LEAD-3: Two-year data reveal sustained glycemic improvements with liraglutide

American Diabetes Association's 69th Scientific Sessions

Liraglutide monotherapy for two years was associated with significant, sustained improvements in glycemic control and body weight compared with glimepiride monotherapy, according to new results of the LEAD-3 trial.

At two years, patients assigned to once-daily liraglutide 1.8 mg (Victoza, Novo Nordisk) experienced a 1.1% decrease in HbA1c levels from baseline compared with 0.9% with the 1.2-mg dose and 0.6% with glimepiride. Additionally, more patients assigned to the human glucagon-like peptide 1 analog achieved a target HbA1c <7% (1.8 mg, 58%; 1.2 mg, 44%) at two years compared with glimepiride (37%).

The data are similar to the one-year data published in The Lancet in February, which concluded that liraglutide 1.8 mg reduced HbA1c by 1.14% and the majority of patients achieved a target HbA1c of <7%.

LEAD-3 compared the safety and efficacy of once-daily liraglutide at two doses – 1.8 mg and 1.2 mg – and glimepiride 8 mg. The trial had a one-year randomized, double-blind period followed by an open-label extension. About 90% of one-year completers entered the extension and 73% completed two years of treatment.

Liraglutide was associated with sustained weight loss; glimepiride was associated with sustained weight gain. After two years of treatment, mean body weight decreased significantly (-2.7 kg) among patients assigned to liraglutide 1.8 mg compared with an increase of 1.1 kg with glimepiride.

Hypoglycemia (<56 mg/dL) was more than six times less frequent among patients assigned to liraglutide at either dose compared with glimepiride.

In addition, intention-to-treat and two-year completer analyses revealed comparable between-group HbA1c differences. The researchers reported significant reductions in HbA1c, fasting plasma glucose and hypoglycemia with liraglutide vs. glimepiride in an intention-to-treat analysis.

The researchers reported a new finding that calcitonin levels remained stable and did not increase during the two-year period in a subset of 146 randomized patients. Further, there was no differentiation in calcitonin level by treatment.

“There does not seem to be any cause for concern with regard to calcitonin as a marker of excess c-cell stimulation. While there may be some issue with regard to GLP-1 stimulation of c-cells in rodents it does not appear in humans,” Alan J. Garber, MD, Endocrine Today Chief Medical Editor and professor of medicine at Baylor College of Medicine in Houston, said in an interview. – by Katie Kalvaitis

For more information:

Garber AJ. #162-OR. Presented at: American Diabetes Association’s 69th Scientific Sessions; June 5-9, 2009; New Orleans.