Metformin <i>versus</i> glyburide in treatment and control of gestational <i>diabetes mellitus</i>: a systematic review with meta-analysis

Oliveira, Marina Martins de; Andrade, Kayan Felipe de Oliveira; Lima, Giovanni Henrique Silva; Rocha, Thiago Casali

doi:10.31744/einstein_journal/2022RW6155

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REVIEW • Einstein (São Paulo) 20 • 2022 • https://doi.org/10.31744/einstein_journal/2022RW6155 copy

Metformin versus glyburide in treatment and control of gestational diabetes mellitus: a systematic review with meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective

To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus.

Methods

Studies published in English, in the last 10 years, in the databases MEDLINE^®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords “Gestational diabetes”, “Glyburide”, “Metformin” and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide.

Results

The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036).

Conclusion

The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.

Diabetes, gestational; Glyburide/therapeutic use; Metformin/therapeutic use

Inclusion criteria
Delimitation	Randomized controlled clinical trial
Patients	Women aged over 18 years with gestational age between 11-36 weeks diagnosed with GDM who have failed to control their blood glucose with lifestyle change measures
Intervention	Oral monotherapy: metformin
Control	Oral monotherapy: glyburide
Languages	In English only

Exclusion criteria

Delimitation	Unclear randomization process
Patients	Women with pre-DMG or first-trimester fasting glucose ≥105mg/dL, suspected intrauterine growth restriction before 24 weeks, and major fetal malformations
Intervention	Unclear or inappropriate interventions Need to combine other control intervention (adding another hypoglycemic agent and/or insulin)

Fundamental clinical outcomes

Maternal	Mode of delivery* Pregnancy weight gain* Fasting blood glucose* Postprandial blood glucose*
Neonatal	Birth weight* Macrosomia* Neonatal hypoglycemia^† Apgar score^† Intensive care^†

Study	Patients	Intervention and methods	Maternal and neonatal outcomes

			Birth weight	Neonatal hypoglycemia	Need for Caesarean section	Need for intensive care	Apgar score	Macrosomia	↓ Fasting blood glucose	↓ Post-prandial blood glucose	Weight gain in pregnancy
Nachum et al.⁽¹²⁾	104 women 53 GG 51 GM	GG: 2.5-20mg/day GM: 850-2,550mg/ day after meals	p=0.6 M=G*	p=0.09 M>G^†	p=0.7 M=G*		Apgar score>7 p=1 M=G*	>4,000g p=0.6 M=G*	p=0.2 M=G*	p=0.3 M=G*	p=0.8 M=G*
Silva et al.⁽¹³⁾	200 women 96 GG 104 GM	GG: 5-20mg/day GM: 1,000-2,500mg/day	p=0.01 M>G^†	p=0.81 M=G*	p=0.88 M=G*	p=0.94 M=G*	In 1’: p=0.56 Up to 5’: p=0.50 M=G*		p=0.18 M=G*	p=0.98 M=G*	p=0.04 M>G^†
Silva et al.⁽¹⁴⁾	72 women 40 GG 32 GM	GG: 5-20mg/day GM: 500-2,500mg/day	p=0.36 M=G*	p=0.89 M=G*	p=0.91 M=G*	p=0.23 M=G*	In 1’: p=0.57 In 5’: p=0.24 M=G*	>4kg p=0.24 M=G*	p=0.15 M=G*	p=0.10 M=G*	p=0.02 M>G^†
George et al.⁽¹⁵⁾	159 women 80 GG 79 GM	GG: 2.5-15mg/day GM: 500-2,500mg/day		p=0.001 M>G^†				>3.7kg p=0.73 M=G*	p=0.37 M=G*	p=0.28 M=G*
Moore et al.⁽¹⁶⁾	149 women 74 GG 75 GM	GG: 5-20mg/day GM: 500mg-2g/day	p=0.02 M>G^†	p=0.32 M=G*	p=0.02 G>M^‡	p=0.37 M=G*			p=0.23 M=G*	p=0.24 M=G*

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[1] Corresponding author: Marina Martins de Oliveira Alameda Salvaterra, 200 – Salvaterra Zip code: 36033-003 – Juiz de Fora, MG, Brazil Phone: (55 32) 2101-5000 E-mail: ninamaoli@hotmail.com