ADA: Investigational Type 2 Diabetes Drug Lowers Weight and Improves Insulin Function

WASHINGTON, June 13 - Liraglutide, an investigational injectable drug for type 2 diabetes, has produced significant decreases in HbA1c levels, as well as significant and sustained weight loss, according to phase 2 studies.

Patients on the highest dose of liraglutide had a mean reduction in HbA1c of 1.7%, and lost about 3 kg (6.6 pounds) during a 14 week study, reported Tina Vilsboll, M.D., of Gentofte Hospital in Vedbaekm, Denmark, and colleagues, at the American Diabetes Association meeting here.

In addition, the drug appears to significantly increase insulin secretion by beta cells, especially during the first phase insulin response, the investigators reported.

Liraglutide is an analog of glucagons-like peptide-1 (GLP-1), a naturally occurring hormone that is released from the gastrointestinal tract on ingestion of food. But GLP-1 is normally degraded rapidly by the enzyme dipetidyl peptidase-4 (DPP-4).

Liraglutide is an incretin mimetic, a synthetic analog version of GLP-1 with 97% homology for the naturally occurring hormone, but that 3% difference allows the drug to remain in circulation far longer, with a half-life of 12 hours after subcutaneous injection. Because the drug is a peptide, it cannot be delivered in oral form, as it would be broken down in the intestinal tract, said Dr. Vilsboll.

She and colleagues reported earlier at the same meeting results of a double-blind study in which 165 patients with type 2 diabetes were randomly assigned, after a four-week washout phase, to either placebo or liraglutide once daily via subcutaneous injection in doses of 0.65 mg. 1.25 mg, or 1.9 mg.

The primary endpoint was a reduction in HbA1c levels, which were significantly reduced compared with placebo at all three dosage levels. The difference between the highest dose of the drug and placebo was 1.74% (P<0.0001).

Between 43% and 50% of patients who received the GLP-1 analog had an HbA1c of less than 7%, compared with 8% of patients in the placebo group.

The main adverse event was nausea, which was experienced by 10% of patients in the 1.9 mg group. Diarrhea was also reported in the drug group. The adverse events declined over time, and there were no reports of significant hypoglycemia, Dr. Vilsboll said.

In late-breaking findings reported today, endocrinologist Sten Madsbad, M.D., of the Hvidovre Hospital in Copenhagen reported on a subgroup of 39 patients. At baseline and 14 weeks, the patients were tested for first-phase insulin secretion and maximal beta cell insulin secretory capacity.

In all, 28 of the 39 in this subgroup completed the study and were available for follow-up. The investigators reported that 1.25 mg dose or liraglutide increased maximal beta cell insulin secretory capacity by 114% compared with placebo (P<0.05) and the 1.9 mg dose increased it relative to placebo by 97% (P<0.05).

In addition, the 1.25 mg dose increased first-phase insulin secretion by 124%, and the 1.9 mg dose did so by 107% (P for both <0.05).

"We are excited by these results, as they demonstrate that liraglutide monotherapy significantly improves blood glucose control without risk of major or minor hypoglycemia, is well tolerated, lowers body weight, and may help the body's ability to produce insulin.

Phase III trials of the drug are underway.

Dr. Vilsboll said that she has no financial interest in Novo Nordisk, the maker of liraglutide.