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Metformin associated with decreasing weight gain in kids with autism

August 24, 2016

The diabetes medication metformin hydrochloride was associated with decreased weight gain in a small clinical trial of children and adolescents with autism spectrum disorder who were taking atypical antipsychotics to treat symptoms of irritability and agitation, according to an article published online by JAMA Psychiatry.

The atypical (newer) antipsychotic medications risperidone and aripiprazole are the only treatments the U. S. Food and Drug Administration has approved for use in autism spectrum disorder (ASD). While the medications can improve symptoms of irritability and agitation in children, the medicines also cause weight gain. Over time, that can increase the risk of diabetes. In adults, metformin has been associated with stopping or reversing the weight gain associated with atypical antipsychotics.

Evdokia Anagnostou, M.D., of the Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada, and coauthors conducted a 16-week clinical trial to test the efficacy of metformin for weight gain associated with atypical antipsychotics in children and adolescents with ASD.

The clinical trial assigned 61 participants (average age almost 13) to receive either metformin or placebo twice daily. Of the 61 participants, 60 initiated treatment. The study's main outcome measure was change in body mass index (BMI) z score over 16 weeks of treatment as a reflection of weight gain. They also looked at other body composition and metabolic variables, as well as safety and tolerability.

The authors report metformin was better than placebo in reducing weight gain associated with atypical antipsychotics, as assessed by change from baseline to week-16 BMI z scores (metformin vs placebo difference of ?0.010).

Of the 28 participants in the metformin group who initiated treatment, three participants (11 percent) saw declines of 8 percent to 9 percent in BMI. No other participants experienced declines of more than 5 percent in BMI during the 16-week treatment, according to the results. No significant differences were noted in metabolic variables.

The authors report that, overall, metformin was well tolerated, although participants experienced gastrointestinal adverse events during a higher percentage of treatment days.

Study limitations include a small group of participants and a too short period of time to evaluate whether the initial improvement can be maintained.

"These findings have important implications for children in whom the benefits of atypical antipsychotics for treating irritability and agitation symptoms are difficult to balance with the substantial weight gain that often accompanies their use," the study concludes.

(JAMA Psychiatry. Published online August 24, 2016. doi:10.1001/jamapsychiatry.2016.1232. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: The article contains conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Atypical Antipsychotic-Induced Weight Gain in Children, Adolescents

"Clearly, Anagnostou et al understand the dilemma our field faces in balancing the risk-benefit ratio of treating youths with ASD with atypical antipsychotics. They have identified a potential medication cotreatment to help mitigate the weight gain associated with atypical antipsychotic use in children with ASD. They also realize the limitations of their study. ... Larger and longer-term studies of metformin administration in youths with ASD treated with an atypical antipsychotic will be important to address these concerns and remaining questions," writes Christopher J. McDougle, M.D., of Massachusetts General Hospital and Harvard Medical School, Lexington, Mass., in a related editorial.

(JAMA Psychiatry. Published online August 24, 2016. doi:10.1001/jamapsychiatry.2016.1213. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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The JAMA Network Journals

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