Glueck, C. J., Wang, P., Kobayashi, S., Phillips, H., & Sieve-Smith, L. (2002). Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertility and Sterility, 77(3), 520-525. https://doi.org/10.1016/s0015-0282(01)03202-2
Glueck CJ, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril. 2002;77(3):520-525. doi:10.1016/s0015-0282(01)03202-2
Glueck, C. J., et al. "Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome." Fertility and Sterility, vol. 77, no. 3, 2002, pp. 520-525.
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Metformin was linked to far less gestational diabetes in PCOS
Among 72 women with PCOS who had live births, gestational diabetes arose in 3 out of 100 pregnancies with metformin and 31 out of 100 without it. The study followed one group forward and reviewed another backward. Adjusted for age, metformin was associated with about a tenfold lower rate in these women.
Key Findings
With metformin, 1 of 33 pregnancies (3%) involved gestational diabetes. Without it, the figure was 22 of 72 pregnancies (31%).
Among the 33 metformin women, 8 of 12 (67%) earlier pregnancies without the drug had involved gestational diabetes.
Age-adjusted odds ratios were 0.093 (95% CI: 0.011 to 0.795) comparing women and 0.115 (95% CI: 0.014 to 0.938) comparing pregnancies.
Among the 33 women taking metformin, none developed lactic acidosis, and their 34 live births included no major fetal malformations or fetal hypoglycemia.
Interpretation
The study pairs 33 women who conceived on metformin, followed forward in time, with 39 women whose earlier births came without it, reviewed backward. The women on metformin were told to follow a low-carbohydrate, high-protein diet, limited to 1500 calories a day before conception. The authors say the diet may have contributed to the lower rate. The women had no diabetes before pregnancy and met 1990 National Institutes of Health criteria for PCOS. The authors estimate a blinded placebo trial would need 102 live births.
RRM Context
PCOS, now also called PMOS (Polyendocrine Metabolic Ovarian Syndrome), often comes with insulin resistance, and the paper ties that to gestational diabetes. RRM looks for the cause early, before pregnancy.
Our editorial summary of this paper, not the article's abstract.
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.
Patients
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.
Interventions
Metformin, 2.55 g/d, throughout pregnancy in women with PCOS.
Main Outcome Measures
Development of gestational diabetes in women with PCOS.
Results
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).
Conclusions
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 beta-cells by insulin resistance and pregnancy.
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