Optimizing diabetes care in pregnancy: A systematic review of glycemic targets, treatment initiation, and glucose-lowering pharmacological management for T1DM, T2DM, and GDM.

Introduction: Pregnant women with diabetes are at increased risk of adverse maternal and neonatal outcomes, yet the optimal approach to achieving recommended glucose levels and glucose-lowering pharmacological strategies during pregnancy remains unclear. Methods: We conducted a systematic review with meta-analysis of randomized controlled trials (RCTs) synthesizing the evidence on glycemic targets and pharmacological interventions for pregnant women with pre-existing diabetes or gestational diabetes mellitus (GDM). We extracted data for outcomes prioritized for the development of all WHO guidelines on maternal and perinatal health, as well as intervention-specific outcomes. The selected critical outcomes were maternal death, maternal functioning and women's views and experiences, stillbirth/fetal death, neonatal death, and perinatal death. We followed standard Cochrane methods. Results: The evidence on glycemic targets was very limited. Among women with type 1 diabetes mellitus (T1DM), meeting stricter glycemic targets may increase the risk of hypoglycemia and longer hospitalization, whereas less stringent targets may increase the risk of caesarean birth, large-for-gestational-age babies, and neonatal respiratory distress syndrome. In women with GDM, no clear differences were observed between a tight and moderate target. Evidence on the optimal approach to glucose-lowering pharmacotherapy for the management of type 1 and type 2 diabetes during pregnancy was also limited. In women with GDM, metformin was associated with better maternal and neonatal outcomes than glibenclamide. Compared to insulin, metformin probably reduces the risk of neonatal intensive care admission and neonatal hypoglycemia. We rated most outcomes as low or very low certainty, which means that the true effects of the interventions may differ substantially from current estimates, and new evidence is likely to change our confidence in the estimates of effects. The main reasons for downgrading the certainty of the evidence were risk of bias and imprecision. Conclusions: This review did not yield sufficient evidence to determine which glycemic targets are the most effective in improving health outcomes in women with pre-existing diabetes or GDM. Current evidence on glucose-lowering pharmacotherapy in pregnancy is limited and generally of low certainty. In women with GDM, metformin and insulin appeared to offer benefits compared to glibenclamide, and metformin may be a safe first-line alternative to insulin, although the evidence is limited for most outcomes. High-quality RCTs are needed to clarify the effects of these interventions, including into the longer term for the child. PROSPERO registration: CRD42025630036.