Could there be a role for metformin in type 1 and type 2 diabetic pregnancies?

Pernicova, Ida; Prasai, Madhu Janina; Close, E.J.; Drury, K.C.; Gilbey, S. G.; Brewster, Jennifer; Scott, Eleanor M.

doi:10.1007/s00125-011-2256-8

Cited by 4 publications

(4 citation statements)

References 8 publications

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“…Metformin is approved for use in the treatment of GDM in many countries across the world and is featured in the 20th World Health Organization (WHO) essential medicines list [18], and it has been recommended by the Society for Maternal–Fetal Medicine (SMFM) as a first line treatment for GDM [19]. Available evidence suggests that metformin is effective in maintaining maternal glycaemic control and may help to limit gestational weight gain ([20] and reviewed in [21]). However, unlike insulin, metformin crosses the placenta and is present at clinically relevant concentrations in fetal and placental tissues (50%–100% of maternal concentrations) [22,23].…”

Section: Introductionmentioning

confidence: 99%

Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis

2019

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Background Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown. Methods and findings PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and the Cochrane database were systematically searched (from database inception to 26 February 2019). Outcomes of GDM-affected pregnancies randomised to treatment with metformin versus insulin were included (randomised controlled trials and prospective randomised controlled studies) from cohorts including European, American, Asian, Australian, and African women. Studies including pregnant women with pre-existing diabetes or non-diabetic women were excluded, as were trials comparing metformin treatment with oral glucose-lowering agents other than insulin. Two reviewers independently assessed articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Outcome measures were parameters of fetal, infant, and childhood growth, including weight, height, BMI, and body composition. In total, 28 studies ( n = 3,976 participants) met eligibility criteria and were included in the meta-analysis. No studies reported fetal growth parameters; 19 studies ( n = 3,723 neonates) reported measures of neonatal growth. Neonates born to metformin-treated mothers had lower birth weights (mean difference −107.7 g, 95% CI −182.3 to −32.7, I 2 = 83%, p = 0.005) and lower ponderal indices (mean difference −0.13 kg/m 3 , 95% CI −0.26 to 0.00, I 2 = 0%, p = 0.04) than neonates of insulin-treated mothers. The odds of macrosomia (odds ratio [OR] 0.59, 95% CI 0.46 to 0.77, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99, p = 0.04) were lower following maternal treatment with metformin compared to insulin. There was no difference in neonatal height or incidence of small for gestational age between groups. Two studies ( n = 411 infants) reported measures of infant growth (18–24 months of age). In contrast to the neonatal phase, metformin-exposed infants were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830, I 2 = 4%, p = 0.03). Three studies ( n = 520 children) reported mid-childhood growth parameters (5–9 years). In mid-childhood, BMI was significantly higher (mean difference 0.78 kg/m 2 , 95% CI 0.23 to 1.33, I 2 = 7%, p = 0.005) followin...

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Section: Introductionmentioning

confidence: 99%

Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis

2019

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“…Metformin is a biguanide that is commonly used as a first‐line therapy in the management of T2DM. Available data suggest that metformin is effective in improving maternal glycaemic control and may help to limit gestational weight gain 12,13 . However, metformin can cross the placenta and may affect foetal physiology directly, so potential safety concerns exist 14,15 .…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of metformin alone or as an add‐on therapy to insulin in pregnancy with GDM or T2DM: A systematic review and meta‐analysis of 21 randomized controlled trials

