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Metformin for Medication-Associated Weight Gain in Youth with Autism Spectrum Disorder
Aggression, self-injurious behavior, and severe tantrums (referred to as “irritability”), are common targets of pharmacotherapy in youth with autism spectrum disorder (ASD). Placebo controlled trials have demonstrated the efficacy of risperidone and aripiprazole for treatment of ASD-associated irritability, resulting in FDA-approval of these medications. Unfortunately, antipsychotic treatment is associated with weight gain, changes in glucose and lipid metabolism, and poor cardiovascular outcomes, and youth with ASD may be at particular risk for these adverse effects. Emerging evidence suggests that metformin may have a role in treating medication-associated weight gain in youth with ASD.
Objectives:
In this study, we completed a retrospective chart review of youth with ASD treated with metformin targeting medication-associated weight gain with goal of deepening our understanding of the impact of this drug in our patient population.
Methods:
Via systematic review of electronic medical records, we identified 57 individuals with ASD age 2-20 years treated with metformin between July 2012 and February 2016. Demographic data, concomitant medications, metformin treatment duration, metformin dose, and BMI z-score at initiation and end of treatment were collected. Paired sample t-tests were used to evaluate change in BMI z-score with metformin treatment. A series of repeated ANOVA’s tested age, sex, duration of treatment, dose (initial and final) as possible moderators of BMI z-score change.
Results:
Participants were primarily male (81%), Caucasian (88%), and suffered from cognitive impairment (67%) and a disruptive behavior disorder (95%). Mean age was 13.6 (SD=2.7) years, mean duration of treatment with metformin was 1.96 (SD=1.7) years. Metformin doses ranged from 250 mg to 2000 mg, with mean starting dose of 772 mg (SD=361) and mean final dose 1173 mg (SD=536 mg). Ninety-one percent of participants received concomitant treatment with an antipsychotic throughout duration of metformin treatment, and nearly half received treatment with an antidepressant, alpha-2 agonist, or sleep aid. There was no change in frequency of concomitant medications by drug class over duration of study (all McNemar tests ps>0.15).
Mean baseline BMI z-score was 1.85 (SD=0.6), and mean final BMI z-score was 1.81 (SD=0.7). There was no significant change in BMI z-score between time points (t-value=0.58, p ns). Only metformin starting dose moderated change in BMI z-score from start to finish (F (1, 55)=4.25, p<0.05). Participants with metformin starting dose less than 1000 mg had no significant change (paired sample t-value=1.35, p>ns) in BMI z-score from start (M=1.63 (SD=0.7) to finish (M=1.72 (SD=0.7), whereas participants treated with starting dose 1000 mg or greater demonstrated significantly decreased BMI z-score (paired sample t-value=1.98, p>0.05) from start (M=2.06 (SD=0.5) to finish (M=1.85 (SD=0.6).
Conclusions:
In this naturalistic sample, metformin treatment appears to stabilize BMI z-score, but does not result in significant reduction of BMI z-score. Treatment dose appears to potentially moderate the effect of metformin, with higher starting doses resulting in greater reduction in BMI z-score over the course of treatment. Further work is indicated to determine the safety and efficacy of metformin as a treatment for medication-associated weight gain in youth with ASD.