Dr. Handen et al. Reply.

We thank Dr. Higdon et al. for their interest in our article on metformin and children with autism spectrum disorders (ASD) and for providing information about the MOBILITY study (a Patient-Centered Outcomes Research Institute (PCORI)-funded pragmatic clinical trial to examine the relative effectiveness of metformin plus healthy lifestyle instruction versus healthy lifestyle instruction alone).1 In our October 2017 article,2 we reported the results of a 16-week open-label extension study of a group of 61 children and adolescents with ASD prescribed second-generation antipsychotic medications (SGAs) who previously participated in a randomized controlled trial (RCT) of metformin for management of weight gain. Although Higdon et al. indicated that our study results were encouraging, they believed that the conclusion of the accompanying JAACAP editorial3 stating metformin be considered as an adjunct treatment for any child who is overweight and prescribed SGAs was premature. Instead, they recommended that the results of their current pragmatic trial for children with bipolar disorder (which includes some children with ASD and intellectual disability) would better provide information on relevant moderators and mediators of metformin's effects. Such information would be of use to clinicians in determining whether to prescribe metformin to their patients or to focus on lifestyle changes (or a combination of the 2).