Metformin versus insulin in glycemic control in pregnancy (MevIP): a randomized clinical trial protocol

Gestational diabetes is one of the most prevalent diseases in pregnancy, with an incidence of 5 to 18% in Brazil, and is associated with high morbidity rates. The first-line treatment is insulin, although some recent studies have indicated that metformin might also be effective. Metformin is safe in pregnancy and appears to produce better results than insulin, including reduced gestational weight gain (GWG) and smaller gestational-age newborns. Few studies have been conducted on this topic in low- and middle-income countries.

We designed an open randomized controlled trial comparing two treatments for pregnant women with type II diabetes mellitus (DM) and gestational diabetes (DMG): the metformin group (intervention) and the insulin group (as a routine service). The primary outcome is glycemic control. The secondary outcomes are GWG, the occurrence of hypertensive syndromes, macrosomia, and neonatal hypoglycemia. The sample will comprise 92 pregnant women, 46 per group. The inclusion criteria will be GDM or type II DM requiring medication for glycemic control, singleton pregnancy, and gestational age under 34 weeks. The exclusion criteria will be current treatment with any medication for glycemic control, type I DM, and intolerance to the study medications (metformin or insulin). Women will be routinely followed during antenatal care, childbirth, and the postpartum period. Statistical analyses will include the intention-to-treat approach and a comparison between the two groups.

Considering the Brazilian socioeconomic reality and the safety of metformin demonstrated in previous trials, we expect that the MevIP study will demonstrate that metformin is an adequate and appropriate medication for GDM treatment in the Brazilian population, representing an alternative to insulin for GDM.

This protocol has been registered prospectively in ReBEC under the ID RBR-3j3cktx in August 11, 2023.