Cardiometabolic outcomes in offspring of women treated with metformin versus insulin for gestational diabetes: A Systematic Review and meta-analysis

Introduction: Gestational diabetes mellitus (GDM) is commonly managed with either metformin or insulin, but their comparative effects on offspring cardiometabolic outcomes are not fully understood. Objective: To investigate the impact of metformin and insulin, two distinct pharmacological interventions, on cardiometabolic outcomes in offspring of mothers with GDM. Methodology: Systematic literature review was performed for articles (randomized control trials) published from 1974 to May 2024 using a predefined search strategy. Studies were screened for title and abstract followed by full text. Quality assessment was done using a separate risk of bias tool in line with the PRISMA-2020 checklist. Results: Among 5463 records, five studies (metformin = 409 children or insulin n = 434 children) were included. Offspring of metformin-treated mothers in the age range of 5-9 years had more fat-free mass (kg) by bioimpedance and abdominal (subcutaneous and visceral) fat volume (cm3) 3 ) by MRI. Fasting plasma glucose and triglycerides were lower in the metformin-treated group for offspring aged 5-9 years. No significant differences were observed for other cardiometabolic outcomes. Limited data available for offsprings less than 5 years of age precluded meta-analysis for the available outcomes, except for body weight, and difference for this was also not significant. Conclusion: In short term no major differences has been seen in most of the cardiometabolic outcomes evaluated in the meta-analysis. Future trials with longer follow up are required and in different ethnicities. Systematic review registration: PROSPERO-CRD42023450990.