Weight loss greater with higher-dose liraglutide in diabetes

SAN FRANCISCO – A once-daily subcutaneous injection of an experimental 3-mg dose of liraglutide was significantly more effective than the approved 1.8-mg dose or placebo for weight loss in a randomized, double-blind study of 846 overweight or obese adults with diabetes.

All treatment arms also employed caloric reduction and exercise for weight management. After 56 weeks of therapy, body weight decreased by 5.9% in the 3-mg group, 4.6% in the 1.8-mg group, and 2% in patients on placebo. The mean changes in both liraglutide groups were significantly better than on placebo, and the greater loss on 3 mg, compared with 1.8 mg of liraglutide, also was statistically significant, Dr. Melanie Davies and her associates reported at the annual scientific sessions of the American Diabetes Association.

Dr. Melanie Davies

The percentages of patients who lost at least 5% of body weight by 56 weeks were 50% in the 3-mg group, 36% in the 1.8-mg group, and 14% on placebo. Again, liraglutide at either dose was significantly more effective than placebo, and the higher dose of liraglutide worked significantly better than the lower dose, reported Dr. Davies, professor of diabetes medicine at the University of Leicester (England).

The percentages of patients who lost at least 10% of body weight were 23% in the 3-mg group, 14% in the 1.8-mg group, and 4% on placebo. The same statistical trends were seen, with the higher dose being significantly more effective.

Among secondary outcomes in the SCALE-Diabetes trial (Effect of Liraglutide on Body Weight in Overweight or Obese Subjects with Type 2 Diabetes), greater reductions were seen in hemoglobin A_1c levels after 56 weeks on the higher drug dose. HbA_1c levels fell by 1.3% on the 3-mg dose, compared with 1.1% on the 1.8-mg dose or 0.3% on placebo, Dr. Davies said.

The proportions of patients achieving an HbA_1c level of 6.5% or lower were 57% in the 3-mg group, 46% in the 1.8-mg group, and 15% on placebo. The proportions of patients achieving an HbA_1c level below 7% were 69% in the 3-mg group, 67% in the 1.8-mg group, and 27% in the placebo group. Fasting glucose levels decreased by 34 mg/dL in the 3-mg group, 25 mg/dL in the 1.8-mg group, and 2 mg/dL on placebo. In each case, the 3-mg dose was more effective than the lower dose or placebo, except that the likelihood of getting HbA_1c below 7% was not significantly different between the 3-mg and 1.8-mg liraglutide groups.

Systolic blood pressure measurements decreased by a mean of 3.5 mmHg in the 3-mg group, 2.8 mmHg in the 1.8-mg group, and 0.4 mmHg in the placebo group.

Thirty-four percent in the 3-mg group withdrew before the end of the study, as did 22% in the 1.8-mg group and 23% on placebo.

Rates of side effects were not significantly different between the two liraglutide groups, except for gastrointestinal events, Dr. Davies said. Adverse events were seen in 93% on 3 mg liraglutide, 90% on the 1.8-mg dose, and 86% on placebo. Serious adverse events occurred in 9% in either liraglutide group and in 6% on placebo, and side effects led to withdrawal from the study in 9% of either drug group and in 3% on placebo. Severe episodes of adverse events occurred in 12% in the 3-mg group, 14% in the 1.8-mg group, and 10% on placebo. One death in the 1.8-mg group that occurred after the study ended was not considered to be related to treatment, she said.

The most common side effects were nausea (in 33% on 3 mg, 31% on 1.8 mg, and 14% on placebo), diarrhea (26%, 18%, and 13%, respectively), constipation (16%, 10%, and 6%, respectively), and vomiting (16%, 10%, and 6%, respectively). Most of the increase in nausea among those on the drug resolved by 24 weeks.

Hypoglycemia occurred in 44% of the 3-mg group, 40% of the 1.8-mg group, and 28% in the placebo group and was more common in patients on liraglutide and in patients who also were taking sulfonylurea drugs, she said.

A separate SCALE study in 3,731 nondiabetic patients (Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects with Comorbidities) found that the 3-mg dose was more effective for weight loss than placebo in adults without diabetes. Although that study detected rates of pancreatitis and gallbladder disorders that were more than twice as common (though still rare) with liraglutide, compared with placebo, there were no episodes of pancreatitis in the current trial, Dr. Davies said. There was no difference in levels of amylase, which is a marker of pancreatitis, between the two drug arms.