Children who received at least 274 mg of metformin for any reason grew about 1 cm more than controls, authors of a meta-analysis reported online in JAMA Pediatrics.
The relative increase “may appear small, [but] is likely underestimated, given that many studies were of short duration and included older adolescents, potentially after epiphyseal growth plate closure,” wrote Nicholas Kuzik of the University of Alberta in Edmonton, Canada, and his associates. “It is possible that longer treatment periods or treatments concentrated at times of greater growth may lead to even greater height changes,” the researchers added.
Metformin has been increasingly used off label for children and adolescents who have impaired glucose tolerance, nonalcoholic fatty liver disease, obesity, or polycystic ovary syndrome, the investigators noted. Their meta-analysis included 10 randomized controlled trials of 562 such patients who were 8 to almost 16 years old. A total of 59% of children were female and body mass index ranged from 18.4 to 41 (JAMA Pediatr. 2015 Sept. 28. doi: 10.1001/jamapediatrics.2015.2186).
Height gains did not statistically differ between groups when the researchers analyzed all 10 studies together. The 1-cm greater average increase with metformin, compared with controls (95% confidence interval, 0.0 to 2.0 cm) applied only to the five studies that used the highest cumulative doses of at least 274 mg. Metformin conferred no relative gains in height for the five trials that used lower cumulative doses of 91-186 mg. The lower-dose studies also involved 3-6 months of treatment, compared with 6-48 months for the high-dose trials, said Mr. Kuzik and his associates.
Metformin affects several factors that mediate growth, including sex hormones, insulin or insulin-like growth factor 1, and adenosine monophosphate–activated protein kinase, the investigators noted. They recommended longer-term studies of younger children.
The investigators declared no funding sources or competing interests.