Guo

et al. 2021

Clinical Pharmacy Therapeu

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What is known and objective: Pregnant women are increasingly being exposed to metformin for conditions including gestational diabetes mellitus and type 2 diabetes mellitus. Metformin has been found to exhibit maternal to foetal transfer, and the long‐term influence is uncertain. We conducted a meta‐analysis to compare the efficacy and safety of metformin alone or as add‐on therapy to insulin and insulin in pregnancy with gestational diabetes mellitus or type 2 diabetes mellitus. Methods: We performed a comprehensive literature search of PubMed, Embase, Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) that compared metformin to insulin in pregnancy. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were used to synthesize the results. Two authors independently extracted the data, evaluated study quality and calculated pooled estimates. Results: Twenty‐one studies involving 4,545 patients were included in this meta‐analysis. Compared with insulin, metformin significantly reduced the risks of maternal weight gain [MD −1.51 kg, 95%CI (−1.90 kg, −1.12 kg), P < 0.00001], gestational age at birth [MD −0.12 week, 95%CI (−0.21 week, −0.02 week), P = 0.02], gestational hypertension [RR 0.63, 95%CI (0.48, 0.82), P = 0.0006], maternal hypoglycaemia [RR 0.33, 95%CI (0.15, 0.73), P = 0.006], birthweight [MD −0.13 kg, 95%CI (−0.20 kg, −0.07 kg), P < 0.0001], neonatal hypoglycaemia [RR 0.56, 95%CI (0.49, 0.64), P < 0.00001], neonatal intensive care unit admission [RR 0.73, 95%CI (0.64, 0.83), P < 0.00001], birthweight ≥4000 g [RR 0.70, 95%CI (0.59, 0.83), P < 0.0001], and large for gestational age [RR 0.83, 95%CI (0.72, 0.97), P = 0.02] and significantly increased the risk of small for gestational age [RR 1.43, 95%CI (1.08, 1.89), P = 0.01] in pregnancy. What is new and conclusion: Metformin may have potential benefits for pregnant women and newborns in terms of maternal and foetal outcomes. More studies with long‐term follow‐up of offspring exposed to metformin in utero are needed to provide evidence for the future use of metformin in pregnancy.

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“…We used a predefined data extraction table to perform data extraction, and publication bias measurement for each study will be accomplished through the Cochrane Collaboration Tool. The statistical analyses will be performed using RevMan (5.4.1; The Cochrane Collaboration) and STATA (17). Heterogeneity will be assessed using the Q and I² test, with a value of I² > 50% being considered substantial.…”

Section: Methods and Analysismentioning

confidence: 99%

“…16 Considerable evidence indicates that metformin efficiently stabilises maternal glycaemic control and might be conducive to curbing gestational weight gain. 17 Nevertheless, there are latent safety concerns that metformin can go through the placenta, which might directly influence fetal physiology homeosis. 18-19 Other studies of women with GDM have found elevated risks of small for gestational age (SGA) and premature delivery.…”

Section: Introductionmentioning

confidence: 99%

Effects of metformin use in pregnant women on maternal and infant outcomes: protocol for a systematic review and meta-analysis

Wang

pan

Wang

2022

Preprint

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Introduction Metformin has been considered for use in women who are overweight or obese and with pre-existing type 2 diabetes(T2DM) or gestational diabetes mellitus(GDM). Nevertheless, few studies have weighed the pros and cons of maternal metformin use on offspring and womens perinatal health. We determined to ascertain whether the insulin sensitiser metformin improves fetal and maternal outcomes in Pregnant women with type 2 diabetes or with a BMI no less than 24 kg/m2 Methods and analysis The protocol was formulated according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Exhaustive literature searches of electronic bibliographic databases will be conducted in PubMed, EMBASE, Cochrane Library, Web of Sciences, Scopus, ClinicalTrial, OvidSP and ScienceDirect. We used a predefined data extraction table to perform data extraction, and publication bias measurement for each study will be accomplished through the Cochrane Collaboration Tool. The statistical analyses will be performed using RevMan (5.4.1; The Cochrane Collaboration) and STATA (17). Heterogeneity will be assessed using the Q and I2 test, with a value of I2 > 50% being considered substantial. The extent of publication bias will be investigated by visual assessment of a funnel plot and using Eggers test, Beggs test, and Harbords test if ten or more trials are pooled. Ethics and dissemination Patients consent and Ethical approval are not requisites. The complete analysis will be published in an international open-access journal and translational articles to disseminate the results to clinical internists. PROSPERO registration number: CRD42022347084

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Could there be a role for metformin in type 1 and type 2 diabetic pregnancies?

Cited by 4 publications

References 8 publications

Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis

Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis

The efficacy and safety of metformin alone or as an add‐on therapy to insulin in pregnancy with GDM or T2DM: A systematic review and meta‐analysis of 21 randomized controlled trials

Effects of metformin use in pregnant women on maternal and infant outcomes: protocol for a systematic review and meta-analysis

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