Metformin in the management of diabetes during pregnancy and lactation

Abstract

This review explores the current place of metformin in the management of gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation. The rationale and basic pharmacology of metformin usage in pregnancy is discussed along with the evidence from observational and randomized controlled trials in women with GDM or overt diabetes. There seems to be adequate evidence of efficacy and short-term safety of metformin in relation to maternal and neonatal outcomes in GDM, with possible benefits related to lower maternal weight gain and lower risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the advantages of oral administration, convenience, less cost and greater acceptability. Metformin may, therefore, be considered in milder forms of GDM where glycemic goals are not attained by lifestyle modification. However, failure rate is likely to be higher in those with an earlier diagnosis of GDM, higher blood glucose, higher body mass index (BMI) or previous history of GDM, and insulin remains the cornerstone of pharmacological treatment in such cases. The use of metformin in type 2 diabetes has been assessed in observational and small randomized trials. Metformin monotherapy in women with overt diabetes is highly unlikely to achieve glycemic targets. Hence, the use should be restricted as adjunct to insulin and may be considered in women with high insulin dose requirements or rapid weight gain. There is clearly a need for more clinical trials to assess the effect of combined insulin plus metformin therapy in pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long-term effects in offspring exposed to metformin in utero. It is imperative to further explore its impact on offspring as metformin has significant transplacental transfer and has the potential to impact the programming of the epigenome. Therefore, caution must be exercised when prescribing metformin in pregnant women. More research is clearly needed before metformin can be considered as standard of care in the management of diabetes during pregnancy.

Metformin Decreases Hyaluronan Synthesis by Vascular Smooth Muscle Cells

“…Also effects on DNA methylation by metformin have been reported 58. Currently, the long-term effects of gestational metformin treatment are unknown 59. In our study, gestational metformin treatment caused structural changes in offspring mice aorta wall structure by decreasing the amount of HA.…”

Maternal and neonatal outcomes following a diabetic pregnancy within the context ofHIV

“…Neither OHA negatively influenced PNM when compared to insulin. This contributes to the evidence that these agents may be a safe alternative to insulin in our setting …”

“…This contributes to the evidence that these agents may be a safe alternative to insulin in our setting. 13,40 Limitations of our study are related to the retrospective study design, resulting in missing data due to under-reporting in files, including BMI, HIV status and treatment details, possible rates of pre-eclampsia/ eclampsia, and some neonatal outcomes (hypoglycemia, jaundice, and respiratory distress syndrome). Moreover, we did not have data on prepregnancy BMI and the use of BMI at initial presentation unadjusted for gestational age could have resulted in an overestimation of rates of obesity and overweight.…”

Auditoria De Um Serviço De Atendimento De Gestantes Portadoras De Diabetes Mellitus Gestacional

“…Neste estudo, 34,3% das gestantes diabéticas efetuaram controle glicêmico apenas com dietoterapia, enquanto na população de Neta et al 24 , uma porcentagem bastante superior de gestantes (78,0%) obteve sucesso apenas com tratamento não medicamentoso. Se após duas semanas de dieta os níveis glicêmicos permanecerem elevados, devese iniciar tratamento farmacológico 6 , o qual é necessário para 20% a 60% das pacientes com DMG 25 . Porém, encontrou-se que 65,7% das gestantes necessitaram de terapia com metformina, insulina ou da associação de ambas.…”

“…A taxa de sucesso na terapêutica com a metformina nas gestantes portadoras de DMG em ensaios clínicos randomizados varia entre 53 e 75% 27 . Outro estudo 25 apontou que 46,3% dos pacientes tratados com metformina necessitaram de insulina suplementar. Na população analisada, a monoterapia com metformina foi o tratamento mais prevalente, eficaz em 41,0% das gestantes, o que diminuiu a necessidade da associação de insulina à terapêutica, que foi necessária para 12,2% das pacientes que faziam uso de metformina.…”