NIH-funded study: Early, intensive treatment may be needed for some youth with type 2 diabetes

Youth with type 2 diabetes who do not get their blood glucose levels into a nondiabetic range using metformin alone tend to quickly advance to higher blood glucose levels, according to the latest findings of the Treatment Options for Type 2 Diabetes in Youth study (TODAY). Results of the study, funded largely by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, were published online Nov. 4, 2015, in Diabetes Care.

Once rare, type 2 diabetes has risen in youth along with the rise in childhood obesity. To determine how best to treat this population, the TODAY study enrolled 699 youth who had type 2 diabetes for less than two years and a body mass index (BMI) at the 85th percentile or greater.

The TODAY researchers had measured participants’ blood glucose levels through the A1C test, which measures a person’s average levels of blood glucose over a three-month period. Typically, a person without diabetes or prediabetes should have an A1C measure below 5.7 percent, while people with diabetes often aim for an A1C below 7 percent.

The TODAY study found that almost half of participants were unable to achieve and sustain glucose control below 8 percent on metformin alone. Metformin is generally accepted as the first drug to be used in the treatment of type 2 diabetes. After examining the results, investigators wanted to understand if they could predict which youth were able to achieve good glucose control on metformin by looking at the data already collected.

Researchers found that, in the TODAY study participants, an A1C greater than 6.3 percent shortly after beginning treatment with metformin could predict loss of blood glucose control and a need for more aggressive intervention.

“The results show that we may be looking at two distinct populations of youth with type 2 diabetes, each potentially needing a different course of treatment,” said Barbara Linder, M.D., Ph.D., project scientist for TODAY and NIDDK senior advisor for childhood diabetes research. “The group with an A1C greater than 6.3 percent saw their glucose levels go up dramatically over a short time, a sign that they likely need close monitoring by their healthcare teams, even if blood glucose is in a range normally acceptable for their adult counterparts with type 2.”

The researchers speculate that the difference in treatment response may be due to genetic differences in the groups, where one genetic type leads to more rapid loss of beta cell function. Beta cells make the blood glucose-regulating hormone insulin.

As the study was not designed specifically to test whether tighter blood glucose control would improve the health of youth with type 2 diabetes, additional studies should be done to confirm these findings.

TODAY participants were randomly assigned to one of three treatment groups: metformin alone, metformin and rosiglitazone together, and metformin plus intensive lifestyle changes aimed at helping participants lose weight and increase physical activity.

In 2011, primary results of the study showed two drugs in combination – metformin and rosiglitazone – were more effective than metformin alone. The researchers noted that the high rate of poor  glucose control with metformin alone in TODAY youth was unexpected,  compared to its reported effectiveness in adults with type 2 diabetes. Later findings showed that youth with type 2 diabetes tend to progress more rapidly than adults toward early signs of developing heart, kidney and eye complications.

In addition to support from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK061212, U01DK61230, U01DK061239, U01DK061242 and U01DK061254) and the National Center for Research Resources, the TODAY study received support from BD, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, LifeScan Inc., Pfizer Inc., and Sanofi-aventis.

Media contact information: niddkmedia@niddk.nih.gov or (301) 496-3583.