Liraglutide once daily is substantially better at controlling blood glucose in type 2 diabetes than is twice-daily exenatide (Byetta from Eli Lilly), according to the LEAD-6 study reported online June 8 in Lancet, and simultaneously presented at the American Diabetes Association (ADA) annual meeting in New Orleans.
Liraglutide (from Novo Nordisk) and exenatide work by mimicking incretins--gut hormones produced after a meal that increase insulin production. Liraglutide was reviewed by an FDA advisory panel on April 2, which expressed concerns that the drug causes thyroid tumors.
In the randomized trial, John Buse, MD, PhD, from University of North Carolina School of Medicine in Chapel Hill, N.C., and colleagues studied 464 patients--all adults with inadequately controlled type 2 diabetes on maximally tolerated doses of the diabetes drugs metformin, sulphonylurea or both. Of these, 233 received liraglutide 1.8 mg once daily, while 231 received exenatide 10 µg twice-daily. The primary outcome was the change in glycosylated hemoglobin (HbA1c).
The mean baseline HbA1c for the study population was 8.2 percent. The researchers reported that liraglutide reduced mean HbA1c by 1.12 percent, compared with a 0.79 percent reduction for patients on exenatide. More patients achieved an HbA1c level of less than 7 percent in the liraglutide group (54 percent) than in the exenatide group (43 percent).
Liraglutide also reduced mean fasting blood glucose levels by around two-and-a-half times more than did exenatide, according to the investigators. However, exenatide reduced blood glucose more than did liraglutide after breakfast and dinner meals, suggesting that liraglutide exerts more of its effects in the pre-meal or fasting period. Both drugs promoted similar weight loss (liraglutide --3.2 kg vs. exenatide -- 2.9 kg). Both drugs were well tolerated, but nausea was less persistent and low blood sugar less common with liraglutide than with exenatide.
"Liraglutide once-daily provided significantly greater improvements in glycemic control than did exenatide twice a day, and was generally better tolerated," the authors concluded. "The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycemia are major considerations."
In an accompanying commentary, Christophe De Block, MD, PhD, and Luc Van Gaal, MD, from the Antwerp University Hospital and University of Antwerp in Belgium, wrote that the LEAD-6 trial shows that "liraglutide provides greater improvements in glycemic control and is better tolerated than exenatide; therefore, this [treatment] might be a good option for the treatment of type 2 diabetes."