Effects of Metformin on children with Fragile X Syndrome: a randomized, double-blind, placebo-controlled trial.

The study was underpowered for the primary outcome; the sample size calculation anticipated a larger effect, and the null primary result means secondary findings should be interpreted with caution. The cohort consisted entirely of males, so results may not generalize to females with Fragile X Syndrome. The Griffiths Development Scale (GDS-C) was only applicable to children under 8 years, leading to missing data for older participants in the developmental analysis. Many outcomes relied on caregiver reports, which can introduce bias, especially in an unblinded real-world context, though the trial itself was double-blind. The six-month duration is too short to assess long-term safety or sustained efficacy.

The study was funded by Fudan Children's Hospital, the Anhui Provincial Natural Science Foundation, and the China Medical Board. The authors declared no conflicts of interest.

Do not conclude that metformin is an effective treatment for Fragile X Syndrome based on the positive hyperactivity and sleep results. The primary outcome was null, meaning the overall behavioral benefit was not statistically significant. These secondary findings may be chance occurrences or specific to this small, male-only cohort, and require confirmation in larger trials before changing clinical practice.