Management of pregnancy with metformin: Case reports for genetic insulin resistance syndrome and a literature review for gestational and type 2 diabetes.

Introduction: Genetic insulin resistance syndrome is characterized by severe insulin resistance due to functional abnormalities of the insulin receptor or downstream signaling molecules. Treatment typically includes insulin formulations and oral hypoglycemic agents such as metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, achieving adequate glycemic control remains challenging. Moreover, given its rarity, reports on perinatal glycemic management in affected pregnancies remain scarce.

Materials and methods: We describe prenatal care for two cases of genetic insulin resistance syndrome: a case of type A insulin resistance syndrome attributed to a heterozygous variant (Asn462Ser) of INSR (case 1) and a case of genetic insulin resistance syndrome due to a heterozygous variant (Arg649Trp) of PIK3R1 (case 2). We also review the literature for metformin treatment of gestational diabetes mellitus (GDM) or type 2 diabetes during pregnancy.

Results: In case 1, perinatal glycemic management during three pregnancies was achieved with metformin alone, resulting in deliveries without any adverse events for both mother and infants. In case 2, administration of metformin during pregnancy initially reduced daily insulin requirements from 230 to 50 U/day, with a predelivery insulin dose of 112 U/day. At 34 weeks of gestation, a cesarean section was performed because of intractable uterine contractions. The child was diagnosed as small for gestational age and harbored the same genetic variant as the mother.

Conclusions: The present cases suggest that metformin administration during pregnancy can be beneficial in cases of genetic insulin resistance syndrome, similar to its use in pregnancies associated with T2D or GDM.