LEAD-6 Study Shows Better Results With Liraglutide Than Exenatide In Controlling Blood Glucose In Type 2 Diabetes

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Main Category: Diabetes
Article Date: 08 Jun 2009 - 15:00 PDT

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The results of the LEAD-6 study are published in an article Online First and in a future edition of The Lancet. The findings are presented at the same time at the American Diabetes Association meeting in New Orleans, USA. They indicate that taking liraglutide once a day is more efficient in controlling blood glucose in type 2 diabetes than the presently marketed treatment - two doses a day of exenatide.

The way those two drugs (liraglutide and exenatide) function is by imitating the gut hormones (incretins) that are produced after eating food and that increase insulin production. Professor John Buse, of the University of North Carolina School of Medicine, Chapel Hill, NC, USA and collaborators studied 464 patients in a randomised trial. All of them were adults with uncontrolled type 2 diabetes receiving maximum tolerated doses of the diabetes drugs metformin, sulphonylurea, or both. The first group of 233 patients received liraglutide 1.8 mg once daily. The second group of 231 patients received exenatide 10 µg twice-daily. The principal result was the change in glycosylated haemoglobin (HbA1c). HbA1c is used to indicate the average plasma glucose concentration of the preceding two to three months. In general, the reference range that is found in healthy persons who do not have diabetes is about 4 to 5.9 percent. Patients with diabetes usually have HbA1c levels above 6.5 percent.

The average baseline HbA1c for the study population was 8.2 percent. With liraglutide the mean HbA1c was reduced by 1.12 percent. For patients on exenatide, the reduction was of 0.79 percent. The number of patients reaching an HbA1c level of less than 7.0 percent was higher in the liraglutide group (54 percent) than in the exenatide group (43 percent). In the liraglutide group, the mean fasting blood glucose levels were reduced by about two-and-a-half times more than in the exenatide group. On the other hand, exenatide was more effective in reducing blood glucose after breakfast and dinner meals, than liraglutide. These findings suggest that liraglutide makes greater use of its effects in the pre-meal or fasting phase. The use of each drug resulted in comparable weight loss, with 3.2kg with liraglutide and 2.9kg with exenatide. In general, both drugs were well accepted. But, with liraglutide there was less nausea and hypoglycaemia caused by low blood sugar was less frequent, than with exenatide.

The authors write in conclusion: "Liraglutide once-daily provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations."

In a supplementary note, Dr Christophe De Block and Dr Luc Van Gaal, of the Antwerp University Hospital and the University of Antwerp, Belgium,remark: "The LEAD-6 trial shows that liraglutide provides greater improvements in glycaemic control and is better tolerated than exenatide; therefore, this [treatment] might be a good option for the treatment of type 2 diabetes."

"Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)"
John B Buse, Julio Rosenstock, Giorgio Sesti, Wolfgang E Schmidt, Eduard Montanya, Jason H Brett, Marcin Zychma, Lawrence Blonde, for the LEAD-6 Study Group
DOI:10.1016/S0140-6736(09)60659-0
thelancet

Written by Stephanie Brunner (B.A.)
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