The use of oral hypoglycaemic agents in pregnancy

Holt, Richard; Lambert, Kimberley

doi:10.1111/dme.12376

Cited by 41 publications

(30 citation statements)

References 68 publications

(99 reference statements)

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“…Furthermore, potential advantages are associated with the use of metformin compared with insulin to treat hyperglycaemia, including, consistently less gestational weight gain (pooled mean difference −1.14 kg; 95% CI −2.22 to −0.006), increased levels of self-reported maternal satisfaction (evaluated using questionnaires) and a reduced incidence of neonatal hypoglycaemia (pooled risk ratio 0.78 (95% CI 0.60-1.01)) in pregnant women 75,76 . PCOS is characterized by hyperandrogenism, hyperinsulinaemia and polycystic ovaries 77 .…”

Section: Pharmacological Preventionmentioning

confidence: 99%

Gestational diabetes mellitus: does an effective prevention strategy exist?

et al. 2016

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The overall incidence of gestational diabetes mellitus (GDM) is increasing worldwide. Preventing pathological hyperglycaemia during pregnancy could have several benefits: a reduction in the immediate adverse outcomes during pregnancy, a reduced risk of long-term sequelae and a decrease in the economic burden to healthcare systems. In this Review we examine the evidence supporting lifestyle modification strategies in women with and without risk factors for GDM, and the efficacy of dietary supplementation and pharmacological approaches to prevent this disease. A high degree of heterogeneity exists between trials so a generalised recommendation is problematic. In population studies of dietary or combined lifestyle measures, risk of developing GDM is not improved and those involving a physical activity intervention have yielded conflicting results. In pregnant women with obesity, dietary modification might reduce fetal macrosomia but in these patients, low compliance and no significant reduction in the incidence of GDM has been observed in trials investigating physical activity. Supplementation with probiotics or myoinositol have reduced the incidence of GDM but confirmatory studies are still needed. In randomized controlled trials, metformin does not prevent GDM in certain at-risk groups. Given the considerable potential for reducing disease burden, further research is needed to identify strategies that can be easily and effectively implemented on a population level.

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Section: Pharmacological Preventionmentioning

confidence: 99%

Gestational diabetes mellitus: does an effective prevention strategy exist?

et al. 2016

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“…The prevalence of pregnancy complicated by diabetes and/or gestational diabetes mellitus has been increasing [1]. Hyperglycaemia during pregnancy substantially increases the risk, for both mother and fetus, of developing various complications [2], which can be prevented by vigorous glycaemic control with insulin and/or metformin [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Successful pregnancy outcomes in a patient with type A insulin resistance syndrome

Enkhtuvshin¹,

Nagashima²,

Saito³

et al. 2015

Diabet. Med.

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BackgroundThe management of severe insulin resistance during pregnancy is challenging because of the increased risk of perinatal complications for both mother and fetus. We describe two consecutive pregnancies in a patient with severe insulin resistance caused by a mutation in the β subunit of the insulin receptor.Case reportA non‐obese Japanese woman was diagnosed as having diabetes mellitus during her first pregnancy at age 31 years. She presented at 6 weeks' gestation with a fasting plasma glucose concentration of 15.1 mmol/l and an HbA1c level of 95 mmol/mol (10.8%). Fasting insulin concentration was high at 68.8 μU/ml, suggesting severe insulin resistance. Anti‐insulin and insulin‐receptor antibodies were both negative. Genetic analysis revealed an in‐frame heterozygous deletion mutation (∆Leu999) in the insulin receptor gene. Despite large daily doses (up to 480 units per day) of insulin aspart and isophane, the patient's postprandial plasma glucose level exceeded 11.1 mmol/l. In the patient's second pregnancy, the addition of metformin at a dose of 2250 mg per day achieved tighter glycaemic control, with lower doses of insulin lispro and isophane (up to 174 units/day). Both newborns, who were found to carry the same mutation, were small for gestational age and developed transient hypoglycaemia after birth.ConclusionAdding metformin to the conventional insulin regimen effectively achieved tight glycaemic control with a lower dose of insulin. The mutation of the insulin receptor gene might underlie the intrauterine growth retardation of the newborns. To our knowledge, this is the first report of successful management of diabetes mellitus in a pregnant woman with type A insulin resistance syndrome.

