The Effectiveness of Metformin in Managing Second Generation Antipsychotic-Induced Weight Gain in Children and Adolescents.

Objective: This study aimed to assess the effectiveness of metformin for antipsychotic-induced weight gain (AIWG) and determine whether the timing of metformin initiation and premorbid obesity moderated metformin effectiveness in children and adolescents on treatment with second-generation antipsychotics (SGAs).

Methods: A cohort of individuals 6 to 17 years of age, from 2016 to 2021, initiating a new SGA treatment and receiving a subsequent metformin prescription during SGA treatment were identified from the IQVIA Ambulatory EMR-US database. The changes in body mass index (BMI) z score before and after metformin initiation were assessed using the piecewise linear mixed-effects regression model.

Results: The results showed that the initiation of metformin was associated with a flattening out of the prior-metformin BMI z score trend. Relative to those who did not use metformin, metformin users had an additional monthly decrease in BMI z score of -0.053 (P = .0008) during the 6-month period after metformin initiation. Specifically, users who were non-obese before the intervention experienced a greater reduction in the BMI z score slope compared to those who were mildly-to-moderately obese and severely obese (non-obese - mildly-to-moderately obese: -0.07631, P = .0001; non-obese - severely obese: -0.09613, P < .0001). A different effect was not observed between patients who initiated metformin within versus beyond 90 days of SGA initiation. Extending the observation period to 12 months yielded comparable findings.

Conclusions: Adjuvant metformin helps manage AIWG in children and adolescents by flattening the upward AIWG trend rather than reversing it. The effect was more prominent before the development of obesity, suggesting that the early introduction of metformin for AIWG management may be warranted.