Young patients with type 2 diabetes achieved glycemic control by taking a combination of metformin and rosiglitazone, according to data from a major comparative effectiveness trial.
“Metformin alone was effective in maintaining durable glycemic control in only half the study participants, and the addition of rosiglitazone, but not intensive lifestyle intervention, was superior to metformin alone,” the researchers wrote.
Phil Zeitler, MD, pediatric endocrinologist at Children’s Hospital Colorado and study chair of the Treatment Options for Type 2 Diabetes in Youth (TODAY) trial, and colleagues designed a multicenter, randomized clinical trial in which they compared metformin alone with two other treatment approaches — combined metformin with rosiglitazone (Avandia, GlaxoSmithKline), and combined metformin with an intensive lifestyle-intervention program.
The trial objective was to test the hypothesis that combination therapy started early in a young person with onset type 2 diabetes would result in acceptable glycemic control, rather than treatment with metformin alone.
“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,” Zeitler said in a press release. “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 study included 699 patients aged 10 to 17 years who were randomly assigned to one of three treatment groups: metformin 1,000 mg twice daily alone, metformin 1,000 mg twice daily plus rosiglitazone 4 mg twice daily or metformin plus a lifestyle-intervention program. The average onset of type 2 diabetes diagnosis was 7.8 months, the researchers wrote, and patients were followed for 3.86 years.
Almost 50% of patients (45.6%) reached the anticipated outcome of glycemic stability. The failure rate was 51.7% with metformin alone (95% CI, 45.3-58.2; 120 of 232 patients), 38.6% (95% CI, 32.4-44.9; 90 of 233 patients) with metformin plus rosiglitazone and 46.5% (95% CI, 40.2-53; 109 of 234 patients) with metformin plus lifestyle intervention. However, overall failure rates were 44.3% among girls and 48.2% among boys, the researchers wrote.
In September 2001, the FDA restricted the use of rosiglitazone in the United States and Europe because of studies demonstrating a link between treatment and a high risk for myocardial infarction and stroke in adults. Serious adverse events related to this study were reported in 19.2% patients.
Disclosure: Dr. Zeitler has received consultancy fees from Bristol-Myers Squibb, Merck and Sanofi-Aventis. Other study researchers report financial ties with: Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, DPS Health, Jenny Craig/Nestle, Medtronic, Novo Nordisk, Sanofi-Aventis, Shire and United Health Group. In addition, Dr. Zeitler and colleagues have received grants to their institutions from NIDDK/NIH, with some money used to fund travel for this study.