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Diabetes 'Zindex' Composite Favors Liraglutide


 

Major Finding: A significantly greater proportion of patients on 1.8 mg/day of liraglutide (39%) achieved an HbA1c level below 7% with no weight gain and no confirmed hypoglycemia by the end of the 26- to 52-week studies, compared with those on twice-daily injections of the GLP-1 agonist exenatide (24%) or patients treated with glargine (15%), a sulfonylurea (8%), placebo (8%), or a thiazolidinedione (6%).

Data Source: A secondary analysis that combined data from the more than 3,900 patients in the LEAD studies to compare the effectiveness of various therapies.

Disclosures: Dr. Buse has been a consultant for, or received research support from, Novo Nordisk Inc. (which markets liraglutide), and Amylin Pharmaceuticals Inc. and Eli Lilly & Co. (which together are marketing the long-acting version of Amylin's exenatide). He has held stock in Insulet Corp., which makes an insulin pump.

SAN FRANCISCO — The once-daily drug liraglutide may work better than other diabetes medications to help patients reach a combination of goals, a secondary analysis of data from pivotal liraglutide studies suggests.

The Food and Drug Administration approved the use of liraglutide (Victoza) in January for adults with type 2 diabetes who fail first-line drug therapy, based on data from the pivotal Liraglutide Effect and Action in Diabetes (LEAD) studies. Liraglutide is an injectable human glucagonlike peptide–1 (GLP-1) analogue.

The LEAD trials were “truly heroic” in their number, breadth, and head-to-head comparisons between existing diabetes medications, and in most of those trials liraglutide was found to be more effective at lowering hemoglobin A1c levels, Dr. John B. Buse said at a meeting sponsored by the American Diabetes Association.

Dr. Buse reported on an analysis that combined data from the more than 3,900 patients in the LEAD studies to compare the effectiveness of various therapies at achieving a composite end point known among diabetologists as a “Zindex.” (The idea was first proposed by Dr. Bernard Zinman, who is professor of medicine at the University of Toronto.)

The analysis assessed the proportion of patients achieving the Zindex of an HbA1c level below 7% with no weight gain and no confirmed hypoglycemia (minor or severe) by the end of the 26- to 52-week studies.

A significantly greater proportion of patients on 1.8 mg/day of liraglutide achieved this Zindex (39%), compared with those on twice-daily injections of the GLP-1 agonist exenatide (24%) or patients treated with glargine (15%), a sulfonylurea (8%), placebo (8%), or a thiazolidinedione (6%).

“An A1c less than 7% without weight gain or hypoglycemia is something that's of substantial interest to patients and clinicians,” said Dr. Buse, chief of endocrinology and director of the diabetes care center at the University of North Carolina at Chapel Hill.

A second analysis compared the data with a second Zindex that combines three goals identified as standards of care by the American Diabetes Association in 2008: an HbA1c less than 7%, no weight gain, and a systolic blood pressure less than 130 mm Hg. The GLP-1 therapies in general have modest effects on blood pressure and lipids, with potentially greater changes in blood pressure on long-acting GLP-1 agonists, Dr. Buse noted.

Again, a significantly greater proportion of patients on 1.8 mg/day of liraglutide (25%) achieved the second Zindex, compared with patients on exenatide (14%), a sulfonylurea (7%), glargine or placebo (5% each), or a thiazolidinedione (3%).

“This is of considerable interest, particularly in our pay-for-performance kind of world,” he said.

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