Switching from exenatide to investigational GLP-1 analog improves glycemic control with low risk of hypoglycemia

June 8, 2009

Switching from twice-daily exenatide to the investigational once-daily liraglutide improves glycemic control in patients with type 2 diabetes on a background of metformin and/or a sulfonylurea.

Switching from twice-daily exenatide to the investigational once-dailyliraglutide improves glycemic control in patients with type 2 diabetes on abackground of metformin and/or a sulfonylurea, reports John Buse, MD, PhD, professorand chief of endocrinology at the University of North Carolina, Chapel Hill(pictured left).

Liraglutide is a human glucagon-like peptide (GLP)-1 analog under review by theFood and Drug Administration.

"Exenatide is an animal protein that is 53% identical to human GLP-1, whereasliraglutide is about 95% identical. Exenatide is not degraded by dipeptidylpeptidase (DPP)-IV and is cleared renally. Liraglutide is metabolized; it’s notreally cleared renally. The half-life of liraglutide is longer," says Dr. Buse incontrasting the two agents.

"With regard to glycemia, it seems that liraglutide lowers A1c a bitmore, lowers fasting glucose a lot more, lowers postprandial glucose a little bitless, seems to have a modestly better effect on blood pressure and lipids, and ismodestly better tolerated with regard to nausea and mild hypoglycemia.”

Liraglutide was compared with exenatide in a 26-week randomized trial known asLEAD-6 (Liraglutide Effect and Action in Diabetes 6), which demonstrated liraglutideto be superior to exenatide in improving glycosylated hemoglobin A1c(HbA1c) levels and beta cell function in patients with type 2 diabetes onbackground therapy of metformin and/or a sulfonylurea.

The data presented by Dr. Buse were a 14-week extension of LEAD-6, in which the186 patients initially randomized to exenatide 10 µg twice daily were switched toliraglutide 1.8 mg once daily. Two hundred others who were initially assigned toliraglutide as part of the double-blind portion of the study continued on thedrug.

Among those who switched, mean HbA1c levels decreased by 0.3%(p<0.0001). Following the switch, treatment HbA1c levels weresimilar to those in the patients who continued on liraglutide.

During the extension phase, the proportion of patients who achieved anHbA1c level less than 7.0% increased from 43% to 57% among the patientswho switched from exenatide to liraglutide and from 54% to 61% among those whoremained on liraglutide.

Fasting plasma glucose was lowered an additional 16.2 mg/dL (p<0.0001)after switching from exenatide to liraglutide.

A significant decrease in body weight was observed during the extension phaseamong patients who switched from exenatide to liraglutide (–0.9 kg;p<0.0001) and among those who continued on liraglutide (–0.4 kg;p<0.01).

There were also significant improvements in beta cell function(p≤0.01) and systolic blood pressure (p<0.0001) in the thosewho switched.

The rate of minor hypoglycemia dropped from 2.6 events per patient per year to1.3 events per patient per year after the switch.