American Diabetes Association
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Determinants of Small for Gestational Age in Women with Type 2 Diabetes in Pregnancy: Who should get Metformin?

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posted on 2022-06-07, 15:14 authored by Denice S Feig, Bernard Zinman, Elizabeth Asztalos, Lois E Donovan, Prakesh S Shah, J Johanna Sanchez, George Tomlinson, Kellie E Murphy, the MiTy Collaborative Group


In the MiTy [Metformin in Women with Type 2 Diabetes in Pregnancy] randomized trial of metformin vs placebo added to insulin, we found numerous benefits with metformin but identified an increased proportion of small for gestational age (SGA) infants. We aimed to determine the predictors of SGA in order to individualize care.


Using logistic regression, we assessed baseline maternal characteristics as predictors of SGA. We compared maternal/neonatal outcomes in SGA metformin and placebo groups using t-tests, chi-squared tests or Fisher’s exact tests, as appropriate.  


Of the 502 mothers, 460 infants were eligible for this study. There were 30 infants with SGA in the metformin group (12.9%) and 15 in the placebo group (6.6%) (p=0.026). Among SGA infants, those in the metformin group delivered significantly later than those in the placebo group (37.2 vs 35.3 weeks, p=0.038). In adjusted analyses, the presence of a comorbidity (chronic hypertension and/or nephropathy, OR 3.05 (95%CI1.58-5.81) and metformin use (OR 2.26 (95%CI1.19 to 4.74)) were predictive of SGA. The absolute risk of SGA was much higher in women on metformin with comorbidity compared to women on metformin without comorbidity (25.0% vs 9.8%).


In this study we observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin. Thus, with the aim of reducing SGA, it is reasonable to be cautious in our use of metformin in those with T2D and chronic hypertension or nephropathy in pregnancy.


Funding was received from Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto Department of Medicine.