Liraglutide superior to glimepiride in lowering HbA1c levels, weight

Liraglutide, a GLP-1 receptor agonist, reduced HbA1c levels, weight, hypoglycemia and blood pressure to levels lower than achieved with glimepiride, according to data from a recently published phase-3 trial.

Researchers from the Baylor College of Medicine in Houston, the University of California at San Diego School of Medicine and other sites in the United States and Mexico, conducted a double-blind, double-dummy, active-control, parallel-group study to determine the safety and efficacy of liraglutide as initial pharmacological therapy for patients with type 2 diabetes.

“This is the first one-year trial of a GLP-1 agonist, or any incretin-based therapy, that shows relatively good, durable glucose control in contrast to the failing control seen with a sulfonylurea,” Alan Garber, MD, PhD, professor at the Departments of Medicine, Biochemistry and Molecular Biology and Cellular and Molecular Biology at Baylor College of Medicine told Endocrine Today. Garber is also Endocrine Today’s Chief Medical Editor.

The study included 746 patients with early type 2 diabetes aged between 18 and 80 years. Patients were randomly assigned to liraglutide 1.2 mg (n=251) or 1.8 mg (n=247) or glimepiride 8 mg (n=248) once per day for 52 weeks. Doses of each drug were titrated after randomization.

At baseline, mean HbA1c was 8.2%, mean fasting plasma glucose was 9.5 mmol/L, mean weight was 92.6 kg and mean blood pressure was 129/79 mmHg.

In the liraglutide group, HbA1c levels decreased by 0.84% for the patients receiving the 1.2-mg dose and to 1.14% for those receiving the 1.8-mg dose, compared with 0.51% for the glimepiride group. There was a –0.62% difference in the decrease of HbA1c between glimepiride and liraglutide 1.8 mg (P<.0001) and a –0.33% difference between glimepiride and liraglutide 1.2 mg (P=.0014).

Patients assigned to liraglutide who were previously treated with diet and exercise had greater decreases in HbA1c levels than those treated previously with oral antidiabetic drugs.

At the study’s close, 28% of participants assigned to liraglutide 1.2 mg and 38% of those assigned to 1.8 mg reached the International Diabetes Federation/American Association of Clinical Endocrinologists target HbA1c of 6.5%, compared with 16% of participants assigned to glimepiride, according to the researchers.

The researchers reported weight loss in patients assigned to liraglutide and weight gain in those assigned to glimepiride. Reductions in blood pressure and hypoglycemia were more significant in both liraglutide groups than in the glimepiride group, the researchers wrote.

“Liraglutide clearly improves glucose control better than sulfonylureas and promotes weight loss rather than weight gain with very low rates of hypoglycemia,” Garber said. – by Stacey L. Adams

Lancet. 2008;doi:10.1016/S0140-6736(08)61246-5.

The comparison of liraglutide 1.2 mg to 1.8 mg with glimepiride 8 mg daily showed a number of important differences between the agents. Liraglutide was clearly more potent in glucose lowering, caused about half as much hypoglycemia and led to a 2-kg weight loss as opposed to the 1-kg weight gain with glimepiride. These are important considerations suggesting that the agent might be appropriate for initial glycemic treatment of type 2 diabetes.

There were, as expected, more gastrointestinal adverse events with liraglutide. A particular concern, however, is the two cases of pancreatitis occurring in the 500 patients receiving the agent. Given the reports of pancreatitis with exenatide LAR (Byetta, Amylin), this must now be considered a potential adverse effect of the class of GLP-1 receptor agonists, and it is possible that long-acting agents such as liraglutide and exenatide LAR will be associated with higher rates of this complication.

– Zachary T. Bloomgarden, MD

Endocrine Today Editorial Board member