Metformin Reduces Blood Glucose and BMI in Obese Children

Diedtra Henderson

December 14, 2012

Severely obese children and adolescents who took 1.5 g metformin daily reduced their body mass index SD scores (BMI-SDS) by 3% at 6 months without making significant changes to their diets and physical activity levels.

The results of the randomized, placebo controlled trial, led by Deborah Kendall, MD, from the Department of Pediatric Endocrinology, Royal Manchester Children's Hospital, United Kingdom, were published online November 21 and in the January 2013 issue of the Journal of Clinical Endocrinology & Metabolism.

In the last 2 decades, the number of obese children and youth has soared, as have diagnoses of type 2 diabetes (T2D) and insulin resistance syndrome.

Metformin is known to reduce the risk for T2D in obese adults, but its safety and efficacy in children has been largely unknown. Therefore, Dr. Kendall and coauthors sought to determine whether the medication can benefit obese children by looking at the drug's ability to reduce BMI-SDS. The medicine is not approved for use by obese children or adults in the United Kingdom, but a recent study indicated it has been prescribed for children and youth as an obesity treatment off-label.

The current study, Metformin in Obese Children and Adolescents (MOCA) trial, was a randomized, double-blind, placebo-controlled study conducted at 6 pediatric endocrine centers in the United Kingdom from May 2005 to July 2010. The trial enrolled 151 obese children aged 8 to 18 years who had hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance. Of these participants, 102 (67.5%) were girls, 115 (76.2%) were white, 34 (22.5%) were British Asian, and 2 (1.3%) were Afro-Caribbean. In addition, 89 (58.9%) had a family history of T2D. Study participants were randomly assigned to receive either 1.5 g metformin (74 participants) or 1.5 g placebo (77 participants) daily.

"Metformin was associated with a significant reduction in BMI-SDS," the authors write. "For the 55 participants in each group who contributed to outcome data, mean BMI-SDS changed from +3.44 (SD 0.57) to +3.35 (0.65) in the metformin group, compared with +3.34 (0.5) to +3.31 (0.54) in the placebo group [mean adjusted difference between groups at 6 months was −0.1 SD (95% confidence interval −0.18 to −0.02), P = 0.02]."

Metformin was also associated with lower fasting glucose at 3 months. Fasting glucose dropped from "4.83 (0.46) mmol/liter to 4.79 (0.46) mmol/liter in the metformin group, compared with the placebo group [mean difference: −0.16 mmol/liter (−0.31 to −0.00), P = 0.047]." The authors note, however, that the difference between the 2 groups was not statistically significant at 6 months, even though the drop was maintained.

In addition, there was an improvement in alanine aminotransferase at 3 months, but the benefit was not maintained at 6 months. There were no significant changes in concentrations of adiponectin, resistin, and leptin.

Although the BMI-SDS reduction among the metformin group was small, the authors argue "it is still significant. On an individual level, it may bring to an end the often inexorable rise in BMI that has been an ingrained pattern for many years. The benefits in halting this rise are both physical and psychological and include an increase in an individual's self-esteem and enthusiasm to then make further increased effort with changes in lifestyle."

The treatment appeared safe, with no serious adverse events. Participants in the metformin group, however, reported more adverse events than those in the placebo group (20 vs 8). Most of those adverse events were gastrointestinal issues, which are known adverse effects of metformin in adults.

Study limitations included a 27% dropout rate and difficulties in assessing the participants' compliance with treatment. Although the children were given healthy lifestyle advice at the start of the study, including a sheet with advice on healthy diets, the study lacked a lifestyle-modification group.

"The MOCA trial provides evidence that a short treatment course of metformin is clinically useful, safe, and well tolerated to halt further gain in adiposity and improve fasting glucose, [alanine aminotransferase], and [adiponectin to leptin ratio]," the authors conclude. "Metformin may also provide a stimulus for further lifestyle changes and is a useful adjunct to support lifestyle modification and potentially reduce long-term risk of cardiovascular disease and T2D."

The study was supported by the Central Manchester University Hospitals NHS Foundation Trust and the Child Growth Foundation U.K. The study authors disclosed no relevant financial conflicts.

J Clin Endocrinol Metabol. Published online November 21, 2012. Abstract