Metformin and Rosiglitazone in Youth with Type 2 Diabetes

A study of youth with type 2 diabetes found that combination treatment with metformin and rosiglitazone was superior to metformin alone in providing durable glycemic control. The results of the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study were recently reported online in the New England Journal of Medicine [10.1056/NEJMoa11093333].

Researchers conducted the study to gain more insight into treatment options and effectiveness for the rising number of youth with type 2 diabetes. According to the study, maintaining glycemic control as an adolescent may help prevent microvascular and macrovascular complications that are often related to duration of the disease and lack of glycemic control developing later in adulthood.

In this randomized trial, researchers assessed 3 treatment options in multiple centers for youth 10 to 17 years of age who had type 2 diabetes based on American Diabetes Association criteria for <2 years. Participants also had a body mass index (BMI) ≥85th percentile for age and sex, a negative test for diabetes-related autoantibodies, a fasting c-peptide level of >0.6 ng per milliliter, and parental support.

Participants in the TODAY study were randomized to receive either (1) metformin given alone at a dose of 1000 mg twice a day, (2) metformin and 4 mg of rosiglitazone twice a day, or (3) metformin and a lifestyle-intervention program, which focused on weight loss through family changes to diet and activity. The lifestyle-intervention program also included a series of in-person visits during the first 2 years and quarterly medical visits.

The mean follow-up time of the study was 3.8 years.

Researchers identified the primary outcome as the loss of glycemic control, which occurred in the study when glycated hemoglobin levels were at least 8% for 6 months or if there was sustained metabolic decomposition that required insulin. Participants had their glycated hemoglobin level tested every 2 months in the initial year and quarterly in the subsequent years of the study.

According to the study's findings, of the 699 participants included in the study, 45.6% reached the primary outcome with a median time to treatment failure of 11.5 months (range <1 to 66).

The participants who received combination therapy of metformin and rosiglitazone had significantly lower treatment failure, with 38.6% (95% confidence interval [CI], 32.4-44.9; 90/233 participants) of participants losing glycemic control. The treatment failure rate for the metformin plus lifestyle intervention was 46.6% (95% CI, 40.2-53.0; 109/234 participants), while those in the group receiving metformin alone experienced the highest treatment failure rate of 51.7% (95% CI, 45.3-58.2; 120/232 participants). Researchers reported that metformin plus rosiglitazone was superior to metformin alone (P=.006); however, the difference between metformin plus the lifestyle intervention and metformin alone failed to reach significance.

Although the combination therapy group had the lowest treatment failure, they also had the highest increase in BMI. Participants in the combination drug therapy regimen saw an average change in percent overweight at 6 months of 0.81 percentage points, whereas the group taking metformin alone saw a change of –1.42 percentage points and the group taking metformin and participating in the lifestyle intervention saw a change of –3.64.

When researchers conducted subgroup analyses of their data, they found that there were differences in effectiveness between subgroups in the study. For instance, the combination drug therapy was most effective in girls rather than boys (P=.03), while metformin alone was reported to be the least effective in non-Hispanic African Americans.