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“…However, there have been reports of growth retardation, delayed ossification and miscarriage in pregnant rats and rabbits treated with DPP-4 inhibitors. 9 Studies in rats treated with SGLT-2 inhibitors have shown toxicity in developing kidneys, with an increased incidence and/or severity of renal pelvic and tubular dilatations in the time-period corresponding to the second and third trimesters of human pregnancy. 9 In addition, as mentioned in the labels for DPP-4 inhibitors and SGLT2-inhibitors, these agents have been shown to cross the placenta and to be excreted into breast milk in animal studies.…”

Section: Introductionmentioning

confidence: 99%

“…9 Studies in rats treated with SGLT-2 inhibitors have shown toxicity in developing kidneys, with an increased incidence and/or severity of renal pelvic and tubular dilatations in the time-period corresponding to the second and third trimesters of human pregnancy. 9 In addition, as mentioned in the labels for DPP-4 inhibitors and SGLT2-inhibitors, these agents have been shown to cross the placenta and to be excreted into breast milk in animal studies. However, reports on safety and outcomes in pregnant women who were exposed to these newer glucose-lowering agents are very scarce or non-existing.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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The need for appropriate registration of pregnancy outcomes under newer oral glucose‐lowering therapies

Benhalima

Mathiesen

Paldánius

et al. 2018

Diabetes Obesity Metabolism

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Funding information K. B. is the recipient of a Clinical DoctoralScholarship of the academic fund of UZ Leuven.Because of the increase in type 2 diabetes (T2DM) in young adults, women of childbearing age are frequently treated with newer glucose-lowering therapies, and an increase in unintentional exposure to therapies unapproved for use during pregnancy is expected. The clinician is left with the dilemma of deciding between discontinuation of a novel agent that is providing excellent glycaemic control, while switching to other agents may cause deterioration of glycaemia, and continued use of novel agents that may have uncertain effects on the unborn child. For T2DM, pregnancy data are collected only via spontaneous reporting systems. Therefore, we evaluated the available data on pregnancy outcomes under newer glucose-lowering agents in pharmaceutical safety databases. We found that data on pregnancy outcomes with new glucose-lowering agents in T2DM are scarce, with a high risk of bias towards negative outcomes, limiting their usefulness in robustly assessing safety. Because of the lack of information at present, these agents are not recommended for use during pregnancy or when planning pregnancy. To better guide clinical practice, structured systems of assessing pregnancy outcomes in women receiving these novel agents are urgently needed.antidiabetic drugs, database research, outcomes, pregnancy, safety, type 2 diabetes 1 | INTRODUCTION As type 2 diabetes (T2DM) becomes more prevalent and affects a younger population, the number of women of childbearing age with T2DM will increase. In many countries, the proportion of pregnant women with T2DM has risen to nearly half of all pregnant women with diabetes, with T2DM pregnancies outnumbering type 1 diabetes (T1DM) pregnancies in some metropolitan areas. 1 Women with T2DM are at equally high risk as those with T1DM of adverse pregnancy outcomes such as congenital anomalies and stillbirths. 1 Preconception care, with the aim of optimizing glycaemic control, can reduce adverse pregnancy outcomes. 1 While preconception care for women with T1DM is facilitated through follow-up at diabetes services, women with T2DM often fail to take advantage of this available care.In addition, many pregnancies in women with T2DM are unplanned. 2,3 Because of the potential implications of transplacental passage of oral glucose-lowering agents for the developing fetus, and because of the long-standing experience and efficacy of insulin during pregnancy, insulin is generally recommended as the first-choice treatment during pregnancy to achieve good glycaemic control. 4 Experience with oral hypoglycaemic agents, such as metformin and glibenclamide, during pregnancy mostly concerns women with gestational diabetes. 5,6 In addition, there is a paucity of long-term follow-up data on children exposed to these agents in utero. 7 Recent data suggest significantly increased rates of overweight and obesity in a cohort of 4-year-old children of mothers with polycystic ovarian syndrome who were expose...

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The use of oral hypoglycaemic agents in pregnancy

Cited by 41 publications

References 68 publications

Gestational diabetes mellitus: does an effective prevention strategy exist?

Gestational diabetes mellitus: does an effective prevention strategy exist?

Successful pregnancy outcomes in a patient with type A insulin resistance syndrome

The need for appropriate registration of pregnancy outcomes under newer oral glucose‐lowering therapies

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