Metformin efficacy and safety as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled trial

Background: Antidiabetic medications have shown efficacy in alleviating autism symptoms. However, there is a lack of clinical research on the impact of metformin on irritability associated with autism. This study aimed to assess the efficacy and safety of metformin as an adjuvant therapy with risperidone for managing irritability in children diagnosed with Autism Spectrum Disorder (ASD).Methods: This is a randomized, 10-week, double-blind, placebo-controlled trial conducted at the children's autism clinic of Roozbeh Hospital (Tehran, Iran) from March 2024 to May 2024. Participants were divided into two groups of risperidone plus metformin (500 mg per day) and risperidone plus placebo and were assessed at baseline, weeks 5 and 10 with the aberrant behavior checklist-community scale (ABC-C).Results: A total of 55 patients were included in the final analysis. Irritability (primary outcome measure) sharply decreased in the metformin compared to the placebo group (p = 0.008). Among the other four subscales of ABC-C, the hyperactivity/noncompliance score showed a significant drop during the baseline-to-week-5 period (p = 0.021). In addition, inappropriate speech subscales decreased significantly from baseline-to-week 5 in the metformin compared to the placebo group (p = 0.045). No other significant finding was observed among ABC-C scores for lethargy/social withdrawal or stereotypic behavior subscales.Conclusion: Metformin demonstrated promising results in reducing irritability in ASD patients, which is in concordance with previous studies. However, further studies are required before any broad clinical recommendation.