Short‐ and long‐term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta‐analysis

Abstract Aim To assess the short‐ and long‐term maternal and fetal impact of metformin in pregnancy compared with insulin. Methods We performed a comprehensive literature search of MEDLINE , EMBASE , BIOSIS , Cochrane Database of Systematic Reviews and ClinicalTrials.gov. Eligible studies were randomized control trials ( RCT s) or follow‐up of an RCT that: (1) compared metformin with insulin in pregnancy in women with gestational diabetes mellitus or Type 2 diabetes; and (2) reported maternal or fetal outcomes of interest. Two reviewers extracted the data, evaluated study quality and calculated pooled estimates. Results Sixteen studies ( n = 2165 in quantitative analysis) were included. Metformin lowered the risk of neonatal hypoglycaemia [risk ratio ( RR ) = 0.63; 95% confidence interval (95% CI ), 0.45 to 0.87], large for gestational age babies ( RR = 0.80; 95% CI , 0.64 to 0.99), pregnancy‐induced hypertension ( RR = 0.56; 95% CI , 0.37 to 0.85) and total maternal pregnancy weight gain [mean difference ( MD ) –2.07; 95% CI –2.88 to –1.27]. Metformin did not increase preterm delivery ( RR = 1.18; 95% CI 0.67 to 2.07), small for gestational age babies ( RR = 1.20; 95% CI , 0.67 to 2.14), perinatal mortality ( RR = 0.82; 95% CI , 0.17 to 3.92) or Caesarean section ( RR = 0.97; 95% CI , 0.80 to 1.19). Long‐term outcome information is limited. Conclusions Our review found that metformin had no short‐term adverse effects on pregnancy, potential benefits in the neonatal period, but limited long‐term follow‐up information. Prior to routine use, we recommend further follow‐up studies of offspring exposed to metformin in utero .