Most patients were able to keep the weight off for the duration of the 56-week study on the drug marketed as Saxenda by Novo Nordisk, according to the findings published in the New England Journal of Medicine.
The randomized, controlled trial was conducted at 191 sites in 27 countries in Europe, North America, South America, Asia, Africa and Australia.
Patients in the study were 18 and older and each had a body mass index of 30 or higher.
BMI is calculated by weight in kilograms divided by the square of the height in meters. The healthy range for most people is 19-25 BMI.
Of the 3,731 people in the study, about two thirds were given the drug plus training to improve their lifestyle habits, and the rest followed the same lifestyle intervention but were given a placebo.
The trial was double-blind, meaning that neither patients or doctors knew if they were dealing with the real drug or the placebo.
Those who received the drug were given a higher dose (three milligrams) than is prescribed for diabetes patients (1.8 milligrams), and were injected with the drug under the skin daily.
People in the placebo group lost an average of six pounds. Those who were given the drug averaged about three times more weight loss.
A total of 63 percent of those in the liraglutide group lost at least five percent of their body weight, compared to 27 percent in the placebo group.
Kevin Williams, chief of endocrinology, diabetes and metabolism at Temple University Health, described the weight loss in the liraglutide group as "significant."
Williams was not involved in the study.
Side effects included gastrointestinal distress, gallstones and a slight increase in breast cancer risk.
Researchers said more study is needed on the breast cancer findings, and said it was possible that weight loss enabled more tumors to be found.
"This is another approach in tackling the obesity epidemic in our country," said Elias Siraj, director of the Diabetes Program at Temple University Hospital, who along with Williams penned an accompanying editorial in the journal.
"Fortunately, even modest weight loss of five percent to 10 percent makes nearly all medical issues more manageable."
Liraglutide has been used at a lower dose for treating diabetes in recent years, and some patients noticed it appeared to help them lose weight.
About 35 percent of adult Americans, or about 100 million people, live with obesity.
Two other anti-obesity drugs were launched in the United States in 2012, but the treatments carry side effects and are not widely used.