Neonatal outcomes in gestational diabetes mellitus: metformin alone versus metformin with insulin: a retrospective cohort study in India

Dharshan G. B.; Rahul S. Rao; Vijaya Shambhavi B.; Shreya D. P.; Bharathi K. R.; Varsha I. Dalal

doi:10.18203/2320-1770.ijrcog20263417

Authors

Dharshan G. B. Department of Pharmacy Practice, PES Institute of Pharmacy, Bengaluru, Karnataka, India https://orcid.org/0009-0000-0598-481X
Rahul S. Rao Department of Pharmacy Practice, PES Institute of Pharmacy, Bengaluru, Karnataka, India https://orcid.org/0009-0002-8127-4320
Vijaya Shambhavi B. Department of Pharmacy Practice, PES Institute of Pharmacy, Bengaluru, Karnataka, India
Shreya D. P. Department of Pharmacy Practice, PES Institute of Pharmacy, Bengaluru, Karnataka, India
Bharathi K. R. Department of Obstetrics and Gynaecology, PESU Institute of Medical Sciences and Research, Bengaluru, Karnataka India
Varsha I. Dalal Department of Pharmacy Practice, PES Institute of Pharmacy, Bengaluru, Karnataka, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20263417

Keywords:

Metformin, Insulin, Gestational diabetes mellitus, Neonatal outcomes, NICU admission, Birth weight

Abstract

Background: Gestational diabetes mellitus (GDM) is associated with adverse neonatal outcomes, including increased neonatal intensive care unit (NICU) admissions and differences in birth weight. Although metformin is commonly used for glycemic control in GDM, some patients require adjunctive insulin therapy. Comparative data on neonatal outcomes between these regimens remain inadequate.

Methods: This retrospective cohort study was conducted at a tertiary care center in Bengaluru, India. Medical records of women with singleton GDM pregnancies were analyzed and categorized into two groups: metformin monotherapy and metformin plus insulin. Primary outcomes were NICU admission and neonatal birth weight. Logistic regression was utilized to determine predictors of NICU admission, and linear regression estimated determinants of birth weight.

Results: Among 123 GDM pregnancies, 52.8% received metformin alone and 47.2% received combination therapy. NICU admissions were significantly lower in the metformin group compared to the combination group (46.2% versus. 74.1%, p=0.002). After adjusting for gestational age, metformin monotherapy was associated with reduced odds of NICU admission (OR=0.41, p=0.032), though maternal HbA1C emerged as the strongest predictor (AUC=0.751). When both HbA1C and birth weight were included in the model, treatment regimen lost statistical significance (p=0.056). Neonatal birth weight was significantly lower in the combination group (mean difference -0.30 kg), with gestational age showing a stronger association (0.151 kg/week, p<0.001).

Conclusions: Although NICU admissions were lower in the metformin monotherapy group, maternal glycemic control particularly HbA1C appears to be the principal determinant of neonatal outcomes in GDM pregnancies.

Metrics

Metrics Loading ...

References

Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Investig. 2005;115(3):485-91. DOI: https://doi.org/10.1172/JCI200524531

Oskovi-Kaplan ZA, Ozgu-Erdinc AS. Management of gestational diabetes mellitus. Adv Exp Med Biol. 2021;1307:257-72. DOI: https://doi.org/10.1007/5584_2020_552

Farrar D. Hyperglycemia in pregnancy: prevalence, impact, and management challenges. Int J Womens Health. 2016;8:519-27. DOI: https://doi.org/10.2147/IJWH.S102117

Mittal R, Prasad K, Lemos JRN, Arevalo G, Hirani K. Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management. Int J Mol Sci. 2025;26(5):2320. DOI: https://doi.org/10.3390/ijms26052320

Bedell S, Hutson J, de Vrijer B, Eastabrook G. Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions. Curr Vasc Pharmacol. 2021;19(2):176-92. DOI: https://doi.org/10.2174/18756212MTA3qNDApy

Clarke E, Cade TJ, Brennecke S. Early Pregnancy Screening for Women at High-Risk of GDM Results in Reduced Neonatal Morbidity and Similar Maternal Outcomes to Routine Screening. J Pregnancy. 2020;2020:9083264. DOI: https://doi.org/10.1155/2020/9083264

Malaza N, Masete M, Adam S, Dias S, Nyawo T, Pheiffer C. A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes. Int J Environ Res Public Health. 2022;19(17):10846. DOI: https://doi.org/10.3390/ijerph191710846

Beta J, Khan N, Khalil A, Fiolna M, Ramadan G, Akolekar R. Maternal and neonatal complications of fetal macrosomia: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2019;54(3):308-18. DOI: https://doi.org/10.1002/uog.20279

Karcz K, Królak-Olejnik B. Impact of Gestational Diabetes Mellitus on Fetal Growth and Nutritional Status in Newborns. Nutrients. 2024;16(23):4093. DOI: https://doi.org/10.3390/nu16234093

Tsikouras P, Kotanidou S, Nikolettos K, Kritsotaki N, Bothou A, Andreou S, et al. Shoulder dystocia: a comprehensive literature review on diagnosis, prevention, complications, prognosis, and management. J Pers Med. 2024;14(6):586. DOI: https://doi.org/10.3390/jpm14060586

Preda A, Pădureanu V, Moța M, Ștefan AG, Comănescu AC, Radu L, et al. Analysis of maternal and neonatal complications in a group of patients with gestational diabetes mellitus. Medicina. 2021;57(11):1170. DOI: https://doi.org/10.3390/medicina57111170

Napoli A. Insulin therapy and diabetic pregnancy. Am. J. Ther. 2020;27(1):e91-105. DOI: https://doi.org/10.1097/MJT.0000000000001095

Gray SG, McGuire TM, Cohen N, Little PJ. The emerging role of metformin in gestational diabetes mellitus. Diabetes Obes. Metab. 2017;19(6):765-72. DOI: https://doi.org/10.1111/dom.12893

Nguyen L, Chan SY, Teo AK. Metformin from mother to unborn child–are there unwarranted effects? EBioMedicine. 2018;35:394-404. DOI: https://doi.org/10.1016/j.ebiom.2018.08.047

NICE. Recommendations. Diabetes in pregnancy: management from preconception to the postnatal period. 2015. Available at: https://www.nice.org.uk/ guidance/ng3/chapter/recommendations. Accessed on 15 May 2026.

Picón-César MJ, Molina-Vega M, Suárez-Arana M, González-Mesa E, Sola-Moyano AP, Roldan-López R, et al. Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial. Am J Obstet Gynecol. 2021;225(5):517. DOI: https://doi.org/10.1016/j.ajog.2021.04.229

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 Diabetol. 2023;60(5):595-608. DOI: https://doi.org/10.1007/s00592-022-02016-5

Al-Shahrani AM. Predictors of Neonatal Intensive Care Unit Admission and Adverse Outcomes Related to Gestational Diabetes. Cureus. 2023;15(5):e38579. DOI: https://doi.org/10.7759/cureus.38579

American Diabetes Association Professional Practice Committee. 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1):S306-20. DOI: https://doi.org/10.2337/dc25-S015

World Health Organization. WHO recommendations on care for women with diabetes during pregnancy. 2025. Available at: https://www.who.int/publica tions/i/item/9789240117044. Accessed on 15 May 2026.