LISBON – Obese individuals who have already managed to lose weight via diet and exercise can keep the pounds off by taking the antidiabetic drug liraglutide, even it they do not have diabetes, data from a yearlong study suggest.
Data from the 56-week, phase III SCALE (Satiety and Clinical Adiposity Liraglutide Evidence in Nondiabetic and Diabetic Subjects) study showed that body weight was decreased by 6.11% in the 212 liraglutide-treated patients but by just 0.05% in the 210 who were given placebo in association with a low-calorie diet, a highly significant difference.
Dr. Vincent Woo
Novo Nordisk’s liraglutide (Victoza) is a long-acting glucagonlike peptide–1 (GLP-1) analogue that has been developed to treat people with type 2 diabetes. As such, it is not licensed for use in obese individuals who do not have diabetes.
However, these new data suggest that it could potentially be used to help nondiabetic people who have lost weight but are having trouble maintaining their reduced weight.
Reporting the findings of the final 12-week "off treatment" follow-up phase at the European Association for the Study of Diabetes annual meeting, Dr. Vincent Woo of the University of Manitoba, Winnipeg, said that the patients who were included in the trial were basically "unsuccessful dieters."
The subjects had to have a body mass index of 30 kg/m2 or greater, or a body mass index greater than 27 with comorbidities, and have already achieved a stable weight loss of 5% or more with a low-calorie (1,200-1,400 kcal/day) diet and exercise plan. A total of 422 individuals (mean age, 46 years) took part in the trial.
The objective was to assess if up to 3 mg/day of liraglutide could help maintain this weight loss, Dr. Woo said, and to see if there was any additional weight loss that could be achieved with the drug, compared with diet and exercise alone.
Three coprimary end points at week 56 were the mean percent change in body weight from randomization; the percentage of individuals who maintained their weight loss after the 4- to 12-week run-in period; and the percentage of individuals who lost an additional 5% or more of their body weight after randomization.
For the drug to be proved better than diet and exercise alone, all three coprimary end points had to be met, and they were.
"If we look at the mean change in weight from randomization to week 56, there was a significant loss of weight in the liraglutide group of 6.1%," compared with minimal changes for the placebo group, Dr. Woo said, adding that the liraglutide group lost a mean 5.7 kg, compared with a slight increase of 0.16 kg in the placebo group.
A significantly higher percentage of the liraglutide group (51% vs. 22% of those on placebo) were able to achieve a 5% additional weight loss at 56 weeks, with 26% and 6.3%, respectively, achieving an additional 10% weight loss.
The majority (81%) of individuals treated with liraglutide were able to maintain their run-in weight loss, compared with about half (46%) of placebo-treated subjects. Only 1.9% of liraglutide – but 18% of placebo-treated individuals – regained 5% body weight during the trial. Both differences were highly significant.
Dr. Woo noted that liraglutide was generally well tolerated with "no major safety issues," compared with placebo. Both groups reported a similar percentage of any adverse events (91.5% vs. 88.8%, respectively). Likewise, there was no difference in the percentage of patients experiencing serious adverse events or withdrawing from the study as a result.
Dr. Woo said that the gastrointestinal adverse effects were to be expected with the GLP-1 agonist. They included nausea (48% vs. 17% in the placebo group), constipation (27% vs. 12%), diarrhea (18% vs. 12%), and vomiting (17% vs. 2%). Only 2.4% of individuals on liraglutide withdrew because of nausea, however, which Dr. Woo said occurred in the first 4-5 weeks and was generally mild in 64% of patients.
Unlike other drugs that have been used to manage obesity, there was no indication that liraglutide increased the risk of psychiatric disorders.
"The obesity indication is always a tough one for regulatory authorities," commented Dr. Michaela Diamant, professor of diabetology and director of the diabetes center at the Free University Medical Center in Amsterdam, in an interview. She chaired the session in which the SCALE findings were reported, but was not involved in the study.
Although liraglutide may become a preferred agent for an obese, diabetic patient and for those in whom an additional weight maintenance benefit would add to improved glycemic control, its use in someone who is simply obese is likely to be more controversial, especially because the drug must be administered via a daily subcutaneous injection.