A Clinical Trial to Maintain Glycemic Control in Youth With Type 2 Diabetes

Study Questions:

What is 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 <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 ≥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:

The authors concluded that monotherapy with metformin was associated with durable glycemic control in approximately one half of children and adolescents with type 2 diabetes.

Perspective:

This study reports that metformin monotherapy provided durable glycemic control in only one half of the participants, and that the combination of metformin and rosiglitazone improved the durability of glycemic control. Furthermore, metformin combined with lifestyle intervention was no better than metformin alone in maintaining glycemic control. Whether the effect shown in this study is specific for rosiglitazone, a more general effect of thiazolidinediones, or a feature of combination therapy is unclear. Also, while further analysis of the effect of various components of the lifestyle intervention is needed to understand the current findings, we need to identify ways to effectively integrate lifestyle intervention in the ongoing care of every youth with type 2 diabetes. Overall, the results suggest that a majority of youth with type 2 diabetes may require combination treatment or insulin therapy within a few years after diagnosis.

Keywords: Hemoglobin A, Glycosylated, Drug Combinations, Insulin, Weight Loss, Blood Glucose, Metformin, Diabetes Mellitus, Type 2, Thiazoles, Hispanic Americans, Thiazolidinediones


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