AURORA, Colo. - A new study has found that a combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study is the first major comparative effectiveness trial for the treatment of type 2 diabetes in young people.
Type 2 diabetes in adults and children is closely linked to being overweight, inactive, and having a family history of diabetes. Type 2 diabetes represents 95 percent of diabetes cases in adults, but is much less common in children than type 1 diabetes.
The childhood obesity epidemic has led to the emergence of type 2 diabetes in youth. However, because type 2 diabetes has been primarily an adult illness, information about how to effectively treat youth is limited, and pediatric diabetes experts have had to rely on what is known about adult treatment.
The TODAY study tested how well and for how long each of three treatment approaches controlled blood glucose levels in youth enrolled from ages 10 to 17 with type 2 diabetes. Participants were randomly assigned to one of three treatment groups: metformin alone, metformin and rosiglitazone together, and metformin plus intensive lifestyle changes aimed at helping participants lose weight and increase physical activity. Currently, metformin is the standard treatment for young people with type 2 diabetes and the only oral drug approved for this use by the U.S. Food and Drug Administration.
The study found that metformin had a much higher failure rate in study participants than has been reported in studies with adults treated with metformin, meaning that control of glucose was lost and insulin was required. Adding a second medication, rosiglitazone, increased the number of youth who were able to maintain control of glucose and reduced the requirement for insulin. However, while studies have shown lifestyle-change programs to be effective in improving blood glucose control for adults with type 2 diabetes, the TODAY lifestyle intervention—a family-based weight-management program that included intensive education and activities delivered one-on-one by trained study staff—added no benefit to the metformin therapy for control of glucose. Youth receiving the lifestyle intervention lost weight, but this was not translated into better diabetes control.
“The results of this study tell us it might be good to start with a more aggressive drug treatment approach in youth with type 2 diabetes,” said Philip Zeitler, MD, PhD, the TODAY study chair and a pediatric endocrinologist at Children’s Hospital Colorado, Aurora and professor of pediatrics and clinical science at the CU School of Medicine. “We are learning that type 2 diabetes is a more aggressive disease in youth than in adults and progresses more rapidly, which could be why metformin alone had a higher than expected failure rate.” The longer a person has type 2 diabetes, the greater the likelihood of developing complications including heart disease, stroke, kidney and eye disease, and nerve damage, making it critical for young people with type 2 diabetes to quickly achieve and sustain control of their blood glucose.
In September 2010, the FDA restricted the use of rosiglitazone because of studies linking the medicine to a higher risk of heart attacks and stroke in adults. The TODAY Data Safety and Monitoring Board—an independent group of health and science experts—carefully examined all safety data for TODAY participants and recommended that the study should continue to test rosiglitazone. Rosiglitazone is sold commercially as Avandia.
TODAY was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part the National Institutes of Health (NIH). The TODAY study took place between 2004 and 2010 at 15 centers across the country, including Children's Hospital Colorado. Study results appear in the New England Journal of Medicine.