Oral anti-diabetic pharmacological therapies for the treatment of women with gestational diabetes

Brown, Julie; Martis, Ruth; Hughes, Brenda; Rowan, Janet; Crowther, Caroline A

doi:10.1002/14651858.cd011967.pub2

Cited by 65 publications

(50 citation statements)

References 94 publications

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“…Preterm birth was increased in women who were treated with metformin. In contrast, a recent systematic review compared outcomes between women randomized to either glyburide or metformin from several additional studies and found no differences in maternal or neonatal outcomes 86. The authors noted that most of the studies comparing glyburide with metformin were of moderate to low quality, and they also stressed that the benefits and potential harms of one oral antidiabetic drug therapy compared with another are unclear.…”

Section: Glyburide Versus Metforminmentioning

confidence: 97%

Novel therapies for diabetes mellitus in pregnancy

Feghali

Scifres

2018

BMJ

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Diabetes is a common complication of pregnancy, and the prevalence of all types of the disease is increasing worldwide. Diabetes in pregnancy is associated with short term and long term adverse effects for mother and child. The goal of treatment of diabetes in pregnancy is to minimize maternal and fetal adverse events related to hyperglycemia. Treatment options vary by type of diabetes, from a focus on lifestyle modifications in gestational diabetes to continuous glucose monitoring and insulin pumps in pregestational diabetes. Nevertheless, given the commonality of hyperglycemia, considerable overlap exists in the treatment of different types of diabetes in pregnancy. Also, despite ongoing research on treatment of diabetes in pregnancy for decades, changes in the characteristics of the patient population have highlighted the limited effectiveness of different therapies. Specifically, despite the co-occurrence of obesity and diabetes, treatment recommendations including glycemic targets are not altered in such cases and a single optimal treatment strategy for each type of diabetes in pregnancy does not seem to exist. Rather, the approach to treating pregnant women with diabetes likely needs to be individualized to maximize the short term and long term health of mother and child. This article will review recent clinical studies to summarize established treatment strategies and introduce novel therapies for diabetes in pregnancy.

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Section: Glyburide Versus Metforminmentioning

confidence: 97%

Novel therapies for diabetes mellitus in pregnancy

Feghali

Scifres

2018

BMJ

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“…The evidence for the real‐world comparative effectiveness of metformin versus insulin, however, is limited and inconclusive. The most recent Cochrane review of oral antidiabetic agents for treating GDM could not recommend nor refute use of metformin for this purpose on the basis of available evidence …”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand

Landi

Radke

Boggess

et al. 2019

Pharmacoepidemiology and Drug

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Purpose To measure the comparative effectiveness of metformin versus insulin for initial pharmacological management of gestational diabetes mellitus (GDM). Methods We conducted a population‐based retrospective cohort study using administrative claims, maternity care, and laboratory result data from New Zealand. We followed pregnant women aged 15 to 45 from GDM diagnosis through delivery and assessed outcomes using maternity care and hospitalization data. We adjusted for covariates using inverse probability of treatment weights and multiple imputation for missing covariate information. We estimated unadjusted and adjusted risk ratios (RRs), risk differences (RDs) per 100, and 95% confidence intervals (CIs). Linear regression was used to estimate the association of treatment with birthweight. We stratified analyses by ethnicity and infant sex in prespecified sensitivity analyses. Results We compared 3818 metformin‐treated pregnancies with 3450 insulin‐treated pregnancies. We observed differences in treatment initiation by ethnicity, socioeconomic status, region, and calendar year. Treatment groups were similar in age, body mass index (BMI), and timing of diagnosis/treatment initiation. After adjustment, metformin was associated with reduced absolute risk of planned elective c‐section (RD = −2.3, 95% CI, −4.3 to −0.3), large for gestational age (RD = −3.7, 95% CI, −5.5 to −1.8), and neonatal hypoglycemia (RD = −5.0, 95% CI, −6.9 to −3.2) compared with insulin. There were no clinically meaningful differences in average birthweight between metformin‐ and insulin‐treated pregnancies. We observed variation in estimates by ethnicity and infant sex for some neonatal outcomes. Conclusion Metformin appears to be an effective treatment for women with GDM and may reduce risk of some adverse neonatal outcomes when compared with insulin.

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“…The current standard of care is to optimize maternal blood sugar levels before and during pregnancy [11]. While this has certainly decreased some perinatal morbidities, infants born to mothers with good glycemic control continue to have a higher risk of heart disease [12][13][14][15] and gestational diabetes can predispose infants to macrosomia and programmed cardiometabolic disease as adults, even if their mother was treated during pregnancy [16][17][18][19][20][21][22][23][24]. This suggests there are additional under-recognized, targetable risk factors including lipids.…”

Section: Introductionmentioning

confidence: 99%

Maternal High Fat Diet and Diabetes Disrupts Transcriptomic Pathways that Regulate Cardiac Metabolism and Cell Fate in Newborn Rat Hearts

Preston

Larsen

Eclov

et al. 2020

Preprint

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Background Children born to diabetic or obese mothers have a higher risk of heart disease at birth and later in life. Our previous work using chromatin immunoprecipitation sequencing revealed that late-gestation diabetes in combination with maternal high fat (HF) diet cause a distinct fuel-mediated epigenetic reprogramming of rat cardiac tissue during fetal cardiogenesis. The objective of the present study was to investigate the overall transcriptional signature of newborn offspring exposed to the combination of maternal diabetes and maternal HF diet. Methods Gene expression profiling from hearts of diabetes exposed, HF diet exposed, combination exposed and control newborn rats was compared for differential transcriptome expression. Functional annotation, pathway and network analysis was performed on statistically significant differentially expressed genes from the combination exposed group compared with controls. Downstream metabolic assessments included measurement of total and phosphorylated AKT2 and GSK3β assays, as well as quantification of glycolytic capacity by extracellular flux analysis and glycogen staining. Results Transcriptome analysis of newborn rat hearts showed significant changes in cardiac gene expression following exposure to maternal diabetes or HF diet individually, as well as the combination of diabetes + HF compared with controls. Reactome analyses identified expression changes in two key signaling cascades functionally prioritized in male control and combination exposed offspring hearts. These pathways included downregulation of the fibroblast growth factor (FGF) pathway and concomitant downstream PI3K/AKT activation canonically recognized as a regulator of cell metabolism, growth, and development. In contrast, the second pathway exhibited significant upregulation of mitoribosomal signaling that regulates mitochondrial biogenesis, mitophagy and cell fate. Focused bioinformatic analysis on mitochondrial genes enriched in the combination exposed dataset revealed genes associated with diverse aspects of mitochondrial structure, function, and dynamism. Functional biochemical, metabolic, and histochemical assays supported these transcriptome changes, confirming the essential role of mitochondrial energetics in facilitating diabetes- and diet-induced cardiac transcriptome remodeling and phenotype in offspring. Conclusions This study provides the first data accounting for the compounding effects of maternal hyperglycemia and hyperlipidemia on the developmental cardiac transcriptome, and elucidates nuanced and novel features of maternal diabetes and diet on intergenerational regulation of heart health.

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Oral anti-diabetic pharmacological therapies for the treatment of women with gestational diabetes

Cited by 65 publications

References 94 publications

Novel therapies for diabetes mellitus in pregnancy

Novel therapies for diabetes mellitus in pregnancy

Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand

Maternal High Fat Diet and Diabetes Disrupts Transcriptomic Pathways that Regulate Cardiac Metabolism and Cell Fate in Newborn Rat Hearts

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