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Liraglutide Controls Glucose, Promotes Weight Loss in Type 2 Diabetes

Jan 28, 2009

Liraglutide appears to control glucose levels as well as does glimepiride when given with metformin, with the added benefit of weight loss, a new phase III trial has concluded.

Patients taking any of the three liraglutide doses tested lost weight in a dose-dependent manner (2-3 kg), while those taking glimiperide gained a mean of 1 kg by the end of the 26-week trial, Dr. Michael Nauck and his colleagues reported.

Patients taking liraglutide also experienced significant decreases of 2-3 mm Hg in systolic blood pressure, compared with those taking glimepiride, for unknown reasons, the authors noted. “On the basis of the systolic blood pressure and weight profiles over time, the reduction in blood pressure may not be fully explained by the reduction in body weight,” wrote Dr. Nauck of the Diabeteszentrum, Bad Lauterberg, Germany, and his coinvestigators.

Liraglutide is a human analog of glucagonlike peptide-1 (GLP-1). It stimulates glucose-dependent insulin secretion, decreases glucagon secretion, slows gastric motility and emptying, and reduces appetite, the investigators said.

The Liraglutide Effect and Action in Diabetes-2 (LEAD) study enrolled 1,091 adults with type 2 diabetes who were taking metformin; patients also had to have a body mass index of at least 40 kg/m2. They were randomized to one of three daily liraglutide doses (0.6, 1.2, or 1.8 mg subcutaneously) with metformin, to 4 mg/day glimepiride with metformin, or to metformin monotherapy with a liraglutide placebo. The 2-week titration period was followed by a 24-week maintenance phase.

At the end of the study, the mean hemoglobin A1c (HbA1c) level reductions in the 1.2- and 1.8-mg liraglutide groups equaled those seen in the glimepiride group (1%). The percentages of patients taking either active drug who reached the HbA1c goal set by the American Diabetes Association or the goal set by the American Association of Clinical Endocrinologists were similar. Fasting plasma glucose levels decreased similarly in both active groups (1-1.7 mmol/L for liraglutide vs. 1.3 mmol/L for glimepiride).

However, patients taking liraglutide lost weight, while those taking glimepiride and those in the placebo (metformin-only) group gained weight. Weight loss was dose dependent for liraglutide; the mean loss for those taking 1.2 mg/day was 2 kg, while those taking 1.8 mg/day lost a mean of 3 kg. Patients taking glimepiride gained a mean of 1 kg and patients taking only metformin gained a mean of 1.5 kg.

Although nausea and vomiting were the most commonly reported adverse effects (occurring in 35%-44% of the liraglutide groups and 17% of the glimepiride and placebo groups), the authors said those symptoms didn’t cause the weight loss. “The great majority of subjects either did not report nausea or reported nausea for 7 days or less.”

Patients taking the 1.2- and 1.8-mg doses of liraglutide also experienced a significant reduction in systolic blood pressure (2-3 mm Hg), while those taking glimepiride experienced a slight increase of 0.4 mm Hg. There were no changes in diastolic pressure.

Diabetes Care, Jan.2008;32:84-90.