News Article
Liraglutide Plus Metformin and Rosiglitazone Cut HbA1c, Body Weight, and Blood Pressure
ROME (EGMN) - The investigational, once-daily, human glucagon-like peptide-1 analog, liraglutide, produced a 1.5 percentage point drop in hemoglobin A
The findings of this 26-week phase IIIA randomized, placebo-controlled trial of 533 patients were reported by Dr. Bernard Zinman at a press briefing held during the annual meeting of the European Association for the Study of Diabetes.
The LEAD (Liraglutide Efficacy and Action in Diabetes) 4 trial, sponsored by Novo-Nordisk, comprised 533 subjects with a mean age of 55 years, mean body mass index of 33.5 kg/m², and mean HbA
At 26 weeks, HbA
The proportions who achieved an HbA
More than a third of both groups (36% of those on the 1.2-mg dose and 37% of those on the 1.8-mg dose) achieved HbA
Fasting plasma glucose (FPG) levels also dropped significantly with both liraglutide doses (by 2.2 mmol/L with 1.2 mg and by 2.4 mmol/L with 1.8 mg) to final FPG levels of 7.7 mmol/L and 7.6 mmol/L, respectively. The FPG drop in the placebo subjects was just 0.4 mmol/L (to 9.5 mmol/L).
Body weight dropped by 1.02 kg with the 1.2-mg dose and by 2.02 kg with the 1.8-mg dose, both statistically significant changes; placebo subjects gained an insignificant 0.60 kg.
Mean systolic blood pressure levels were reduced by 6.7 mm Hg with the 1.2-mg dose and by 5.6 mm Hg with the 1.8-mg dose, compared with just 1.1 mm Hg with placebo, which were also statistically significant differences.
No major hypoglycemic episodes were reported during the study. Minor hypoglycemia (defined as less than 3.1 mmol/L), occurred in 9% of the 1.2-mg group, 8% of the 1.8-mg group, and 5% of the placebo group. The rate of 0.64 events per subject per year that was seen in the 1.8-mg group was statistically significant, compared with the 0.17 rate seen in the placebo group.
Nausea was the most common adverse event reported, occurring in 29% of the 1.2-mg group and 40% of the 1.8-mg group, compared with just 9% with placebo. Nausea occurred early in the treatment regimen and returned to placebo levels after the first 16 weeks of the study, Dr. Zinman noted.
On May 23, 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the United States, as well as a marketing authorization application to the European Medicines Agency for the approval of liraglutide for the treatment of type 2 diabetes. A New Drug Application was also submitted for approval in Japan on July 15, 2008. If approved, liraglutide would be the first human-derived GLP-1 analog.
Exenatide (Byetta), the GLP-1 mimetic currently on the market, is derived from the salivary gland of a lizard.
Novo-Nordisk has completed a head-to-head comparison study that compares liraglutide with exenatide, both combined with metformin and sulfonylurea. Those results will be presented in October at the Canadian Diabetes Association annual meeting in Quebec.
Dr. Zinman is a consultant for Novo Nordisk Inc.
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