The researchers identified 35 studies for inclusion in the meta-analysis, comparing metformin with insulin, glyburide and placebo for the following indications: gestational diabetes (27 studies; n=5,319); maternal obesity (4 studies, n=1,485); polycystic ovarian syndrome (PCOS; 3 studies, n=930); and pre-gestational insulin resistance (1 study, n=299).
Gestational weight gain
A similar and significant reduction in gestational weight gain was observed for all gestational diabetes groups: -1.57kg vs insulin (p=0.0004); -1.67kg vs glyburide (p=0.02) and -1.5kg vs placebo (p=0.001). Similarly, metformin use for maternal obesity or PCOS resulted in an average reduction in gestational weight gain of 0.89kg (p=0.04) and 2.4kg (p<0.0001), respectively, compared with placebo.
No significant difference in the risk of pre-eclampsia was observed for any single indication (gestational diabetes, PCOS or maternal obesity) irrespective of comparator agent (insulin, glyburide or placebo). However, when all indications were combined, there was a significant reduction in the likelihood of pre-eclampsia in women randomised to metformin (odds ratio [OR] 0.69; p=0.02 [based on 23 studies including 6,301 pregnancies]).
In addition, the researchers found that in women with obesity, randomisation to metformin was associated with a significant reduction in the likelihood of caesarean section.
The findings from the meta-analysis also show that the likelihood of gastrointestinal symptoms was significantly increased in women randomised to metformin versus other treatments (OR 2.43, p=0.0002).
Excessive gestational weight gain is associated with perinatal complications, including increased risk of fetal growth anomalies, risk of gestational diabetes, caesarean delivery and pre-eclampsia, as well as long-term health risks to the mother such as post-partum weight retention, obesity and increased risk of developing type 2 diabetes and cardiovascular disease.
The researchers state that as the average weight gain in pregnancies affected by gestational diabetes is 9kg, a reduction of 1.55kg (17%, as observed in their analysis) constitutes a potentially clinically significant reduction in total gestational weight gain.
They add that individual pregnant women may weigh the importance of limiting gestational weight gain or of avoiding gastrointestinal symptoms differently, and these findings may thus influence decision-making around metformin treatment in pregnancy.