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TODAY study results suggest new treatment options for youth with diabetes
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PHILADELPHIA — Children diagnosed with type 2 diabetes appear to experience a more rapidly progressive disease than people who are diagnosed as adults, with a higher rate of early complications and a relatively early need for combination therapy or insulin, according to results from the large, longitudinal TODAY study.
Initial results
The Treatment Options for Type 2 Diabetes in Youth (TODAY) study included 699 youth with type 2 diabetes aged 10 to 17 years across 15 health centers in the United States. All patients were initially treated with metformin and then randomly assigned to one of three treatment arms:
- metformin 1,000 mg twice daily alone;
- metformin 1,000 mg twice daily plus rosiglitazone 4 mg twice daily; or
- metformin 1000 mg twice daily plus a lifestyle intervention program.
Initial results were published in The New England Journal of Medicine in late April. Researchers found no difference in outcomes between the metformin-only (rate of failure 51.7%) and metformin plus intensive lifestyle change (46.6%) groups. However, combining metformin and rosiglitazone was superior (38.6%) to metformin only.
“Given the current restrictions on the marketing and use of rosiglitazone in the United States and Europe, and the current concerns about the safety of rosiglitazone, we are not recommending rosiglitazone be used in these children,” Philip S. Zeitler, MD, PhD, study chair and pediatric endocrinologist at Children’s Hospital Colorado, said during a presentation at the American Diabetes Association’s 72nd Scientific Sessions.
“The nature of what this second agent needs to be obviously requires further study. However, these results suggest that combination therapy will be something that we need to look at very carefully,” Zeitler added.
New analyses
Kenneth Copeland, MD, of the department of pediatrics at University of Oklahoma Health Sciences Center and vice-chair of the TODAY study, presented new data from an analysis that compared characteristics of those participants who maintained long-term durable glycemic control (for at least 4 years) with those whose treatment failed before 4 years.
Several variables obtained before randomization predicted failure, including a higher BMI (P<.0001), depression (P=.0217), race (black patients compared with white patients; P=.0323), a higher HbA1C (P<.0001), and a lower ability to secrete insulin (indicated by the insulinogenic index; P<.0001), although when analyzed in a multivariate model, only HbA1C (P<.0001) and insulin secretion (P=.0498) remained significant predictors.
Changes in measures over time for predicting failure also were considered. Although higher BMI and lower insulin secretion at baseline were predictive of failure, changes over time for either variable were not, with BMI increasing at similar rates and insulin secretion falling at similar rates in both groups. The only factor that predicted failure over time in the study was HbA1C, with values in the group that failed being both higher at baseline and increasing more rapidly during the study (P<.0001).
Copeland added that the mean HbA1c values before randomization of those who maintained durable glycemic control (5.7%) and of those who failed (6.4%), even though significantly different from each other, both had been in the non-diabetic range.
There was no difference related to insulin sensitivity (indicated by the inverse of the fasting insulin level), either at baseline or change throughout the study in predicting failure, with insulin sensitivity improving during treatment in both groups.
Focus of future investigations
The TODAY study results emphasize the need for new treatments for youth by revealing the high rate of comorbidities that manifest within a relatively short duration of living with the disease, according to the researchers. Nearly one-third of the children in the study exhibited hypertension by the end of the study’s mean follow-up of nearly 4 years, compared with just 12% at the beginning of the study, and close to 17% exhibited elevated urinary albumin levels, up from 6% at the beginning of the study, according to a press release. About 13% of those in the study exhibited signs of retinopathy, “which is relatively high after such as short duration of disease,” Lori Laffel, MD, MPH, chief of the pediatric, adolescent and young adult section at Joslin Diabetes Center and a TODAY study co-investigator, said in the release.
“The biggest concern with diabetes is the consequences in terms of CVD and microvascular disease and these kids are at very high risk at young ages,” Zeitler stated in the release. “Within the next 10 to 20 years, many of these kids will have substantial health problems. This suggests a major health burden in the future.” – by Samantha Costa
For more information:
TODAY Study Group. N Engl J Med. 2012;doi:10.1056/NEJMoa1109333.
Zeitler P. Treatment and clinical course of recent-onset type 2 diabetes in youth — Data from the TODAY trial. Presented at: the American Diabetes Association’s 72nd Scientific Sessions; June 8-12, 2012; Philadelphia.
Disclosure: Dr. Zeitler reported ties to Bristol-Myers Squibb, Merck and Sanofi-Aventis. Other study researchers report financial ties with: Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, DPS Health, Jenny Craig/Nestle, Medtronic, Novo Nordisk, Sanofi-Aventis, Shire and United Health Group.