A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol
Abstract Background Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperg...
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| Format: | Article |
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BMC
2022-09-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-022-06694-y |
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| author | F. Dunne C. Newman D. Devane A. Smyth A. Alvarez-Iglesias P. Gillespie M. Browne M. O’Donnell |
| author_facet | F. Dunne C. Newman D. Devane A. Smyth A. Alvarez-Iglesias P. Gillespie M. Browne M. O’Donnell |
| author_sort | F. Dunne |
| collection | DOAJ |
| description | Abstract Background Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM. Methods EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care. Women aged 18–50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (<10th centile), intolerance or contraindication to the use of metformin, shock or sepsis, current gestational hypertension or pre-eclampsia, significant gastrointestinal problems, congestive heart failure, severe mental illness or galactose intolerance are excluded. Intervention Immediate introduction of metformin or placebo in addition to MNT and usual care. Metformin is initiated at 500mg/day and titrated to a maximum dose of 2500mg over 10 days. Women are followed up at 4 and 12 weeks post-partum to assess maternal and neonatal outcomes. The composite primary outcome measure is initiation of insulin or fasting blood glucose ≥ 5.1 mmol/L at gestational weeks 32 or 38. The secondary outcomes are the time to insulin initiation and insulin dose required; maternal morbidity at delivery; mode and time of delivery; postpartum glucose status; insulin resistance; postpartum body mass index (BMI); gestational weight gain; infant birth weight; neonatal height and head circumference at delivery; neonatal morbidities (neonatal care unit admission, respiratory distress, jaundice, congenital anomalies, Apgar score); neonatal hypoglycaemia; cost-effectiveness; treatment acceptability and quality of life determined by the EQ5D-5L scale. Discussion The EMERGE trial will determine the effectiveness and safety of early and routine use of metformin in GDM. Trial registration EudraCT Number 2016-001644-19l; NCT NCT02980276 . Registered on 6 June 2017. |
| first_indexed | 2024-04-14T07:16:10Z |
| format | Article |
| id | doaj.art-97a2fddad0fa48dea1527adb70600310 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-14T07:16:10Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-97a2fddad0fa48dea1527adb706003102022-12-22T02:06:18ZengBMCTrials1745-62152022-09-0123111410.1186/s13063-022-06694-yA randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocolF. Dunne0C. Newman1D. Devane2A. Smyth3A. Alvarez-Iglesias4P. Gillespie5M. Browne6M. O’Donnell7Department of Medicine, HRB Clinical Research Facility, National University of Ireland GalwayDepartment of Medicine, HRB Clinical Research Facility, National University of Ireland GalwayHRB-Trials Methodology Research Network, National University of Ireland GalwayDepartment of Medicine, HRB Clinical Research Facility, National University of Ireland GalwayDepartment of Medicine, HRB Clinical Research Facility, National University of Ireland GalwayHealth Economics & Policy Analysis Centre (HEPAC), Institute for Lifecourse and Society (ILAS), National University of Ireland GalwayDepartment of Medicine, HRB Clinical Research Facility, National University of Ireland GalwayDepartment of Medicine, HRB Clinical Research Facility, National University of Ireland GalwayAbstract Background Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM. Methods EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care. Women aged 18–50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (<10th centile), intolerance or contraindication to the use of metformin, shock or sepsis, current gestational hypertension or pre-eclampsia, significant gastrointestinal problems, congestive heart failure, severe mental illness or galactose intolerance are excluded. Intervention Immediate introduction of metformin or placebo in addition to MNT and usual care. Metformin is initiated at 500mg/day and titrated to a maximum dose of 2500mg over 10 days. Women are followed up at 4 and 12 weeks post-partum to assess maternal and neonatal outcomes. The composite primary outcome measure is initiation of insulin or fasting blood glucose ≥ 5.1 mmol/L at gestational weeks 32 or 38. The secondary outcomes are the time to insulin initiation and insulin dose required; maternal morbidity at delivery; mode and time of delivery; postpartum glucose status; insulin resistance; postpartum body mass index (BMI); gestational weight gain; infant birth weight; neonatal height and head circumference at delivery; neonatal morbidities (neonatal care unit admission, respiratory distress, jaundice, congenital anomalies, Apgar score); neonatal hypoglycaemia; cost-effectiveness; treatment acceptability and quality of life determined by the EQ5D-5L scale. Discussion The EMERGE trial will determine the effectiveness and safety of early and routine use of metformin in GDM. Trial registration EudraCT Number 2016-001644-19l; NCT NCT02980276 . Registered on 6 June 2017.https://doi.org/10.1186/s13063-022-06694-yMetforminGestational diabetes mellitusPregnancyRandomised controlled trial |
| spellingShingle | F. Dunne C. Newman D. Devane A. Smyth A. Alvarez-Iglesias P. Gillespie M. Browne M. O’Donnell A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol Trials Metformin Gestational diabetes mellitus Pregnancy Randomised controlled trial |
| title | A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol |
| title_full | A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol |
| title_fullStr | A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol |
| title_full_unstemmed | A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol |
| title_short | A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol |
| title_sort | randomised placebo controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects emerge study protocol |
| topic | Metformin Gestational diabetes mellitus Pregnancy Randomised controlled trial |
| url | https://doi.org/10.1186/s13063-022-06694-y |
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