A meta-analysis of 17 studies (both RCT and non-RCT) with 2,899 participants demonstrated reduced incidence of early miscarriage, preterm delivery, preeclampsia, GD, the need for insulin treatment and maternal weight gain.58 Another meta-analysis of 11 RCTs found that metformin does not lower the risk of GD in high-risk individuals with obesity, PCOS or pre-existing insulin resistance.59 Another meta-analysis of six RCTs involving 1,229 participants showed benefit only in the risk of preterm delivery but did not affect the incidence of GD, miscarriage, preeclampsia and birthweight.60 This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.