Metformin versus insulin for gestational diabetes: a systematic review and meta-analysis

Abstract

Background

Metformin is increasingly used in clinical practice for the treatment of gestational diabetes mellitus. However, its safety and long-term effects on fetuses exposed to metformin in uterus remain controversial.

Methods

We systematically searched PubMed, Embase, and the Cochrane database (last search was updated on 1 May 2019) for randomized controlled trials comparing metformin with insulin. Two reviewers extracted the data and calculated pooled estimates by use of a random-effects model.

Results

Twenty-four studies were included. Among these, seventeen RCTs (N = 2828 participants) were included for quantitative analyses and seven studies were included only for qualitative synthesis. Metformin lowered the risk of pregnancy-induced hypertension (p = .03; risk ratio (RR) = 0.64; confidence interval (95%CI) [0.44, 0.95]), large for gestational age babies (p = .04; RR = 0.82; 95% CI [0.68, 0.99]), macrosomia (p = .01; RR = 0.63; 95%CI [0.45, 0.90]), neonatal hypoglycemia (p = .001; RR = 0.72; 95%CI [0.59, 0.88]), and neonatal intensive care unit admission (p = .01; RR = 0.74; 95%CI [0.58, 0.94]). Metformin did not increase premature delivery (p = .11; RR = 1.28; 95%CI [0.95, 1.73]), preeclampsia (p = .45; RR = 0.89; 95%CI [0.65, 1.21]), caesarean delivery (p = .20; RR = 0.94; 95%CI [0.85, 1.04]), small for gestational age babies (p = .95; RR = 0.99; 95%CI [0.69, 1.42]). The long-term results seemed to have no adverse effect, but the information was still limited.

Conclusions

According to our review, metformin may have potential benefits for pregnant women and newborns with no obvious adverse effects. However, even more studies are needed to provide evidence for the future use of metformin.

Keywords:

• Gestational diabetes mellitus
• insulin
• meta-analysis
• metformin
• randomized control trials

Author contributions

Le-xin Bao had the idea for the study. Le-xin Bao and Wan-ting Shi selected studies for inclusion and abstracted data. Wan-ting Shi did the statistical analyses. Le-xin Bao and Yu-xin Han interpreted the data. Le-xin Bao and Wan-ting Shi wrote the first draft.

Statement of ethics

All analyses were based on the previous published studies, thus no ethical approval and patient consent are required.

Disclosure statement

No potential conflict of interest was reported by the authors.