fetal Outcome in Patients with Gestational Diabetes Treated with Metformin and Insulin. Pakistan Armed Forces Medical Journal. 2022 May; 72. doi: 10.51253/pafmj.v72iSUPPL-2.3872. DOI: https://doi.org/10.51253/pafmj.v72iSUPPL-2.3872

Ogurtsova K, Guariguata L, Barengo NC, Ruiz PL, Sacre JW, Karuranga S et al. International Diabetes Federation Diabetes Atlas: Global Estimates of Undiagnosed Diabetes in Adults for 2021. Diabetes Research and Clinical Practice. 2022 Jan; 183: 109118. doi: 10.1016/j.diabres.2021.109118. DOI: https://doi.org/10.1016/j.diabres.2021.109118

Riaz M, Nawaz A, Masood SN, Fawwad A, Basit A, Shera A. Frequency of Gestational Diabetes Mellitus Using DIPSI Criteria, A Study from Pakistan. Clinical Epidemiology and Global Health. 2019; 7(2): 218-221. doi: 10.1016/j.cegh.2018.06.003. DOI: https://doi.org/10.1016/j.cegh.2018.06.003

Cernea S, Dima L, Correll CU, Manu P. Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics. Drugs. 2020 Nov; 80(17): 1763-81. doi: 10.1007/s40265-020-01393-x. DOI: https://doi.org/10.1007/s40265-020-01393-x

Egan AM, Dow ML, Vella A. A Review of the Pathophysiology and Management of Diabetes in Pregnancy. Mayo Clinic Proceedings. 2020; 95(12): 2734-2746. doi: 10.1016/j.mayocp.2020.02.019. DOI: https://doi.org/10.1016/j.mayocp.2020.02.019

Musa OA, Syed A, Mohamed AM, Chivese T, Clark J, Furuya-Kanamori L et al. Metformin is Comparable to Insulin for Pharmacotherapy in Gestational Diabetes Mellitus: A Network Meta-Analysis Evaluating 6046 Women. Pharmacol Research. 2021 May; 167: 105546. doi: 10.1016/j.phrs.2021.105546. DOI: https://doi.org/10.1016/j.phrs.2021.105546

Wu Y, Tu M, Huang Y, Liu Y, Zhang D. Association of Metformin with Pregnancy Outcomes in Women with Polycystic Ovarian Syndrome Undergoing In vitro Fertilization: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2020; 3(8): 1-12. doi: 10.1001/jamanetworkopen.2020.11995. DOI: https://doi.org/10.1001/jamanetworkopen.2020.11995

Kurosawa K, Chiba K, Noguchi S, Nishimura T, Tomi M. Development of a Pharmacokinetic Model of Transplacental Transfer of Metformin to Predict In Vivo Fetal Exposure. Drug Metabolism and Disposition: The Biological Fate of Chemicals. 2020; 48(12): 1293-1302. doi: 10.1124/dmd.120.000127. DOI: https://doi.org/10.1124/dmd.120.000127

LaMoia TE and Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocrine Reviews. 2021 Feb; 42(1): 77-96. doi: 10.1210/endrev/bnaa023. DOI: https://doi.org/10.1210/endrev/bnaa023

Biondo LA, Teixeira AA, de OS Ferreira KC, Neto JC. Pharmacological Strategies for Insulin Sensitivity in Obesity and Cancer: Thiazolidinediones and Metformin. Current Pharmaceutical Design. 2020 Mar; 26(9): 932-945. doi: 10.2174/1381612826666200122124116. DOI: https://doi.org/10.2174/1381612826666200122124116

Bacon S, Burger D, Tailor M, Sanchez JJ, Tomlinson G, Murphy HR et al. Can Placental Growth Factors Explain Birthweight Variation in Offspring of Women with Type 1 Diabetes? Diabetologia. 2021 Jul; 64: 1527-1535. doi: 10.1007/s00125-021-05438-y. DOI: https://doi.org/10.1007/s00125-021-05438-y

Paavilainen E, Tertti K, Nikkinen H, Veijola R, Vääräsmäki M, Loo BM et al. Metformin Versus Insulin Therapy for Gestational Diabetes: Effects on Offspring Anthropometrics and Metabolism at the Age of 9 Years: A Follow‐Up Study of Two Open‐Label, Randomized Controlled Trials. Diabetes, Obesity, and Metabolism. 2022 Mar; 24(3): 402-410. doi: 10.1111/dom.14589. DOI: https://doi.org/10.1111/dom.14589

