The FDA has not yet approved liraglutide, although the new findings make eventual approval seem likely. Liraglutide requires once-daily injections. Byetta requires two injections a day, although a once-weekly version is in the works.
Liraglutide and Byetta are analogs of a hormone called GLP-1, which stimulates insulin secretion and expands insulin-making beta cells in the pancreas. A related class of diabetes drugs, the DPP-4 inhibitors, blocks an enzyme that degrades GLP-1. DPP-4 inhibitors include Januvia, approved in the U.S. and Europe, and Galvus, approved in Europe but not in the U.S.
It's not clear whether liraglutide will have the same rare-but-dangerous side effect of pancreatitis seen with Byetta -- although two such cases have been reported in patients receiving liraglutide. Both drugs can cause nausea, vomiting, and diarrhea, although these side effects tend to go away after the first month of treatment.
A downside to the DPP-4 inhibitors is that because DPP-4 plays a role in immunity, patients taking these drugs appear to have an increased risk of infections.
The new study, by Baylor College of Medicine researcher Alan Garber, MD, PhD, and colleagues, did not compare liraglutide directly to Byetta or DPP inhibitors. Instead, the study compared liraglutide to Amaryl, a member of the commonly used class of drugs called sulfonylureas, which stimulate insulin secretion.
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.
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.
Patients treated with liraglutide lost weight, while most of those treated with Amaryl gained weight. Weight loss over the first 16 weeks of the study was maintained at the one-year mark.
Patients who had nausea for more than seven days lost 7.1 pounds on the 1.2 mg dose of liraglutide, 7.5 pounds on the 1.8 mg dose of liraglutide, and 3.15 pounds on Amaryl.
Patients who had no nausea, or nausea for up to seven days, lost 4.1 pounds on the 1.2 mg dose of liraglutide, lost five pounds on the 1.8 mg dose of liraglutide, and gained 2.7 pounds on Amaryl.
Liraglutide also reduced patients' blood pressure more than Amaryl did.
While nausea was a common side effect of liraglutide, only six liraglutide patients dropped out of the study because of vomiting.
"We conclude that liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and has advantages over other drugs used in monotherapy, such as greater reductions in weight, the number of [too-high-blood-sugar] events, and systolic blood pressure," Garber and colleagues conclude.
The findings appear in the Sept. 25 online edition of The Lancet. The study was funded by liraglutide maker Novo Nordisk. Garber has received research grants from the company (as have several other study authors) and serves as an advisory board member. Two of the study authors are Novo Nordisk employees. The researchers had full access to the study data and claim final responsibility for the decision to submit the findings for publication.