Combo Tx Checks Blood Sugar in Diabetic Kids

Metformin and rosiglitazone together are best at controlling blood sugar in children and adolescents with type 2 diabetes, researchers found.

The combination was superior to monotherapy with metformin (P=0.006), even though the use of rosiglitazone (Avandia) has fallen off in the U.S. and Europe because of concerns about cardiovascular side effects with thiazolidinedione (TZD) in adults, reported Kathryn Hirst, PhD, of George Washington University in Washington. and colleagues in the New England Journal of Medicine.

"Monotherapy with metformin is not adequate in many kids, and combination therapy appears to bring benefits," co-author Phil Zeitler, MD, of the University of Colorado in Denver, told MedPage Today in an email. "The challenge now is to determine what that combination therapy should look like given that thiazolidinediones are not a good option."

Adding a lifestyle intervention to metformin didn't offer any additional benefits beyond metformin alone, the researchers also found, nor did its effects differ significantly from those of metformin and rosiglitazone combination therapy.

In an accompanying editorial, David Allen, MD, of the University of Wisconsin in Madison, called the overall findings of the trial "discouraging" because of the high rates of treatment failure across all three groups.

Indeed, about 52% of those on metformin monotherapy, 39% of those on combination drug therapy, and 47% of those in the metformin plus lifestyle intervention group had treatment failure during a mean follow up of about 4 years.

"These data imply that most youth with type 2 diabetes will require multiple oral agents or insulin therapy within a few years of diagnosis," Allen wrote.

The rise in type 2 diabetes among American youth has increased with the incidence of childhood obesity. Yet there are few data to guide treatment of the condition in young people, the researchers said.

They conducted the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study in 699 patients, ages 10 to 17, who'd had diabetes for a mean of 7.8 months.

Patients were randomized to metformin alone (1,000 mg twice a day), metformin plus rosiglitazone (4 mg twice a day), or to metformin plus a lifestyle intervention focused on weight loss.

Zeitler said the study was designed in 2002, before concerns about the TZD class had arisen, and rosiglitazone "was a logical choice" at the time, particularly because sulfonylureas had been found to cause unacceptable levels of hypoglycemia in young patients. In addition, few of the other oral drugs commonly used today, including DPP-4 inhibitors and GLP-1 agonists, were available.

He added that the study was wrapping up as the FDA put restrictions on the drug, but the agency gave his group the go-ahead to finish the trial based on a lack of evidence of safety concerns.