Different doses of liraglutide, an investigational human glucagon-like peptide-1 analogue developed to treat type 2 diabetes, were associated with significantly greater weight loss when compared with orlistat and placebo in a European multicenter study of over 500 obese adults who did not have type 2 diabetes.
“Overall, the results of this study indicate the potential benefit of liraglutide, in conjunction with an energy-deficit diet, in the treatment of obesity and associated risk factors,” according to the investigators lead by Dr. Arne Astrup of the University of Copenhagen, Denmark. Liraglutide, which stimulates the release of insulin when serum glucose levels are elevated, “offers a new mode of action for the treatment of obesity and improved efficacy compared with currently available therapies,” they said, noting that the long-term risk/benefit profile and the effect on maintaining weight must be established.
Liraglutide, which is under review by the Food and Drug Administration as a treatment for type 2 diabetes, has been associated with a dose-dependent weight loss, which the authors said is “most probably” due to a combination of effects on the GI tract and brain, since “native [glucagon-like peptide-1 (GLP-1)] suppresses appetite and energy intake in both normal-weight and obese individuals,” the authors said.
The study was funded by liraglutide manufacturer, Novo-Nordisk A/S. Dr. Astrup has been paid for lectures and has conducted sponsored research for the company. All authors reported performing commercially sponsored research for and advising Novo Nordisk, as well as competitive manufacturers. Two authors are employees of the company.
In the double-blind, placebo-controlled study, individuals ages 18-65, with body mass index ranging from 30 to 40 kg/m
After 20 weeks, the individuals on liraglutide lost a mean of 4.8 kg to 7.2 kg, compared with a mean of 2.8 kg among those on placebo and 4.1 kg among those on orlistat. The differences between all doses of liraglutide and placebo were significant.
In addition, 61% of those on liraglutide lost more than 5% of their body weight, which was significantly greater than those on placebo, and 76% of those on 3.0 mg of liraglutide lost more than 5% of their weight, when compared with 30% of those on placebo and 44% of those on orlistat, all significant differences.
Those on all doses of liraglutide saw reductions in blood pressure, and the prevalence of prediabetes was reduced by 84%-96% among those on the different doses of liraglutide. Weight loss was associated with reduced waist circumference, lowered systolic and diastolic blood pressure, and the proportion of patients with metabolic syndrome and prediabetes.
Overall, liraglutide was well tolerated, the investigators wrote. Having to self-administer injections did not appear to affect compliance, and while those on liragltuide experienced a higher rate of nausea and vomiting than did those on placebo, it was transient and mild to moderate for the most part.
In an editorial, Dr. George Bray of Louisiana State University, Baton Rouge, said that a limitation to using peptides like liraglutide for treating obesity is that they have to be injected, and “whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established.” But he added, “from what we do know about GLP-1 agonists and their mechanisms, we can be optimistic that their promise for the treatment of obesity will be fulfilled.” Dr. Bray disclosed no conflicts of interest.