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.)

Age-Related Consequences of Childhood Obesity

“…This rapid decline in β-cell function makes the treatment of the increasing number of children diagnosed with T2D more difficult than in adults. For example, children have greater failure rates than adults when using oral therapy with metformin alone, making them more likely than adults to require insulin-based treatment [35]. Being diagnosed with T2D as a child also increases the chance of developing other complications early in life.…”

Type 2 diabetes mellitus in children and adolescents

“…No oral agent should be used during pregnancy. The use of rosiglitazone has been studied in a randomized trial in adolescents compared to lifestyle intervention and metformin in the TO-DAY study [63] : Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes mellitus. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone.…”

Efficacy and Safety of Canagliflozin in Patients With Type 2 Diabetes Mellitus of Different Ethnicity

“…12 Differences in metabolic responses to glucose-lowering agents (eg, insulin, metformin, dipeptidyl peptidase-4 inhibitors) have been observed across racial and ethnic groups. [13][14][15] Most currently available therapies for T2DM have an insulin-dependent mode of action. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drugs that treat T2DM through an insulin-independent mechcently included in the American Diabetes Association (ADA) Standards of Medical Care as an additional treatment option for T2DM to be used as second-or third-line therapy.…”