Because type 2 diabetes among children is a relatively recent development, many treatment decisions have relied on what is known about adults with type 2 diabetes. Now, in the first major trial to compare treatments for the disease in young people, researchers have learned that two drugs are better than one for maintaining blood sugar control in these children.
Combined treatment with the diabetes drugs metformin and Avandia proved more effective than metformin alone or metformin plus lifestyle changes for keeping blood sugar at normal levels. Still, the combination failed to help more than a third of patients who took it.
The findings suggest that aggressive and early drug therapy may help children and teens with type 2 diabetes control their blood sugar levels and reduce the risk of complications such as heart disease, kidney failure, blindness, and nerve damage.
They also confirm that for many children with the disease, standard treatment with metformin alone is not enough, says Barbara Linder, MD, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Metformin is the only oral diabetes drug that has been approved by the FDA for use in children.
"These kids did not do as well on metformin as anticipated based on our experience in adults," she tells WebMD. "The assumption has been that kids will do fine on metformin, but clearly that is not the case."
Avandia Use Restricted During Trial
Closely linked to obesity, type 2 diabetes was almost unheard of in children just a few decades ago.
The obesity epidemic has changed this, however, and doctors have made troubling discoveries about early-onset type 2 diabetes, says pediatric endocrinologist and researcher Philip Zeitler, MD, PhD, of the Children's Hospital Colorado.
"We are learning that type 2 diabetes is a more aggressive disease in youth than in adults and progresses more rapidly, which could be why metformin alone has a higher than expected failure rate," Zeitler says.
The finding that adding Avandia to metformin resulted in better outcomes raises more questions than it answers, since Avandia is no longer a treatment option for children and teens, says University of Wisconsin professor of pediatrics David B. Allen, MD.
In September of 2010, while the trial was under way, the FDA placed broad restrictions on Avandia's use following reports of heart attacks and strokes in adults taking the drug.
Participants in the Avandia part of the study continued taking the drug following a safety review, and no serious side effects were reported.
Lifestyle Findings Disappointing
The study, published early in the New England Journal of Medicine, included 699 patients between the ages of 10 and 17 who were diagnosed with type 2 diabetes about eight months before recruitment into the study.
Study participants were randomly split into three treatment groups: treatment with metformin alone, metformin and Avandia together, or metformin plus lifestyle changes designed to promote weight loss.
Over an average follow-up of nearly four years:
- About half the patients who took metformin alone failed the treatment, meaning that they did not achieve adequate blood sugar control for a minimum of two years or ended up requiring insulin.
- 38% of patients who took metformin and Avandia failed treatment.
- 46% of patients in the metformin and lifestyle part of the study failed treatment. A family-based weight management program was found to add little benefit to treatment with metformin alone. While some children in the program lost weight, most did not.
Those taking part in the lifestyle program tended to lose more weight than the other children, but the weight loss did not translate to better blood sugar control.
"We are still trying to understand this, but the findings should not be interpreted as suggesting that lifestyle doesn't matter," Linder says.
In an editorial published along with the study, Allen argues that efforts to teach children to make healthy lifestyle choices are undermined by the environment they live in.
"Fifty years ago, children did not avoid obesity by making healthy choices; they simply lived in an environment that provided fewer calories and included more physical activity for all," he writes. "Until a healthier 'eat less, move more' environment is created for today's children, lifestyle interventions like that in (this) study will fail."
Allen tells WebMD that while it is important to teach kids how to make healthy choices, public health programs that put the responsibility on the children to make the decisions are destined to fail.
"That is just so contradictory to the nature of being a child," he says. "Getting hung up on what drug or combination of drugs results in a few better percentage points of improvement completely misses the point. The big picture is that once kids develop this disease they tend to deteriorate quickly, and the result is decades of poor health."