Once-daily liraglutide lowers Hb[A.sub.1c] by 1.7% in early trial.

WASHINGTON -- A new glucagonlike peptide-1 agonist known as liraglutide significantly reduced Hb[A.sub.1c] when used as monotherapy in a phase II trial that was presented at the annual scientific sessions of the American Diabetes Association.

Liraglutide, an incretin mimetic developed by Novo Nordisk A/S for once-daily injection, entered phase III testing in February.

The GLP-1 agonist exenatide (Byetta, Amylin Pharmaceuticals Inc. and Eli Lilly and Co.), approved last year by the Food and Drug Administration for use in type 2 diabetes, is administered via twice-daily injection.

Dr. Tina Vilsboll of Gentofte University Hospital in Copenhagen and her associates evaluated liraglutide in a 14-week randomized controlled trial involving 165 patients.

Liraglutide is 97% homologous to native GLP-1 but has two important alterations, she noted. These differences give the analogue a half-life of 12 hours, which makes once-daily dosing possible.

The 1-minute half-life of native GLP-1 means that, for diabetic patients, it would need to be administered via an impractical continuous pump infusion, she noted.

At the highest dose (1.9 mg), there was a mean drop in Hb[A.sub.1c] of 1.7 percentage points, compared with placebo.

Dr. Vilsboll called the absence of hypoglycemia especially noteworthy. Nausea--experienced by 10% of patients--and diarrhea were the most common side effects.

Also notable was a linear reduction in body weight, with no plateau, Continued therapy would likely show even greater weight loss, she speculated.

At a press briefing, ADA vice president Dr. John B. Buse of the University of North Carolina at Chapel Hill commented that the weight loss seen with liraglutide was as high as 20-30 kg (44-66 pounds) in some patients, although others had no weight loss.

Dr. Vilsboll observed that diabetes causes beta cells to deteriorate by 4% every year. Her group conducted a subanalysis of beta-cell function, which showed increased function of these cells in type 2 diabetics; the improvements were most significant with the two highest doses of liraglutide. "This is not just a coincidence, because by now a lot of studies with native GLP-1 have shown that this drug does have a beneficial effect in the beta cells," she said.

BY JOHN R. BELL

Associate Editor