Liraglutide Diabetes Drug Works Well in Trial and Expected Approval Early 2009

In a phase 3 trial, usually the last kind done before marketing approval is sought, liraglutide had greater benefits against type 2 diabetes, the kind that generally develops in the adult years, than a now-standard medication, glimepiride, said a report in the Sept. 25 online issue of The Lancet.

Results of this trial and others have been given to the FDA, which will review them and decide whether to approve the drug for use in the United States, said trial leader Dr. Alan Garber, a professor of medicine, biochemistry and cell and molecular biology at Baylor College of Medicine, in Houston. "It should be out sometime in the first half of next year," Garber said.
Like the other GLP-1 versions, liraglutide has all the advantages of the natural molecule, with longer-lasting activity, said Dr. Sten Madsbad, a professor of endocrinology at the University of Copenhagen in Denmark, who wrote an accompanying editorial.

"First it stimulates insulin production," Madsbad said. "Then it also promotes glucagon release from the pancreas. It also changes appetite, and therefore you eat less."

Glucagon is a hormone that helps manages blood levels of sugar.

The trial was sponsored by the pharmaceutical company Novo Nordisk, which hopes to market the drug. If approved, liraglutide would be the second GLP-1 diabetes medicine on the U.S. market. The first is exenatide (Byetta), which was approved by the FDA in 2005. It is taken by injection twice a day, while liraglutide requires only one daily injection.

Exenatide is actually the form of GLP-1 found in the saliva of the gila monster, explained Dr. John Buse, president for medicine and science at the American Diabetes Association and a professor of medicine at the University of North Carolina. A new formulation of exenatide allowing once-a-week injection has successfully been tested, Buse added.

"There has been a lot of enthusiasm about exenatide based on reports of weight loss," Buse said.

In a head-to-head test, liraglutide was more effective in controlling diabetes, Garber said. The newly reported study, he said, "shows that in patients already taking doses of existing oral medications, they did better when they switched to liraglutide."
In the study, 746 patients with early type 2 diabetes received once-daily 1.2 mg or 1.8 mg doses of liraglutide by injection or once daily Amaryl by oral tablet. Patients getting liraglutide received dummy pills; those getting Amaryl received injections of a harmless, inactive placebo.

Weight loss was also seen in the trial, which ran for one year. Participants taking liraglutide lost an average of 4.4 pounds, while those taking glimepiride gained an average of 2.2 pounds.

Before treatment, patients' HbA1c scores -- a measure of long-term blood-sugar control -- ranged from 7% to 11%. After 52 weeks of treatment: HbA1c dropped 1.14% in patients receiving 1.8 mg doses of liraglutide. HbA1c dropped 0.84% in patients receiving 1.2 mg doses of liraglutide. HbA1c dropped 0.51% in patients receiving Amaryl.

51% of patients getting 1.8 mg doses of liraglutide reached the American Diabetes Association target HbA1c level of less than 7.0%. 43% of patients getting 1.2 mg doses of liraglutide reached the ADA target HbA1c level.  28% of patients getting Amaryl reached the ADA target HbA1c level.

"We want more medications that have this type of profile," Garber said. "It is very well-tolerated, has few side effects and can lead to weight loss. Most diabetes medications now produce weight gain, and that is very discouraging to our patients."
One shadow is a possible risk of pancreatitis, a condition which was reported in two people in the liraglutide trial and whose symptoms include nausea, vomiting and belly pain.

But Garber maintained that "there is unlikely to be a major pancreatitis concern, because it is so rare."

A contest may develop between liraglutide and a once-a-week formulation of exenatide, Buse said. The longer-lasting exenatide version is expected to reach the U.S. market in about a year. It requires a standard hypodermic needle for injection, while liraglutide can be given through a small, ultrafine needle.

Several other GLP-1 drugs are in trials now and might be approved before long, Buse said. "It will be a great opportunity for patients to have so many choices," he added.

The Lancet, online Sept. 25, 2008

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