Metformin in gestational diabetes: physiological actions and clinical applications

Metformin is an effective oral hypoglycaemic agent used in the treatment of type 2 diabetes mellitus; however, its use in pregnancy for the treatment of gestational diabetes mellitus (GDM) remains controversial owing to concerns around safety and efficacy. This comprehensive review outlines the physiological metabolic functions of metformin and synthesizes existing literature and key knowledge gaps pertaining to the use of metformin in pregnancy across various end points in women with GDM. On the basis of current evidence, metformin reduces gestational weight gain, neonatal hypoglycaemia and macrosomia and increases insulin sensitivity. However, considerable heterogeneity between existing studies and the grouping of aggregate and often inharmonious data within meta-analyses has led to disparate findings regarding the efficacy of metformin in treating hyperglycaemia in GDM. Innovative analytical approaches with stratification by individual-level characteristics (for example, obesity, ethnicity, GDM severity and so on) and treatment regimens (diagnostic criteria, treatment timing and follow-up duration) are needed to establish efficacy across a range of end points and to identify which, if any, subgroups might benefit from metformin treatment during pregnancy. This Review outlines the complex actions of metformin in metabolic regulation, providing a plausible basis for its benefits in the management of gestational diabetes mellitus. The authors also critically evaluate the safety profile of metformin use during pregnancy in patients with gestational diabetes mellitus.