Effect of Metformin in Pediatric Patients With Type 2 Diabetes

Effect of Metformin in Pediatric Patients With Type 2 Diabetes A randomized controlled trial Kenneth Lee Jones , MD 1 , Silva Arslanian , MD 2 , Valentina A. Peterokova , Prof 3 , Jong-Soon Park , PHD 4 and Mark J. Tomlinson , MD 4 1 University of California, San Diego Medical Center, San Diego, California 2 Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 3 National Endocrinology Research Center, Russian Academy of Medical Sciences, Moscow, Russia 4 Bristol-Myers Squibb, Princeton, New Jersey Abstract OBJECTIVE —Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes. RESEARCH DESIGN AND METHODS —This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10–16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels ≥7.0 and ≤13.3 mmol/l (≥126 and ≤240 mg/dl), HbA 1c ≥7.0%, stimulated C-peptide ≥0.5 nmol/l (≥1.5 ng/ml), and a BMI >50th percentile for age. RESULTS —Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was −2.4 mmol/l (−42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo ( P < 0.001). Mean HbA 1c values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin. CONCLUSION —Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients. ADA, American Diabetes Association ANCOVA, analysis of covariance DSMB, Data and Safety Monitoring Board FPG, fasting plasma glucose; Footnotes Address correspondence and reprint requests to Kenneth Lee Jones, University of California, San Diego, Division of Endocrinology and Diabetes, 9500 Gilman Dr., #0831, La Jolla, CA 92093. E-mail: kljones{at}ucsd.edu . Received for publication 12 April 2001 and accepted in revised form 22 Aug