Adolescents with obesity and insulin resistance assigned to metformin therapy saw an initial decrease in BMI during the first 6 to 9 months of treatment before returning to baseline levels, whereas those assigned a placebo experienced a steady increase in BMI, according to recent study results.
“In our study, where we report on treatment effects after 18 months, the difference between metformin and placebo remained significant, even though it seems that BMI values return to baseline in the metformin group,” Marloes P. van der Aa, MD, of the department of pediatrics at St. Antonius Hospital in Nieuwegein, Netherlands, and colleagues wrote. “An intriguing question is, therefore, how BMI will change over time after these 18 months.”
Van der Aa and colleagues randomly assigned children aged 10 to 16 years with obesity and insulin resistance to 2,000 mg daily metformin (n = 23; mean age, 14 years; six boys; mean baseline BMI, 29.8 kg/m²) or placebo (n = 19; mean age, 12 years; eight boys; mean baseline BMI, 30.5 kg/m²) daily along with physical training twice weekly and monthly phone calls for 18 months. Primary endpoints were change in BMI and insulin resistance measured by homeostasis model assessment for insulin resistance (HOMA-IR); secondary endpoints included safety and tolerability of metformin, body fat percentage and change in HbA1c.
At 18 months, participants assigned metformin therapy saw a mean BMI increase of 0.2 kg/m² (95% CI, –2.9 to 1.3) vs. 1.2 kg/m² in the placebo group (95% CI, –0.3 to 2.4). Researchers attributed the between-group difference to a BMI decrease during the first 6 to 9 months in the metformin group, followed by a return to baseline values; the trend was not observed in the placebo group.
There were no between-group differences related to HOMA-IR. Two patients in the metformin group discontinued treatment due to adverse gastrointestinal events; four participants did not tolerate the maximum 2,000-mg dose. Metformin participants reported more nausea overall (73.9%) than those assigned placebo (42.1%).
Mean HbA1c increased in both groups, with a larger increase observed in the placebo group (P = .02). Participants assigned metformin saw a decrease in fat mass during the study period, whereas participants assigned placebo saw a gain in fat mass (P = .007). Researchers observed no between-group differences for quality-of-life measures.
“Long-term treatment with metformin in adolescents with obesity and insulin resistance results in a stabilization of BMI and improved body composition compared with placebo,” the researchers wrote. “Therefore, metformin may be considered a safe additional therapy in combination with lifestyle intervention.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.