According to a study(www.nejm.org) recently published in the New England Journal of Medicine, children and adolescents with type 2 diabetes may be compelled to begin combination therapy or insulin injections sooner than expected.
Using data from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)(clinicaltrials.gov) multicenter, randomized clinical trial, the authors of the April 29 article found that monotherapy with metformin was associated with durable glycemic control in only about half of children and adolescents with type 2 diabetes who participated in the trial, whereas the addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone.
"These results suggest that a majority of youth with type 2 diabetes may require combination treatment or insulin therapy within a few years after diagnosis," the researchers wrote.
The study randomly assigned 699 young people (ages 10-17 years) with type 2 diabetes to test how well metformin alone, metformin plus rosiglitazone, and metformin plus an intensive lifestyle-intervention program maintained glycemic control (a glycated hemoglobin level of less than 8 percent) for a minimum of two years.
- A study recently published in the New England Journal of Medicine suggested that children and adolescents with type 2 diabetes may require combination therapy or a move to insulin injections only a few years after diagnosis.
- Metformin, used in combination with the restricted-access drug rosiglitazone, was more effective in controlling sugar levels than either metformin alone or metformin in combination with an intensive lifestyle intervention program.
- The lifestyle intervention program did not significantly improve glycemic control and helped less than one-third of participants achieve the targeted weight loss goal.
Study results indicated that 52 percent of participants treated with metformin alone experienced treatment failure, which is a higher failure rate than in recently diagnosed adult patients, although the definition of failure varies among clinical trials. The metformin-plus-lifestyle-intervention option not only failed to significantly improve glycemic control, it achieved the secondarily targeted weight loss in only 31 percent of the treatment group. In addition, this weight loss appeared to be transitory in many of the participants. Lastly, although the addition of rosiglitazone to metformin improved durable glycemic control, 39 percent of the group was classified as having failed treatment.
Treatment failure was defined as a persistently elevated glycated hemoglobin level (i.e., 8 percent or greater) spanning a period of six months or persistent metabolic decompensation (defined as either the inability to wean the participant from insulin within three months after its initiation for decompensation or the occurrence of a second episode of decompensation within three months after discontinuation of insulin).
Although the combination of rosiglitazone and metformin did reduce the rate of treatment failure when compared with metformin alone -- despite a small increase in body mass index and fat mass in the rosiglitazone-treated participants -- the authors cautioned that more study is needed to determine whether the effect is specific to rosiglitazone, can be more generally applied to all thiazolidinediones, or is a feature of the combination therapy itself.
At present, use of rosiglitazone is restricted in both the United States and Europe(www.ema.europa.eu) because of adverse side effects observed in patients using the drug. However, the study's authors pointed out that none of rosiglitazone's known ill effects -- including an elevated risk for cardiovascular events (e.g., myocardial infarction, stroke) and a negative effect on bone density, which they would have expected to see in this relatively young patient cohort -- presented in this trial.
In a commentary(www.nejm.org) published alongside the study, pediatrician David Allen, M.D., from the University of Wisconsin School of Medicine and Public Health in Madison, said that although the TODAY trial's recruitment and retention of demographically representative children and adolescents and implementation of a lifestyle-intervention program in these study participants represented "an impressive effort," the results were "discouraging."
Even so, Allen suggested that the results of the TODAY study do not "put a nail in the coffin of lifestyle modification and endorse add-on drugs to treat type 2 diabetes in children" so much as they call for society to realize that these children are "immersed from a young age in a sedentary, calorie-laden environment that may well have induced and now aggravates their type 2 diabetes."
"For a substantial proportion of those millions of children at risk for largely preventable type 2 diabetes, the findings of the TODAY study reinforce the idea that medications and even procedures will not stave off a lifetime of illness," Allen wrote. "Furthermore, lifestyle changes for youth are undermined by immersion in an obesogenic world, in which personal responsibility appears to be invalidated by the limits of willpower with respect to overnutrition.
"The stark message from the TODAY study is that, tomorrow and beyond, public policy approaches -- sufficient economic incentives to produce and purchase healthy foods and to build safe environments that require physical movement -- and not simply the prescription of more and better pills, will be necessary to stem the epidemic of type 2 diabetes and its associated morbidity."