Akinyemi OA, Omokhodion OV, Fasokun ME, Makanjuola D, Ade-Ojo IP, Adeniyi AA et al. Screening for Gestational Diabetes Mellitus: Is There a Need for Early Screening for All Women in Developing Countries? Cureus. 2023 Feb; 15(2): 1-7. doi: 10.7759/cureus.35533 DOI: https://doi.org/10.7759/cureus.35533

Wang W, Fan Y, Lin Q. Metformin Combined with Insulin Aspart for Ameliorating Blood Glucose Levels and Maternal and Neonatal Outcomes in Women with Gestational Diabetes Mellitus and Chronic Hypertension. American Journal of Translational Research. 2021; 13(5): 5596.

Elsaeed UA, Riad RI, Taher A, Elnokeety M, Elanwary S. Pregnancy Outcomes in Pregnant Women with Diabetes Treated with Insulin Alone and Insulin with Metformin. Bali Medical Journal. 2022; 11(3): 1234-1242. doi: 10.15562/bmj.v11i3.3082. DOI: https://doi.org/10.15562/bmj.v11i3.3082

Simeonova-Krstevska S, Bogoev M, Bogoeva K, Zisovska E, Samardziski I, Velkoska-Nakova V et al. Maternal and Neonatal Outcomes in Pregnant Women with Gestational Diabetes Mellitus Treated with Diet, Metformin, or Insulin. Macedonian Journal of Medical Sciences. 2018; 6(5): 803. doi: 10.3889/oamjms.2018.200. DOI: https://doi.org/10.3889/oamjms.2018.200

Dunne F, Newman C, Alvarez-Iglesias A, Ferguson J, Smyth A, Browne M et al. Early Metformin in Gestational Diabetes: A Randomized Clinical Trial. Jama. 2023 Oct; 330(16): 1547-1556. doi: 10.1001/jama.2023.19869. DOI: https://doi.org/10.1001/jama.2023.19869

Dietsche KB, Magge SN, Dixon SA, Davis FS, Krenek A, Chowdhury A et al. Glycemia and Gluconeogenesis with Metformin and Liraglutide: A Randomized Trial in Youth-Onset Type 2 Diabetes. The Journal of Clinical Endocrinology and Metabolism. 2024 May; 109(5): 1361-1370. doi: 10.1210/clinem/dgad669. DOI: https://doi.org/10.1210/clinem/dgad669

Barroso E, Jurado-Aguilar J, Wahli W, Palomer X, Vázquez-Carrera M. Increased Hepatic Gluconeogenesis and Type 2 Diabetes Mellitus. Trends in Endocrinology and Metabolism. 2024 Dec; 35(12): 1062-1077. doi: 10.1016/j.tem.2024.05.006. DOI: https://doi.org/10.1016/j.tem.2024.05.006

Yang M, Wei Y, Liu J, Wang Y, Wang G. Contributions of Hepatic Insulin Resistance and Islet β-Cell Dysfunction to the Blood Glucose Spectrum in Newly Diagnosed Type 2 Diabetes Mellitus. Diabetes and Metabolism Journal. 2025; 49(4): 883-892. doi: 10.4093/dmj.2024.0537. DOI: https://doi.org/10.4093/dmj.2024.0537

Yang F, Liu H, Ding C. Gestational Diabetes Mellitus and Risk of Neonatal Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis. Diabetology Metabolic Syndrome. 2024 Dec; 16(1): 1-2. doi: 10.1186/s13098-024-01539-x. DOI: https://doi.org/10.1186/s13098-024-01539-x

Bailore V, Basany K, Banda M. Adverse Pregnancy Outcomes with Respect to Treatment Modalities in Women with Gestational Diabetes Mellitus at a Rural Tertiary Care Teaching Hospital. Journal of Family Medicine and Primary Care. 2024 Aug; 13(8): 2986-2992. doi: 10.4103/jfmpc.jfmpc_1495_23. DOI: https://doi.org/10.4103/jfmpc.jfmpc_1495_23

Garsia K, MacMillan F, Dune T, Simmons D. The Role of the Pharmacist in Contraception and Pre-Pregnancy Management for Women with Diabetes: A Study of Patient and Pharmacist Perspectives. Journal of Pharmaceutical Health Services Research. 2021 Sep; 12(3): 377-389. doi: 10.1093/jphsr/rmab019. DOI: https://doi.org/10.1093/jphsr/rmab019