We prospectively assessed whether a metformin diet safely provided primary and secondary prevention of gestational diabetes (GD) in 142 nondiabetic women with polycystic ovary syndrome (PCOS) who had at least one livebirth pregnancy. Women with BMI < 25 kg/m2 or ≥ 25 kg/m2 were instructed in 2,000 or 1,500 calorie/d, respectively, high-protein (26%), low-carbohydrate (44%), low-fat (30%) diets, with P/S ratio = 2/1. Metformin, targeted to 2 to 2.55 g/d, was given preconception and through pregnancy. On metformin, GD developed in 12 of 171 (7.0%) pregnancies in the 142 women. Of the 142 women, 46 had 1 or more previous livebirth pregnancies (n = 62) without metformin, developing GD in 19 (30.6%). Subsequently, on metformin, these 46 women had 49 livebirth pregnancies, developing GD in 6 (12.2%), McNemar's S = 11.3, p = .0008. Fifteen women without metformin had 19 GD pregnancies. In their subsequent pregnancies on metformin, 10 of these 15 women had 11 pregnancies without GD and 5 of the 15 women had 5 pregnancies with GD. Metformin appears to protect against GD and, speculatively, later type 2 diabetes in PCOS, by reducing insulin resistance and protecting pancreatic beta cells' reserve during pregnancy, when both insulin resistance and insulin secretion are increased. Metformin during pregnancy in women with PCOS may provide primary and secondary prevention against GD.
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