Dataset Information

Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis.

ABSTRACT:

Objective

To summarize short term outcomes in randomized controlled trials comparing glibenclamide or metformin versus insulin or versus each other in women with gestational diabetes requiring drug treatment.

Design

Systematic review and meta-analysis.

Eligibility criteria for selecting studies

Randomized controlled trials that fulfilled all the following: (1) published as full text; (2) addressed women with gestational diabetes requiring drug treatment; (3) compared glibenclamide v insulin, metformin v insulin, or metformin v glibenclamide; and (4) provided information on maternal or fetal outcomes.

Data sources

Medline, CENTRAL, and Embase were searched up to 20 May 2014.

Outcomes measures

We considered 14 primary outcomes (6 maternal, 8 fetal) and 16 secondary (5 maternal, 11 fetal) outcomes.

Results

We analyzed 15 articles, including 2509 subjects. Significant differences for primary outcomes in glibenclamide v insulin were obtained in birth weight (mean difference 109 g (95% confidence interval 35.9 to 181)), macrosomia (risk ratio 2.62 (1.35 to 5.08)), and neonatal hypoglycaemia (risk ratio 2.04 (1.30 to 3.20)). In metformin v insulin, significance was reached for maternal weight gain (mean difference -1.14 kg (-2.22 to -0.06)), gestational age at delivery (mean difference -0.16 weeks (-0.30 to -0.02)), and preterm birth (risk ratio 1.50 (1.04 to 2.16)), with a trend for neonatal hypoglycaemia (risk ratio 0.78 (0.60 to 1.01)). In metformin v glibenclamide, significance was reached for maternal weight gain (mean difference -2.06 kg (-3.98 to -0.14)), birth weight (mean difference -209 g (-314 to -104)), macrosomia (risk ratio 0.33 (0.13 to 0.81)), and large for gestational age newborn (risk ratio 0.44 (0.21 to 0.92)). Four secondary outcomes were better for metformin in metformin v insulin, and one was worse for metformin in metformin v glibenclamide. Treatment failure was higher with metformin than with glibenclamide.

Conclusions

At short term, in women with gestational diabetes requiring drug treatment, glibenclamide is clearly inferior to both insulin and metformin, while metformin (plus insulin when required) performs slightly better than insulin. According to these results, glibenclamide should not be used for the treatment of women with gestational diabetes if insulin or metformin is available.Systematic review registration NCT01998113.

SUBMITTER: Balsells M

PROVIDER: S-EPMC4301599 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown. METHODS AND FINDINGS:PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and the Cochrane database were systematically searched (from database inception to 26 February 2019). Outcomes of GDM-affected pregnancies randomised to treatment with metformin versus insulin were included (randomised controlled trials and prospective randomised controlled studies) from cohorts including European, American, Asian, Australian, and African women. Studies including pregnant women with pre-existing diabetes or non-diabetic women were excluded, as were trials comparing metformin treatment with oral glucose-lowering agents other than insulin. Two reviewers independently assessed articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Outcome measures were parameters of fetal, infant, and childhood growth, including weight, height, BMI, and body composition. In total, 28 studies (n = 3,976 participants) met eligibility criteria and were included in the meta-analysis. No studies reported fetal growth parameters; 19 studies (n = 3,723 neonates) reported measures of neonatal growth. Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7, I2 = 83%, p = 0.005) and lower ponderal indices (mean difference -0.13 kg/m3, 95% CI -0.26 to 0.00, I2 = 0%, p = 0.04) than neonates of insulin-treated mothers. The odds of macrosomia (odds ratio [OR] 0.59, 95% CI 0.46 to 0.77, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99, p = 0.04) were lower following maternal treatment with metformin compared to insulin. There was no difference in neonatal height or incidence of small for gestational age between groups. Two studies (n = 411 infants) reported measures of infant growth (18-24 months of age). In contrast to the neonatal phase, metformin-exposed infants were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830, I2 = 4%, p = 0.03). Three studies (n = 520 children) reported mid-childhood growth parameters (5-9 years). In mid-childhood, BMI was significantly higher (mean difference 0.78 kg/m2, 95% CI 0.23 to 1.33, I2 = 7%, p = 0.005) following metformin exposure than following insulin exposure, although the difference in absolute weights between the groups was not significantly different (p = 0.09). Limited evidence (1 study with data treated as 2 cohorts) suggested that adiposity indices (abdominal [p = 0.02] and visceral [p = 0.03] fat volumes) may be higher in children born to metformin-treated compared to insulin-treated mothers. Study limitations include heterogeneity in metformin dosing, heterogeneity in diagnostic criteria for GDM, and the scarcity of reporting of childhood outcomes. CONCLUSIONS:Following intrauterine exposure to metformin for treatment of maternal GDM, neonates are significantly smaller than neonates whose mothers were treated with insulin during pregnancy. Despite lower average birth weight, metformin-exposed children appear to experience accelerated postnatal growth, resulting in heavier infants and higher BMI by mid-childhood compared to children whose mothers were treated with insulin. Such patterns of low birth weight and postnatal catch-up growth have been reported to be associated with adverse long-term cardio-metabolic outcomes. This suggests a need for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure. This review protocol was registered with PROSPERO under registration number CRD42018117503.

Project description:ObjectiveTo investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors.DesignSystematic review and meta-analysis.Data sourcesWeb of Science, PubMed, Medline, and Cochrane Database of Systematic Reviews, from 1 January 1990 to 1 November 2021.Review methodsCohort studies and control arms of trials reporting complications of pregnancy in women with gestational diabetes mellitus were eligible for inclusion. Based on the use of insulin, studies were divided into three subgroups: no insulin use (patients never used insulin during the course of the disease), insulin use (different proportions of patients were treated with insulin), and insulin use not reported. Subgroup analyses were performed based on the status of the country (developed or developing), quality of the study, diagnostic criteria, and screening method. Meta-regression models were applied based on the proportion of patients who had received insulin.Results156 studies with 7 506 061 pregnancies were included, and 50 (32.1%) showed a low or medium risk of bias. In studies with no insulin use, when adjusted for confounders, women with gestational diabetes mellitus had increased odds of caesarean section (odds ratio 1.16, 95% confidence interval 1.03 to 1.32), preterm delivery (1.51, 1.26 to 1.80), low one minute Apgar score (1.43, 1.01 to 2.03), macrosomia (1.70, 1.23 to 2.36), and infant born large for gestational age (1.57, 1.25 to 1.97). In studies with insulin use, when adjusted for confounders, the odds of having an infant large for gestational age (odds ratio 1.61, 1.09 to 2.37), or with respiratory distress syndrome (1.57, 1.19 to 2.08) or neonatal jaundice (1.28, 1.02 to 1.62), or requiring admission to the neonatal intensive care unit (2.29, 1.59 to 3.31), were higher in women with gestational diabetes mellitus than in those without diabetes. No clear evidence was found for differences in the odds of instrumental delivery, shoulder dystocia, postpartum haemorrhage, stillbirth, neonatal death, low five minute Apgar score, low birth weight, and small for gestational age between women with and without gestational diabetes mellitus after adjusting for confounders. Country status, adjustment for body mass index, and screening methods significantly contributed to heterogeneity between studies for several adverse outcomes of pregnancy.ConclusionsWhen adjusted for confounders, gestational diabetes mellitus was significantly associated with pregnancy complications. The findings contribute to a more comprehensive understanding of the adverse outcomes of pregnancy related to gestational diabetes mellitus. Future primary studies should routinely consider adjusting for a more complete set of prognostic factors.Review registrationPROSPERO CRD42021265837.