Pharmacological management of gestational diabetes

Abstract

Recent studies indicate that metformin achieves glycemic control comparable to insulin and is associated with lower weight gain and a reduced risk of maternal hypoglycemia; however, it presents a greater need for insulin rescue. Nevertheless, metformin may be associated with higher therapeutic failure rates requiring rescue insulin. Glyburide presents the least favorable risk–benefit profile, potentially being associated with worse neonatal outcomes, such as hypoglycemia and macrosomia, compared with metformin or insulin. Objective: To synthesize current evidence on the comparative efficacy and safety of insulin, metformin, and glyburide in the management of Gestational Diabetes Mellitus (GDM). Methods: A systematic search was conducted in databases (PubMed/PMC, ScienceDirect, MDPI) to identify recent systematic reviews, meta-analyses, and randomized controlled trials (2018–2025). Study selection was guided by PICO criteria and followed PRISMA methodology. Maternal outcomes (glycemic control, weight gain, hypoglycemia) and neonatal outcomes (macrosomia, neonatal hypoglycemia, neonatal intensive care unit admission) were evaluated. Results: 11 studies that met the search criteria were included. According to the findings obtained, the systematic review provided a more detailed overview of the evidence. Recent data confirm the efficacy and safety of pharmacological treatment in gestational diabetes, highlighting primarily the use of metformin as a valid alternative to insulin due to its good adherence and lower cost. Insulin remains the reference treatment, especially in cases with poor glycemic control. In contrast, glyburide shows a higher maternal and neonatal risk. Long-term research is required to assess the metabolic effects on offspring exposed to metformin during pregnancy. Conclusion: Metformin emerges as an effective, short-term safe, and patient-preferred option, representing a first-line alternative to standard insulin therapy.