LEAD-6: Liraglutide superior to exenatide in improving glycemic control

American Diabetes Association's 69th Scientific Sessions

Liraglutide was associated with greater reductions in HbA1c levels and less persistent nausea than exenatide in patients with type 2 diabetes at 26 weeks, according to the results of the Liraglutide Effect and Action in Diabetes (LEAD) 6 trial.

“The whole class of glucagon-like peptide 1 receptor agonists is very promising,” Lawrence Blonde, MD, director of the Ochsner Diabetes Clinical Research Unit in New Orleans, told Endocrine Today. “This is the first head-to-head study that compared two GLP-1 drugs.”

Liraglutide (Victoza, Novo Nordisk) is currently under investigation as a treatment for type 2 diabetes; exenatide is already on the market (Byetta, Amylin). The study was funded by Novo Nordisk.

The LEAD-6 trial researchers enrolled 464 patients with uncontrolled type 2 diabetes and randomly assigned them to once-daily liraglutide 1.8 mg (n=233) or twice-daily exenatide 10 mcg (n=231). In addition to the GLP-1 drugs, patients continued taking maximally tolerated doses of metformin and/or sulfonylurea.

“Compared with exenatide 10 mcg twice daily, liraglutide 1.8 mg once daily was associated with greater reductions in HbA1c and fasting plasma glucose, greater improvements in beta cell function, no major hypoglycemia and less persistent nausea,” John Buse, MD, professor and chief of endocrinology at the University of North Carolina, Chapel Hill, said.

Buse presented the LEAD-6 data at the American Diabetes Association’s 69th Scientific Sessions on Monday. The data were also published simultaneously in The Lancet.

At 26 weeks, patients assigned to liraglutide experienced a significant 1.12% reduction in HbA1c compared with 0.79% with exenatide. The investigational drug was also associated with a significant reduction in fasting plasma glucose (–1.61 mmol/L vs. –0.60 mmol/L). However, postprandial glucose control was less effective after meals.

More than half (54%) of patients assigned to liraglutide achieved a target HbA1c of <7% compared with 42% of those assigned exenatide.

Weight loss was similar with both treatment regimens — about 3 kg. Nausea, a commonly reported adverse event with GLP-1 receptor agonists, occurred in both treatment groups; however, patients assigned to liraglutide experienced less persistent nausea than those assigned to exenatide.

“By week six, the proportion of patients having nausea in the liraglutide group had fallen to below 10%, whereas in the exenatide group it did not get to below 10% until about 22 weeks,” Blonde said.

Liraglutide-treated patients also experienced fewer minor hypoglycemia events (1.93 per patient-year) than exenatide-treated patients (2.60 per patient-year). Other commonly reported adverse events reported in both groups included diarrhea, indigestion and headache.

Similar to the two-year results of the LEAD-3 trial reported on Sunday at the ADA meeting, the researchers reported no change in calcitonin levels.

An extension trial will involve switching patients on exenatide to liraglutide, Buse said. – by Katie Kalvaitis

For more information:

Buse JBB. ADA/Lancet symposium. Presented at: American Diabetes Association’s 69th Scientific Sessions; June 5-9, 2009; New Orleans.

Buse JBB. Lancet. 2009;doi:10.1016/S0140-6736(09)60659-0.

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