Liraglutide was safe, effective for treatment of type 2 diabetes

HbA1c values decreased 0.84% in the 1.2-mg liraglutide group, 1.14% in the 1.8-mg liraglutide group compared with 0.51% in the glimepiride group.

As initial pharmacotherapy for type 2 diabetes, liraglutide was safe and effective and led to greater decreases in weight, blood pressure and hypoglycemic events.

In a 52-week, phase-3 study, researchers randomly assigned patients with early type 2 diabetes to once-daily 1.2-mg liraglutide (n=251), 1.8-mg liraglutide (n=247) or 8-mg glimepiride (n=248). Patients were aged 18 to 80 years. In the drug naive population, liraglutide 1.8 mg reduced HbA1c by 1.6% and the majority of patients achieved the American Diabetes Association's recommended HbA1c goals of <7%.

Liraglutide monotherapy was therapeutically superior to a widely used sulfonylurea as first-line therapy for patients with type 2 diabetes, according to Alan J. Garber, MD, PhD, professor in the department of medicine, division of diabetes, endocrinology and metabolism at Baylor College of Medicine in Houston. He is also the chief medical editor of Endocrine Today.

“There were striking collateral benefits with liraglutide as compared with glimepiride [Amaryl, Sanofi-Aventis],” he told Endocrine Today. “Also, liraglutide can be taken at a time of day convenient to the patient and without regard to meals, so it poses no undue burden upon patient adherence.”

Improvements shown

There was a 0.84% reduction in HbA1c values for the 1.2-mg liraglutide group and a 1.14% reduction for the 1.8-mg liraglutide group. In the glimepiride group, there was a 0.51% reduction, according to Garber and colleagues.

The difference in reduction of HbA1c was –0.62% between glimepiride and the 1.8-mg liraglutide group (95% CI, –0.83 to –0.42). The difference between glimepiride and the 1.2-mg liraglutide group was –0.33% (95% CI, –0.53 to –0.13). The reduction with the larger dose of liraglutide was greater than the lesser dose (–0.29%; 95% CI, –0.50 to –0.09).

Reductions in HbA1c were greater in patients previously treated with diet and exercise than patients previously treated with oral antidiabetic monotherapy. In the 1.8-mg liraglutide group, 38% (P<.0001) of patients reached the International Diabetes Federation/American Association of Clinical Endocrinologists HbA1c target of ≤6.5%; 28% of patients in the 1.2-mg liraglutide group (P=.0025) and 16% of patients in the glimepiride group reached the target.

Fasting plasma glucose concentrations were 8.65 mmol/L in the 1.2-mg liraglutide group and 8.25 mmol/L in the 1.8-mg liraglutide group vs. the glimepiride group (9.27 mmol/L), according to the study. Patients who reached the ADA target (5.0 mmol/L-7.2 mmol/L) included 37.6% of the lesser-dose liraglutide group, 41.4% of the greater-dose liraglutide group and 22.2% of the glimepiride group (P<.0001).

In the glimepiride group, a 0.85% increase in insulin resistance (P=.0249) was observed compared with decreases in both the 1.2-mg liraglutide group (0.65%; P=.0249) and the 1.8-mg liraglutide group (1.35%; P=.0011).

Weight loss was observed in both liraglutide groups and weight gain was observed in the glimepiride group. There was a decrease of 0.7 mm Hg in systolic BP for the glimepiride group vs. the 1.2-mg liraglutide group (2.1 mm Hg) and the 1.8-mg liraglutide group (3.6 mm Hg).

There were no major hypoglycemic events, however, minor events occurred in 8% of the 1.8-mg liraglutide group, 12% of the 1.2-mg liraglutide group and 24% of the glimepiride group. A larger proportion of patients experienced nausea in the liraglutide groups (1.2 mg=27.5%; 1.8 mg=29.3%) vs. the glimepiride group (8.5%; P<.0001).

“The 1.8-mg dose of liraglutide showed highly durable and nearly constant glucose control during the entire one-year duration of the randomized, prospective trial, in contrast to the lack of durable control noted with glimepiride,” said Garber.

“This observation suggests a fundamental benefit with regard to beta cell function with liraglutide but not with a sulfonylurea. As type 2 diabetes is a progressive disorder of beta cell deterioration, agents that reduce or eliminate such deterioration may be highly preferred over those that have no beta cell benefit,” he said. – by Christen Haigh

Lancet. 2009;373:473-481.

Increasing the number of available therapies for type 2 diabetes is beneficial for patients. In this active-comparator trial, the researchers reported that liraglutide, either 1.2 mg or 1.8 mg daily, improved glycemic control better than glimepiride 8 mg daily as monotherapy. The results are limited by high dropout rates, and it is important to note that most patients did not reach glycemic control targets. Nevertheless, liraglutide will be a useful agent for some patients.

– Robert D. Blank, MD, PhD

Endocrine Today Editorial Board member