Metformin versus insulin in gestational diabetes mellitus: a meta-analysis of randomized clinical trials

Zhu, Bin; Zhang, Limei; Fan, Yu; Wang, L.; Li, X. G.; Liu, T.; Cao, Yujia; Zhao, Zhigang

doi:10.1007/s11845-016-1414-x

Cited by 26 publications

(30 citation statements)

References 33 publications

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“…This necessitates careful dosage adjustment as pregnancy progresses. There is a risk of metformin accumulation in the neonate prior to birth, through recycling of amniotic fluid …”

Section: Metformin In Pregnancy: Translation Of Pharmacology To Practicementioning

confidence: 99%

The emerging role of metformin in gestational diabetes mellitus

Gray

McGuire

Cohen

et al. 2017

Diabetes Obesity Metabolism

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Metformin use during pregnancy is controversial and there is disparity in the acceptance of metformin treatment in women with gestational diabetes mellitus (GDM) in Australia. Despite short term maternal and neonatal safety measures, the placental transfer of metformin during GDM treatment and the absence of long-term safety data in offspring has regulators and prescribers cautious about its use. To determine the current role in GDM management, this literature review describes the physiological changes that occur in GDM and other forms of diabetes in pregnancy (DIP) and international changes in guidelines for GDM diagnosis. Management options are considered, with a focus on the evolving evidence for metformin, its mechanism of action, the maternal, foetal and neonatal outcomes associated with its use and benefit vs risk when compared with the current gold standard, insulin. Investigation reveals a favourable balance of evidence to support the safety and long-term benefits, to mother and child, of using metformin as an alternate to insulin for treatment of GDM. Recent findings of the gastrointestinal-directed action of metformin are at least as important as the hepatic effect and the availability of a novel delayed-release metformin dose form to exploit this new information provides a product and therapeutic strategy ideally suited to the use of metformin in GDM.

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“…This necessitates careful dosage adjustment as pregnancy progresses. There is a risk of metformin accumulation in the neonate prior to birth, through recycling of amniotic fluid …”

Section: Metformin In Pregnancy: Translation Of Pharmacology To Practicementioning

confidence: 99%

The emerging role of metformin in gestational diabetes mellitus

Gray

McGuire

Cohen

et al. 2017

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

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“…[13][14][15][16][17][18][19] Several studies have shown fewer BMI changes among obese women with GDM treated with this drug. [20][21][22] The results of the present study identified that participants in both control and metformin groups showed no significant increase in BMI between gestational weeks 20 and 24-28. The combination of metformin with lifestyle changes represents a potentially effective and safe approach to obesity control.…”

Section: Discussionmentioning

confidence: 84%

Effectiveness of Metformin in the Prevention of Gestational Diabetes Mellitus in Obese Pregnant Women

Sales

Nascimento

Dienstmann

et al. 2018

Rev Bras Ginecol Obstet

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“…Similarly, treatment of GDM with metformin has recently increased in Norway, Wales, and the rest of the UK [50]. Evidence from randomized controlled trials and observational studies revealing no adverse maternal or fetal/neonatal effects in the short-term [51, 52] supports using metformin for GDM [18]. The 2013 MiG trial comparing insulin vs. metformin for treating gestational diabetics confirmed the safety of metformin in pregnancy and revealed no differences in either maternal circulating hormones/metabolites, birth weight, or neonatal anthropometric measurements between the two treatments [53].…”

Section: Discussionmentioning

confidence: 99%

The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism

et al. 2016

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BackgroundMaternal obesity may program the fetus and increase the susceptibility of the offspring to adult diseases. Metformin crosses the placenta and has been associated with decreased inflammation and reversal of fatty liver in obese leptin-deficient mice. We investigated the effects of metformin on maternal and fetal lipid metabolism and hepatic inflammation using a rat model of diet-induced obesity during pregnancy.MethodsFemale Wistar rats (6–7 weeks old) were fed normal or high calorie diets for 5 weeks. After mating with normal-diet fed males, half of the high calorie-fed dams received metformin (300 mg/kg, daily); dams (8 per group) continued diets through gestational day 19. Maternal and fetal livers and fetal brains were analyzed for fatty acids and for fatty acid metabolism-related gene expression. Data were analyzed by ANOVA followed by Dunnett’s post hoc testing.ResultsWhen compared to control-lean maternal livers, obesogenic-diet-exposed maternal livers showed significantly higher saturated fatty acids (14:0 and 16:0) and monounsaturated fatty acids (16:1n7 and 18:1n9) and lower polyunsaturated (18:2n6 and 20:4n6 [arachidonic acid]) and anti-inflammatory n3 polyunsaturated fatty acids (18:3n3 and 22:6n3 [docosahexaenoic acid]) (p < 0.05). Metformin did not affect diet-induced changes in maternal livers. Fetal livers exposed to the high calorie diet showed significantly increased saturated fatty acids (18:0) and monounsaturated fatty acids (18:1n9 and 18:1n7) and decreased polyunsaturated fatty acids (18:2n6, 20:4n6 and 22:6n3) and anti-inflammatory n3 polyunsaturated fatty acids, along with increased gene expression of fatty acid metabolism markers (Fasn, D5d, D6d, Scd1, Lxrα). Metformin significantly attenuated diet-induced inflammation and 18:1n9 and 22:6n3 in fetal livers, as well as n3 fatty acids (p < 0.05). Prenatal obesogenic diet exposure significantly increased fetal liver IFNγ levels (p < 0.05), which was reversed by maternal metformin treatment (p < 0.05).ConclusionsConsumption of a high calorie diet significantly affected maternal and fetal fatty acid metabolism. It reduced anti-inflammatory polyunsaturated fatty acids in maternal and fetal livers, altered gene expression of fatty acid metabolism markers, and induced inflammation in the fetal livers. Prenatal metformin attenuated some diet-induced fatty acid changes and inflammation in the fetal livers without affecting maternal livers, suggesting that maternal metformin may impact fetal/neonatal fatty acid/lipid metabolism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0115-9) contains supplementary material, which is available to authorized users.

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Metformin versus insulin in gestational diabetes mellitus: a meta-analysis of randomized clinical trials

Abstract: Metformin may be beneficial in treating gestational diabetes. However, even more studies are needed to provide more evidence for the future use of metformin.

Cited by 26 publications

References 33 publications

The emerging role of metformin in gestational diabetes mellitus

The emerging role of metformin in gestational diabetes mellitus

Effectiveness of Metformin in the Prevention of Gestational Diabetes Mellitus in Obese Pregnant Women

The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism

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