Impact of metformin treatment during pregnancy on maternal outcomes: a systematic review/meta-analysis

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Tarry-Adkins, Jane L. 
Ozanne, Susan E. 
Aiken, Catherine E. 

Abstract: We systematically assessed the impact of metformin treatment on maternal pregnancy outcomes. PubMed, Ovid Embase, Medline, Web of Science, and Cochrane databases were systematically searched (inception-1st February 2021). Randomised controlled trials reporting pregnancy outcomes in women randomised to metformin versus any other treatment for any indication were included. Outcomes included gestational weight gain (GWG), pre-eclampsia, gestational hypertension, preterm birth, gestational age at delivery, caesarean section, gestational diabetes, glycaemic control, and gastrointestinal side-effects. Two independent reviewers conducted screening, with a third available to evaluate disagreements. Risk-of-bias and GRADE assessments were conducted using Cochrane Risk-of-Bias and GRADE-pro software. Thirty-five studies (n = 8033 pregnancies) met eligibility criteria. GWG was lower in pregnancies randomised to metformin versus other treatments (1.57 kg ± 0.60 kg; I2 = 86%, p < 0.0001), as was likelihood of pre-eclampsia (OR 0.69, 95% CI 0.50–0.95; I2 = 55%, p = 0.02). The risk of gastrointestinal side-effects was greater in metformin-exposed versus other treatment groups (OR 2.43, 95% CI 1.53–3.84; I2 = 76%, p = 0.0002). The risk of other maternal outcomes assessed was not significantly different between metformin-exposed versus other treatment groups. Metformin for any indication during pregnancy is associated with lower GWG and a modest reduced risk of pre-eclampsia, but increased gastrointestinal side-effects compared to other treatments.

Article, /692/699, /692/163, article
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Scientific Reports
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Nature Publishing Group UK
British Heart Foundation (RG/17/12/33167)
Medical Research Council (MC_UU_00014/4, MR/T016701/1)
Action Medical Research (GN2788)