Overweight and obese patients taking liraglutide (Saxenda) lost more weight than those on placebo…
According to a study of 3,731 patients, those on liraglutide lost an average of 8.4±7.3 kg of body weight, and those in the placebo group lost an average of 2.8±6.5 kg (P<0.001). The full results of the study come from a year-long randomized trial — appearing in print more than 2 years after the study was completed and 6 months after the drug was approved for a weight-loss indication. More than 63% of patients on the drug lost at least 5% of their body weight versus 27% of the placebo group, according to the study. Both groups received lifestyle interventions and counseling. In addition, 33.1% of those in the treatment group, compared with 10.6% in the placebo group, lost more than 10% of their body weight (P<0.001). But more patients in the liraglutide group withdrew from the trial early because of adverse events (9.9% versus 3.8%).
“The treatment effect was similar in patients with prediabetes and those without prediabetes and was similar across body mass index categories,” wrote Pi-Sunyer and colleagues. In addition, the researchers found that there was a greater reduction in glycated hemoglobin, fasting glucose, and fasting insulin levels in the liraglutide group than in the placebo group.
Liraglutide is a glucagon-like peptide-1 receptor and is approved as Victoza for treating type 2 diabetes, and has been reformulated as Saxenda for weight loss. The latter version hit the market at a cost of $1,000 a month earlier this year after getting FDA approval last December.
There had been some concern that the adverse gastrointestinal (GI) effects were responsible for the weight loss, but a study from earlier this year by David Lau, MD, PhD — who was also an author of the new study in NEJM and who is at the University of Calgary — found that patients lost weight independent of those effects.
SCALE was conducted from June 2011 to March 2013 at 191 different sites in 27 countries. All of the participants were older than 18 and had a body mass index (BMI) of greater than 30, or 27 if they had dyslipidemia or hypertension. They were assigned to either liraglutide or placebo at a 2:1 ratio, plus diet and exercise interventions and counseling.
Secondary end points of the study included change in body mass index, waist circumference, glycemic control variables, cardiometabolic biomarkers, and health-related quality of life. Most of these also showed greater improvements with liraglutide relative to the placebo group.
Weight loss with liraglutide was maintained over 56 weeks and was similar regardless of the patient’s pre-diabetes status. In the liraglutide group, 14.4% of patients lost more than 15% of their body weight versus 3.5% in the placebo group. Overall, about 92% of those on liraglutide and 65% of those on placebo lost weight, according to the authors.
Systolic and diastolic blood pressure had decreased more in the liraglutide group at follow-up. For quality of life, liraglutide was associated with higher overall scores but lower scores when it came to the reported experience of adverse effects.
But side effects were significant in the new study. The most common adverse side effects were GI related, but 94% of them were mild or moderate in severity. Most of the nausea and vomiting occurred in the first 4 to 8 weeks of treatment.
In addition, there were 12 confirmed cases of pancreatitis, 11 of them in the liraglutide group. About half of these were associated with the gallstones.
Pi-Sunyer X, et al “A randomized, controlled trial of 3.0 mg of liraglutide in weight management” N Engl J Med 2015; 373(1): 11-22.