Obese adults may shed more weight with the diabetes drug liraglutide than with the weight-loss drug orlistat (Xenical, Alli), suggests a study in The Lancet this week.

The finding that liraglutide was superior to orlistat was unexpected, Dr. Arne Astrup, from the University of Copenhagen, Denmark, told Reuters Health.

Until now, liraglutide has only been tested for its blood sugar-lowering abilities in people with type 2 diabetes. This is the first state of the art trial to test its weight loss properties in obese adults without diabetes, Astrup said.

The biggest findings with liraglutide, Astrup said, were the clear-cut dose-response relationship with weight loss (the higher the dose, the greater the weight loss), the nice reduction in blood pressure, and the cure of patients with pre-diabetes - that is, poor blood sugar control not yet bad enough to qualify as diabetes.

In the study, 564 obese adults without diabetes were randomly assigned to receive liraglutide at one of four doses (1.2, 1.8, 2.4, or 3.0 milligrams), placebo, or orlistat (120 milligrams). Liraglutide and placebo were given once daily as an injection, while orlistat was given three times a day in pill form.

All participants in the study increased their physical activity throughout the trial and followed a calorie-restricted diet, which contained approximately 500 calories less than they needed each day.

People who took liraglutide lost significantly more weight than people who took placebo or orlistat, Astrup and colleagues found. Liraglutide contains a satiety hormone that helps curb appetite.

Average weight loss with the lowest liraglutide dose (1.2 mg) was 4.8 kilograms (10.6 pounds); with 1.8 mg liraglutide, subjects lost an average of 5.5 kg (12.1 pounds); with 2.4 and 3.0 mg liraglutide, subjects lost an average of 6.3 kg (13.9 pounds) and 7.2 kg (15.8 pounds), respectively.

This compares with an average weight loss of only 2.8 kg (6.2 pounds) with placebo and 4.1 kg (9 pounds) with orlistat.

Moreover, 76 percent of subjects taking the highest dose of liraglutide lost more than 5 percent of their body weight compared with only 30 percent on placebo and 44 percent on orlistat.

Liraglutide also lowered blood pressure at all doses.

At the start of the study, about a third of subjects in each group were considered pre-diabetic. At the higher doses, liraglutide cut the number of pre-diabetics significantly -- by 84 to 96 percent.

Nausea and vomiting were reported more often with liraglutide than with placebo, but side effects were usually transient and seldom led to discontinuation of treatment.

Astrup, who is a member of the Liraglutide Obesity Advisory Board of Novo Nordisk, the company developing the drug, noted that liraglutide has to pass phase III trials before it can reach the market in the coming years. However, the drug is available for the treatment of type 2 diabetes in Europe.

Dr. George A. Bray, from Louisiana State University, Baton Rouge, comments in a related editorial: Whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established.

SOURCE: Lancet, online October 23, 2009.

Medicine Glaxosmithkline