June 9, 2009 (New Orleans, Louisiana) — A head-to-head comparison of the investigational agent liraglutide (Novo Nordisk) and exenatide (Byetta, Amylin Pharmaceuticals) shows that the former resulted in a statistically significantly greater decrease in hemoglobin A1c (1.12% vs 0.79%, respectively).
Results of the Liraglutide Once Daily Compared With Exenatide Twice Daily (LEAD 6) study were presented here yesterday at the American Diabetes Association 69th Scientific Sessions and released simultaneously online in The Lancet.
LEAD 6 involved 464 patients with poorly controlled type 2 diabetes on maximally tolerated doses of metformin, sulfonylurea, or both. They were randomly assigned to liraglutide 1.8 mg once a day or exenatide 10 μg twice a day for 26 weeks. Mean baseline hemoglobin A1c was 8.2%.
By the end of the 26-week study period, liraglutide lowered fasting plasma glucose levels by 1.61 mol/L, compared with a decrease of 0.60 mol/L with exenatide, principal investigator John Buse, MD, chief of endocrinology and director of the Diabetes Care Center at the University of North Carolina School of Medicine in Chapel Hill, told meeting attendees during the special ADA/Lancet symposium.
An average weight reduction of 3 kg occurred in both groups.
Nausea was the most commonly reported adverse event with both agents, with slightly less persistent nausea in the liraglutide group than in the exenatide group.
Hypoglycemia was mild to moderate in both groups, with somewhat fewer episodes with liraglutide than exenatide.
Coinvestigator Lawrence Blonde, MD, director of the Diabetes Clinical Research Unit at the Ochsner Clinic here in New Orleans, told Medscape Diabetes & Endocrinology in an interview just prior to the release of the LEAD 6 findings that "54% of patients on liraglutide achieved target levels of A1c below 7%, compared with 43% on exenatide."
"There was a 0.3 percentage point greater reduction in A1C with liraglutide," Dr. Blonde said.
Effective But Expensive
"These drugs are very good, but expensive," Joel J. Zonszein, MD, an endocrinologist and professor of medicine and director of the Clinical Diabetes Center at the University Hospital of the Albert Einstein College of Medicine, a division of Montefiore Medical Center in the Bronx, New York, commented in an interview prior to the symposium.
"Liraglutide minimally improves A1c and it is better tolerated. Nausea is a problem with both," he noted. "Liraglutide can be given once a day instead of twice, so that's another advantage. But overall, there is no a big difference between the 2."
"Both drugs have been associated with hyperplasia and thyroid cancer in mice, but there is no clinical evidence of that," Dr. Zonszein cautioned. "That is something that the FDA [US Food and Drug Administration] is going to be watching very closely."
A new drug application for liraglutide is currently under review by the FDA. "A 'positive indication for approval' has just come from Europe and Japan in the past month," Dr. Blonde announced, "so the company is expecting approval in the [United States] soon."
That approval may not come, however, as swiftly as the company hopes. An FDA advisory panel that met in early April was sharply divided on the safety of liraglutide, voting 6 to 6 (with 1 member abstaining) that the cancer data in animals were sufficient not to recommend approval. In LEAD 6, only 1 neoplasm was seen in the whole trial; it occurred in the liraglutide group.
LEAD 6 was supported by funding from Novo Nordisk. The study authors report receiving support from Abbott Pharmaceuticals, Amylin Pharmaceuticals, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, Novartis, and Novo Nordisk, among other sources. Dr. Zonszein reports receiving support from Merck, Novo Nordisk, Schering Plough, and Takeda, among other sources.
American Diabetes Association (ADA) 69th Scientific Sessions: ADA/Lancet Symposium: LEAD 6 results. Presented June 8, 2009.
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Cite this: ADA 2009: LEAD 6: Greater A1c Drop With Liraglutide Than Exenatide in Type 2 Diabetes - Medscape - Jun 09, 2009.