A combination of the diabetes staple drug metformin plus Avandia is best at controlling blood sugar in children and adolescents with type 2 diabetes, researchers found.
The combination was superior to monotherapy with metformin, even though the use of Avandia has fallen off in the U.S. and Europe given concerns about cardiovascular side effects with the thiazolidinedione (TZD) class in adults, Kathryn Hirst of George Washington University in Washington, and colleagues reported in the New England Journal of Medicine.
"Monotherapy with metformin is not adequate in many kids, and combination therapy appears to bring benefits," Dr. Phil Zeitler, of the University of Colorado Denver and a co-author on the paper, 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."
Read this story on www.medpagetoday.com.
Adding a lifestyle intervention to metformin didn't offer any additional benefits beyond metformin alone, the researchers found, nor did its effects differ significantly from those of metformin and Avandia combination therapy.
In an accompanying editorial, Dr. David Allen, 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 percent of those on metformin alone, 39 percent of those on combination drug therapy, and 47 percent of those in the metformin plus lifestyle intervention group had treatment failure during a mean follow up of about four 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 gone hand-in-hand with increases in childhood obesity. Yet there are few data to guide treatment of the condition in young people, the researchers said. So 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 about eight months.
Patients were randomized to metformin alone (1,000 mg twice a day), metformin plus Avandia (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 another class of diabetes drug, sulfonylureas, had been found to cause unacceptable levels of hypoglycemia in young patients, and 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 last few months of the trial "based on the lack of evidence of safety concerns in the study identified by our data safety monitoring board."
The lifestyle program was developed specifically for the study, involved several components based on the best available evidence, and was delivered by trained personnel.
The primary endpoint was achieving and maintaining an HbA1c level of less than 8 percent.
Hirst and colleagues found that about 45 percent of the entire study population achieved those levels during a mean follow up of 3.86 years.