Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome

Abstract Objective: To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome (PCOS). Design: Prospective and retrospective study. Setting: Outpatient clinical research center. Patient(s): The prospective study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births; of these, 28 were taking metformin through delivery. The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy. Intervention(s): Metformin, 2.55 g/d, throughout pregnancy in women with PCOS. Main Outcome Measure(s): Development of gestational diabetes in women with PCOS. Result(s): Before metformin therapy, after covariance adjustment for age, the two cohorts did not differ in height, weight, basal metabolic index, insulin, insulin resistance, or insulin secretion. Both cohorts had high fasting insulin, were insulin resistant, and had high insulin secretion. Among the 33 women who received metformin, gestational diabetes developed in 1 of 33 (3%) pregnancies versus 8 of 12 (67%) of their previous pregnancies without metformin. Among the 39 women who did not take metformin, gestational diabetes developed in 14 of 60 (23%) pregnancies. When all live births were combined, gestational diabetes occurred in 22 of 72 pregnancies (31%) in women who did not take metformin versus 1 of 33 pregnancies (3%) in those who took metformin. With gestational diabetes as the response variable and age at delivery and treatment group (metformin or no metformin) as explanatory variables, the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 (95% CI: 0.011 to 0.795). With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group (metformin no metformin) as explanatory variables, the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 (95% CI: 0.014 to 0.938). Conclusion(s): In PCOS, use of metformin is associated with a 10-fold reduction in gestational diabetes (31% to 3%). It also reduces insulin resistance and insulin secretion, thus decreasing the secretory demands imposed on pancreatic β-cells by insulin resistance and pregnancy.