Early Metformin Treatment for Gestational Diabetes

To the Editor A recent study concluded that early metformin treatment for gestational diabetes was not superior to placebo for the composite primary outcome. However, we have several concerns. First, the authors defined the primary outcome as a composite of insulin initiation before delivery or fasting blood glucose exceeding 5.1 mmol/L at week 32 or week 38 of gestation. Some studies have used different criteria, including new insulin initiation, increased use of glucose-lowering medications, or specific blood glucose measurements. We would like to know if there is an internationally recognized standard for these criteria, which could have been used to bolster result credibility. Second, this study lacked specific data about individuals in both groups who exceeded the 5.1-mmol/L blood glucose threshold at weeks 32 and 38. This omission could have affected the interpretation of the results. Third, the results suggested that metformin reduced insulin dosage, which may be an advantage over placebo. Should this reduction have been considered a primary outcome that deserved more emphasis? Fourth, it is unclear if insulin users were excluded from blood glucose measurements at weeks 32 and 38. Inclusion of these patients could have affected blood glucose control results and would no longer solely reflect the effect of metformin. Fifth, the study title suggested the primary focus should be evaluating outcomes for pregnant individuals and infants. In gestational diabetes, minor blood glucose differences after medication use may not be the primary concern. It is more important to assess metformin’s effect on outcomes of pregnant individuals and infants. The study conclusion, solely based on blood glucose not exceeding 5.1 mmol/L, might lead readers to believe that metformin had no effect compared with placebo. However, recent meta-analyses have indicated potential benefits of metformin for pregnant individuals and newborns. Therefore, clinicians should carefully consider the conclusions drawn from this study.