SAN FRANCISCO — Metformin is associated with modest weight loss and some improvements in signs of metabolic syndrome in obese children with severe hyperinsulinemia, a government-sponsored randomized controlled trial has concluded.
But because this is the first such study in children, the drug can't yet be recommended for routine use in this population, Dr. Jack Yanovski said at the annual meeting of the Endocrine Society.
Dr. Yanovski, chief of the National Institutes of Child Health and Human Development's Unit on Growth and Obesity, presented the results of the first placebo-controlled trial of metformin in children aged 6–12 years. The 100 children who participated (mean age 10 years) were all obese (mean body mass index [BMI] 34.6 kg/m
The cohort consisted mostly of female children (60%). Children randomized to metformin (53) were started at 1,000 mg/day; this was ramped up to a final dosage of 1,000 mg twice a day for the duration of the 6-month trial. All children but one were able to tolerate the dose. All children also took a daily multivitamin supplement.
By the study's end, mean BMI had decreased in the active group and increased in the placebo group (−1 kg/m
Some signs of metabolic syndrome improved in children taking metformin, although the changes were not significant. Serum glucose, homeostatic assessment model algorithm (HOMA) insulin resistance index, and total cholesterol all improved in the treated children.
Children in the metformin group experienced a significant decrease in serum vitamin B12 concentrations, although all remained within normal range, and no child required additional supplementation.
The most commonly reported adverse events were liquid stool (60% metformin vs. 2.5% placebo), nausea (24% vs. 8%), and fatigue (14% vs. 5%). All were significantly more common in the metformin group; however, by the study's end, the incidence of liquid stool had decreased by 20% and the incidence of nausea had decreased by 8%.
Metformin also appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake, according to a substudy of the same government-sponsored trial, Rachael Sorg said in a poster session at the Endocrine Society meeting.
Some of the children (45 metformin-treated and 39 placebo-treated) participated in both a pre- and posttreatment meal study to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced, and one at the end of the 6-month treatment period.
Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.
Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.
Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake. They also reported significantly decreased feelings of hunger and increased feelings of fullness after the shake. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.
“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.
Dr. Yanovski and Ms. Sorg said they had no financial disclosures to make with regard to metformin.
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