Physicians' Academy for Cardiovascular Education

Weight loss maintenance in obesity more effective with GLP-1RA and exercise than either treatment alone

Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined

Literature - Lundgren JR, Janus C, Jensen SBK, et al. - N Engl J Med. 2021;384:1719-1730. doi: 10.1056/NEJMoa2028198.

Introduction and methods

Weight regain after weight loss is a major problem in the treatment of individuals with obesity. The GLP-1RA liraglutide is used in the treatment of obesity. It induces weight loss and maintains diet-induced weight loss for at least 1 year primarily due to a suppressed appetite [1-6]. Diet management or structured exercise programs can also sustain weight loss, as well as lifestyle interventions that simultaneously encourage calorie restrictions and increase physical activity [1, 7-14]. However, which strategy is most effective in the prevention of weight gain after weight loss has not been assessed thoroughly.

This study assessed the efficacy of 1-year treatment with a moderate-to-vigorous intensity exercise program, liraglutide treatment at a dose of 3 mg per day, or the combination of exercise with liraglutide compared to placebo for the maintenance of a healthy diet-induced weight loss in individuals with obesity

This investigator-initiated, randomized, head-to-head, placebo-controlled trial included individuals with obesity (32-43 kg/m²) without diabetes. Individuals followed a low-calorie diet of 800 kcal per day for 8 weeks (pre-randomization phase). Only participants (n=195) who had achieved a weight loss of ≥5% of their baseline body weight were randomized (1:1:1:1) to the 1) exercise group (placebo plus exercise), 2) liraglutide group (liraglutide plus usual activity), 3) combination group (liraglutide plus exercise), or 4) placebo group (placebo plus usual activity). Exercise was defined as a minimum of 150 minutes per week of moderate-intensity or 75 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination of both. The primary endpoint was change in body weight from randomization to week 52. Secondary outcome was change in body-fat percentage. Also prespecified metabolic health-related end points and safety were investigated. Participants remained in the trial if the use of liraglutide or placebo was discontinued.

Main results


This trial demonstrated that a combination strategy of exercise and liraglutide treatment was more effective in maintaining healthy diet-induced weight loss after 1 year than either liraglutide or exercise alone in individuals with obesity and without diabetes. The placebo group showed an increase in body weight and body-fat percentage compared to the other three treatment groups.


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Find this article online at N Eng J Med.

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