Effect of Metformin in Pediatric Patients With Type 2 Diabetes
Effect of Metformin in Pediatric Patients With Type 2 Diabetes
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 1016 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.
The incidence of type 2 diabetes in children has increased dramatically over the past 10 years. This increase has been linked to increasing prevalence of obesity and progressively sedentary lifestyle in American children . Insulin, the only FDA approved medication for the treatment of diabetes in children, is the current standard of care, despite its parenteral route of delivery and association with the side effects of weight gain and hypoglycemia. Children with type 2 diabetes need alternative therapies that improve glycemic control, facilitate administration and compliance, do not promote weight gain, and address comorbid conditions.
Metformin hydrochloride is an oral antihyperglycemic agent that has been used in many countries for >40 years, and it has been marketed in the U.S. for the treatment of adult type 2 diabetes since 1995. Metformin improves glycemic control by reducing hepatic glucose production, increasing insulin sensitivity, and reducing intestinal glucose absorption, without increasing insulin secretion . In adults, metformin is effective as an initial monotherapy to improve glycemia, with a low risk of hypoglycemia, and with potential independent benefits of a lack of weight gain and improved lipid profile .
The phenotypic constellation of type 2 diabetes (hyperglycemia, obesity, dyslipidemia, and insulin resistance) is similar in adults and children . Therefore, it has been reasonable to presume that the pharmacodynamic response to metformin therapy in children would be similar to that documented in adults. This randomized placebo-controlled study was designed to investigate, in a rigorous clinical trial, the safety and efficacy of using metformin for the treatment of children with type 2 diabetes.
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 1016 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.
The incidence of type 2 diabetes in children has increased dramatically over the past 10 years. This increase has been linked to increasing prevalence of obesity and progressively sedentary lifestyle in American children . Insulin, the only FDA approved medication for the treatment of diabetes in children, is the current standard of care, despite its parenteral route of delivery and association with the side effects of weight gain and hypoglycemia. Children with type 2 diabetes need alternative therapies that improve glycemic control, facilitate administration and compliance, do not promote weight gain, and address comorbid conditions.
Metformin hydrochloride is an oral antihyperglycemic agent that has been used in many countries for >40 years, and it has been marketed in the U.S. for the treatment of adult type 2 diabetes since 1995. Metformin improves glycemic control by reducing hepatic glucose production, increasing insulin sensitivity, and reducing intestinal glucose absorption, without increasing insulin secretion . In adults, metformin is effective as an initial monotherapy to improve glycemia, with a low risk of hypoglycemia, and with potential independent benefits of a lack of weight gain and improved lipid profile .
The phenotypic constellation of type 2 diabetes (hyperglycemia, obesity, dyslipidemia, and insulin resistance) is similar in adults and children . Therefore, it has been reasonable to presume that the pharmacodynamic response to metformin therapy in children would be similar to that documented in adults. This randomized placebo-controlled study was designed to investigate, in a rigorous clinical trial, the safety and efficacy of using metformin for the treatment of children with type 2 diabetes.
