Metformin effect on obese children differs by pubertal stage
By Marilynn Larkin
NEW YORK (Reuters Health) - Metformin may decrease body mass index (BMI) and cardiovascular-related obesity risks in prepubertal but not pubertal children, researchers in Spain suggest.
Metformin has demonstrated effectiveness in treating obesity in adults, but little research has been done in children.
To investigate, Dr. Concepcion Aguilera of the University of Granada, Spain and colleagues recruited 80 prepubertal and 80 pubertal obese, nondiabetic children ages seven to 14 with BMIs above the 95th percentile.
Participants received metformin or placebo for six months. They were instructed to gradually increase their dosage by taking 50 mg twice daily for 10 days, followed by 500 mg twice daily until the end of the study. They had a baseline physical and two additional assessments at two-month intervals.
As reported online June 12 in Pediatrics, 67 prepubertal and 73 pubertal children (72 boys) completed the study.
Metformin decreased the BMI z score (measure of relative weight adjusted for child age and sex) versus placebo in the prepubertal group (−0.8 and −0.6, respectively; P=0.04).
Prepubertal children in the metformin group also experienced significant increases in the quantitative insulin sensitivity check index (0.010 and −0.007; P=0.01) and the adiponectin-leptin ratio (0.96 and 0.15; P=0.01).
Inflammatory markers also declined in the metformin group, including interferon-gamma (−5.6 and 0; P=0.02) and total plasminogen activator inhibitor-1 (−1.7 and 2.4; P=0.04).
By contrast, there were no changes in the pubertal metformin group compared to the placebo group.
No serious adverse effects were reported.
Editorialist Dr. Paul Kaplowitz of Children’s National Health System in Washington, DC, told Reuters Health the study “is one of many which has shown very modest effects of metformin on weight loss in obese children.”
“Although the authors found a statistically significant effect of metformin in reducing BMI only in prepubertal patients, other studies have found it works in some pubertal patients as well,” he said by email. “The difference may be the relatively low dose of metformin used in this study, which was the same for prepubertal and pubertal children.”
“While this study did not examine the effect of metformin on food intake, other studies suggest metformin does have a dose-dependent effect on food intake and satiety,” he continued. “That may be the key to why some patients are able to lose weight on this drug.”
“Unfortunately, most of the metformin studies which have reported a decrease in BMI, including this one, have only lasted six months, and there is no evidence that longer term treatment provides any additional benefit,” Dr. Kaplowitz observed.
“Therefore, metformin should not be considered a primary weight loss treatment,” he said. However, because evidence in obese adults suggests that metformin curbs progression from prediabetes to type 2 diabetes, “one might consider a trial of metformin in obese children who have failed to lose weight after diet modification and increased physical activity, especially if there is an elevated fasting glucose on abnormal glucose tolerance on a two-hour oral glucose tolerance test,” he suggested.
“In those situations,” Dr. Kaplowitz concluded, “it may be best to increase the dose of metformin (if there is no GI intolerance) to the maximum recommended dose of 2,000 mg per day to take advantage of the effect of the drug on decreasing appetite.”
Dr. Sophia Yen, an adolescent medicine specialist at Stanford University School of Medicine in Palo Alto, California, told Reuters Health, “It was smart of the researchers to separate the analysis by pre-pubertal versus pubertal stage, because, as they noted, puberty is a known time of insulin resistance.”
Dr. Yen agreed that the lack of effect in adolescents might be due to an insufficient dosage of metformin. “In pediatrics, we generally dose medications according to mg per kg and in this study they did not,” she said by email.
“If you look at the BMI of the prepubertal versus the pubertal you will see that the pubertal are slightly higher, and this would indicate they need more medication,” she noted. The pubertal children also had higher fasting insulin levels; “thus, they might need more metformin.”
Dr. Yen said she treats children with abnormal fasting insulins with metformin, and while it doesn’t cause weight loss, in most patients it does stop weight gain. “Because these are growing children, this results in lowering of the BMI over time, because they maintain their weight as they grow taller.”
Dr. Yen concluded, “Although this study was done on a Spanish population, given the high Hispanic population in the U.S., it is applicable (here). Also, future research needs to be done to see if the response varies by ethnicity.”
Dr. Aguilera did not provide a comment.
SOURCE: http://bit.ly/2sEx1bz
Pediatrics 2017
(c) Copyright Thomson Reuters 2017. Click For Restrictions - http://about.reuters.com/fulllegal.asp