A clinical trial to maintain glycemic control in youth with type 2 diabetes

Abstract

Background: Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes.

Methods: Eligible patients 10 to 17 years of age were treated with metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin.

Results: Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P=0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants.

Conclusions: Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.).

Figure 1. Enrollment, Randomization, and Retention of the Study Participants

All randomly assigned participants were included in the primary outcome analysis (i.e., all participants contributed time in the study, although data for some participants were censored before the end of the study for the reasons shown in the figure).

Figure 2. Overall Primary Outcome Results

Survival curves for freedom from glycemic failure are shown. Data are shown for up to 60 months of follow-up (accounting for 98.4% of cases of glycemic failure), although the rates and analysis are based on the complete data set.

Figure 3. Primary Outcome Results According to Sex and Race or Ethnic Group

Survival curves for freedom from glycemic failure are shown. Data are shown for up to 60 months of follow-up (accounting for 98.4% of cases of glycemic failures), although the rates and analysis are based on the complete data set.