Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, is an effective weight loss agent in non-diabetics, according to a new study. The drug was approved last year for long-term treatment of obesity (Saxenda) and previous to that for the treatment of type 2 diabetes (Victoza). In this new study, 3731 non-diabetic patients with a BMI of at least 30, or at least 27 with dyslipidemia or hypertension, were randomized in a 2:1 ratio to liraglutide 3.0 mg subcutaneously once a day or placebo. Both groups received counseling on lifestyle modification. By week 56, patients in the liraglutide group lost a mean of 8.4 ± 7.3 kg body weight, while those in the placebo group lost a mean 2.8 ± 6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P < 0.001).

Almost two-thirds of patients in the liraglutide group lost at least 5% body weight compared to 27% of the placebo group (P < 0.001), and 33% and 10.6%, respectively, lost more than 10% body weight (P < 0.001).

The most frequent adverse effects with liraglutide were nausea and diarrhea, occurring in 6.2% of the treatment group and 5% of the placebo group. HgbA1c levels, fasting glucose, and fasting insulin levels were also lower in the treatment group, and both systolic and diastolic blood pressures were also lower in the treatment group. Patients in the liraglutide group also reported higher scores on assessment of overall physical and mental health. Pancreatitis was about five times more common in the liraglutide group, with an incidence of 0.4 events per 100 patient-years at risk. There was also a slightly higher incidence of breast cancer in the treatment group, although there was no evidence of thyroid cancer — a concern that has been raised regarding GLP-1 mimetics based on rat data.

The authors conclude that 3.0 mg of liraglutide given subcutaneously once daily as an adjunct to diet and exercise was associated with clinically meaningful weight loss, along with reductions in glycemic variables and multiple cardiometabolic risk factors (N Engl J Med 2015; 373:11-22DOI: 10.1056/NEJMoa1411892).