Combination liraglutide plus exercise improves weight-loss maintenance in obesity Leave a comment

Novo Nordisk supplied liraglutide and placebo injector pens; Cambridge Weight Plan supplied diet-replacement products for the low-calorie diet phase. Funding partners did not take part in the execution of the trial or interpretation of results. Torekov reports she has received a grant from the Novo Nordisk Foundation. Please see the study for all other authors’ relevant financial disclosures.

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A combination regimen of moderate to vigorous exercise plus daily liraglutide treatment resulted in better weight loss and improved weight maintenance compared with either treatment alone, according to data from a head-to-head trial.

Signe S. Torekov

“It is great news for public health that a significant weight loss can be maintained with exercise for approximately 115 minute per week performed mostly at vigorous intensity, such as cycling,” Signe S. Torekov, PhD, professor in the department of biomedical sciences at the University of Copenhagen, Denmark, told Healio. “By combining exercise with obesity medication, the effect is twice as good as each of the individual treatments.”

Exercise and 3 mg of daily liraglutide resulted in greater weight loss than either strategy alone after 1 year. Data were derived from Lundgren JR, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2028198.

In a randomized, head-to-head, placebo-controlled trial, Torekov and colleagues analyzed data from 215 adults with obesity (BMI range, 32-43 kg/m²) but without diabetes who followed a low-calorie diet of 800 kcal per day for 8 weeks. Participants who lost at least 5% of baseline body weight (n = 195; 64% women; mean age, 43 years) were then randomly assigned for 1 year to one of four strategies: a moderate- to vigorous-intensity exercise program plus placebo (exercise group; n = 49); treatment with subcutaneous liraglutide 3 mg daily (Saxenda, Novo Nordisk) plus usual activity (liraglutide group; n = 49); exercise program plus liraglutide therapy (combination group; n = 49); or placebo plus usual activity (placebo group; n = 49). Endpoints with prespecified hypotheses were change in body weight and change in body fat percentage from randomization to the end of the treatment period in the intention-to-treat population. The findings were published in The New England Journal of Medicine.

Combination therapy boosts maintenance

After the 8-week low-calorie diet, 195 participants experienced a mean decrease in body weight of 13.1 kg. The mean weekly duration of exercise was 118 minutes at an intensity of 78% of the maximum heart rate in the exercise group and 111 minutes at an intensity of 79% of the maximum heart rate in the combination group.

At 1 year, all active treatment strategies led to greater weight loss vs. placebo. Mean differences were 4.1 kg for the exercise group (95% CI, 7.8 to 0.4); 6.8 kg for the liraglutide group (95% CI, 10.4 to 3.1) and 9.5 kg for the combination group (95% CI, 13.1 to 5.9).

The combination strategy led to greater weight loss than exercise (difference, 5.4 kg; 95% CI, 9 to 1.7) but not liraglutide (difference, 2.7 kg; 95% CI, 6.3 to 0.8). The combination strategy decreased body fat percentage by 3.9 percentage points, which was approximately twice the decrease in the exercise group (1.7 percentage points; 95% CI, 3.2 to 0.2) and the liraglutide group (1.9 percentage points; 95% CI, 3.3 to 0.5).

The researchers found that only the combination strategy was associated with improvements in HbA1c, insulin sensitivity and cardiorespiratory fitness.

“After 1 year, the group with exercise alone and the group with obesity medication alone maintained the weight loss of 13 kg and health improvements,” Torekov told Healio. “The most dramatic improvements occurred in the combination group, which followed the exercise program and received obesity medication. The researchers observed additional weight loss in this group, and the total weight loss was approximately 16 kg over 1 year. The health benefits were also double that of each of the single treatments, ie, twice the loss of fat mass while preserving muscle mass, higher fitness ratings, reduced blood sugar and improved quality of life.”

Exercise strategy ‘feasible’

Torekov said participants in the placebo group gained half of the weight lost back, along with deterioration of all risk factors, including development of type 2 diabetes and cardiovascular disease.

The researchers noted that a major strength of this trial was the “structured but flexible” exercise program with rigorous monitoring of exercise adherence.

“Our trial showed that 1 year of mostly vigorous-intensity exercise, performed approximately 2.4 times per week, as a weight-loss maintenance strategy was feasible in persons with obesity with a very low initial level of fitness,” the researchers wrote. “The finding that the 1-year trajectories with regard to body weight, waist-to-hip ratio and adherence were stable in the exercising groups — in which participants had a loss of fat mass and increase in lean mass, along with improved emotional well-being — also support feasibility.”

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Signe S. Torekov, PhD, can be reached at

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