Postpartum GLP-1 receptor agonists and SGLT-2 therapies in women with prior gestational diabetes: current evidence and uncertainties

Abstract

Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies and is associated with adverse pregnancy outcomes and a substantially increased risk of long-term cardiometabolic disease. Although glucose levels often normalise postpartum, women with prior GDM have a ten-fold increased risk of developing type 2 diabetes mellitus (T2DM), particularly when early postpartum prediabetes is present. Current prevention strategies, including lifestyle modification and metformin, have in general shown limited effectiveness in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve glycaemic control, promote weight loss, and reduce cardiovascular risk in people with T2DM and/or obesity. Given the central role of insulin resistance and weight retention in progression from GDM to T2DM, these therapies represent a promising strategy for postpartum diabetes prevention. However, available evidence in women with prior GDM is limited and largely derived from small, short-term studies not adequately powered to assess sustained diabetes prevention or long-term outcomes. Whether GLP-1 RA therapy should be considered an early preventive strategy in this high risk population remains therefore uncertain. The evidence base is now evolving, with the first large multicentre randomised controlled trial (RCT) with a potent GLP-1 RA in women with early postpartum prediabetes following GDM currently underway. In parallel, sodium–glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated robust cardiovascular and renal benefits in T2DM, independent of glycaemic status, and may offer additional preventive potential. Their insulin-independent mechanism and favourable cardiovascular profile are particularly attractive in women with prior GDM, who face elevated long-term cardiometabolic risk. However, uncertainties persist regarding safety in women of reproductive age, use during lactation, optimal timing, and patient selection, highlighting the gap between therapeutic promise and dedicated postpartum trial data. This Debate examines the emerging role of GLP-1 RA and SGLT-2 inhibitors in preventing T2DM after GDM. Despite their potential, important uncertainties remain regarding long-term efficacy and safety. While these therapies may provide a shift beyond lifestyle intervention and metformin, robust trial data and careful consideration of reproductive factors are required before routine implementation. We discuss how pharmacological prevention strategies could be integrated into postpartum care for this high-risk population.