News Article
Study Finds Liraglutide Monotherapy Provides Safe and Effective Glycemic Control
Monotherapy with liraglutide resulted in significantly better glycemic control over 52 weeks, with a low rate of hypoglycemia, than monotherapy with oral glimepiride, a study has found.
The patients on liraglutide in the 52-week study had greater drops in glycosylated hemoglobin (HbA
Liraglutide, which is not yet approved, is an analogue of endogenous human glucagon-like peptide-1 (GLP-1) "which stimulates glucose-dependent insulin secretion, suppresses glucagon secretion, and moderates appetite by delaying gastric emptying and reducing hunger," according to the study's authors. It is injected subcutaneously once a day. Because it has a half-life of 13 hours, it can be used once daily and "restores glucose-dependent insulin secretion after one injection" in patients with type 2 diabetes. The study was published in the Lancet online Sept. 25 (doi:10.1016/S0140-6736(08)61246-5).
"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 hypoglycemic events, and systolic blood pressure," wrote Alan Garber, Ph.D., of Baylor College of Medicine, Houston, and his associates. "The increased insulin secretion with liraglutide, being glucose-dependent, retains more physiological stimulus-secretion coupling between glucose and insulin than does a sulfonylurea that acts by potassium-channel closure, and produces more hypoglycemia than does a GLP-1 agonist."
The 52-week, phase III study, conducted in the United States and Mexico, compared two subcutaneous doses of liraglutide, 1.2 mg per day or 1.8 mg per day, to 8 mg of oral glimepiride per day in 746 patients aged 18-80 years with early type 2 diabetes. The patients had had diabetes for about 5 years, had a mean body mass index of about 33 kg/mg², and a mean HbA
At 52 weeks, the primary outcome, the change in HbA
At 52 weeks, 28% of those on 1.2 mg of liraglutide and 38% of those on 1.8 mg had reached the International Diabetes Federation/American Association of Clinical Endocrinologists target HbA
None of the participants had a major hypoglycemia episode. Minor episodes of hypoglycemia were experienced by 12% of those on 1.2 mg and 8% of those on 1.8 mg of liraglutide, compared with 24% among those on glimepiride, another significant difference.
More patients on liraglutide stopped treatment because of vomiting, however (five patients on the 1.2-mg dose and one on the 1.8-mg dose) but none of the patients on glimepride stopped treatment because of nausea. Almost 30% of those on liraglutide experienced nausea during treatment, vs. 8.5% of those on glimepride, but nausea tended to occur early in treatment and decreased with time.
Vomiting was significantly more common among the patients on liraglutide, compared with those on glimepiride, and diarrhea was also more common. Overall, 2%-4% of the patients on liraglutide stopped treatment because of vomiting, nausea, or diarrhea, compared with none of the patients on glimepiride.
One or more serious adverse events occurred in 8 patients on 1.8 mg liraglutide, 16 patients on 1.2 mg liraglutide, and 13 patients on glimepiride. These included two cases of pancreatitis in patients on liraglutide, who recovered, with one remaining in the study. However, "despite confounding medical factors and the small number of events, a weak association between development of pancreatitis and treatment with liraglutide cannot be excluded," the authors said.
The study was funded by Novo Nordisk, which has submitted a new drug application with the Food and Drug Administration for approval of liraglutide for treating type 2 diabetes. If approved, it would be the first human-derived GLP-1 analogue on the market. Two authors were from Novo Nordisk. Some authors disclosed having attended speakers bureau of, consulting for, receiving research grants from, and/or serving as an advisory board member or consultant for the company.
In an accompanying editorial, Dr. Sten Madsbad, of the department of endocrinology, Hvidovre (Denmark) Hospital and the University of Copenhagen, wrote that while incretin-based therapies "offer new options" in treating people with type 2 diabetes, "their final role in the therapy of type 2 diabetes remains to be clarified, after carefully conducted long-term trials with cardiovascular endpoints and safety data" (doi:10.1016/S0140-6736(08)61247-7).
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