People with obesity who combine moderate to vigorous intensity exercise with liraglutide treatment after diet-induced weight loss may have more effective maintenance of healthy weight loss compared with either exercise or liraglutide alone, according to research published in The New England Journal of Medicine.

A team of investigators conducted a randomized, head-to-head, placebo-controlled trial (S-LITE; Identifier: NCT04122716) to determine the efficacy of a 1-year moderate to vigorous exercise program, liraglutide treatment (3.0 mg per day), or the combination of both, compared with placebo, for the maintenance of healthy weight loss following weight loss due to a low-calorie diet.

A total of 195 individuals with obesity who did not have diabetes and took part in an 8-week low-calorie diet were randomly assigned for a year to either a moderate to vigorous exercise program plus placebo (exercise group), treatment with liraglutide plus usual activity (liraglutide group), exercise program and liraglutide therapy (combination group), or placebo with usual activity (placebo group). Endpoints measured the change in body weight and body-fat percentage from randomization to end of treatment duration in the intention-to-treat groups.

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After the 8-week low-calorie diet, participants had a mean decrease of 13.1 kg in body weight. All of the active treatment groups had a greater weight loss at 1 year than placebo, with a -4.1 kg difference in the exercise group (P =.03), -6.8 kg difference in the liraglutide group (P <.001), and a -9.5 kg difference in the combination group (P <.001).

Compared with the exercise cohort, participants in the combination cohort had a greater weight loss (P =.004); however, combination treatment did not lead to greater weight loss than liraglutide alone (P =.13). The combination cohort experienced a body-fat percentage decrease by 3.9 percentage points, which was nearly twice the decrease of the exercise group (P =.02) and the liraglutide group (P =.009).

Of the 4 groups, improvements in glycated hemoglobin levels, insulin sensitivity, and cardiorespiratory fitness were all only associated with combination therapy. Compared with the combination therapy group, increased heart rate and cholelithiasis were more often reported among participants in the liraglutide group.

“Both the liraglutide group and the combination group had further reductions in the glycated hemoglobin level, which is generally considered to reduce the risk of new-onset diabetes,” the authors noted.

“By contrast, the exercise group and the combination group were observed to have increased the participants’ cardiorespiratory fitness at a magnitude that has been associated with a decreased risk of cardiovascular disease and decreased all-cause mortality, and these strategies also maintained improvements in general and emotional health,” wrote the investigators.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Lundgren JR, Janus C, Jensen SBK, et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med. 2021;384(18):1719-1730. doi:10.1056/NEJMoa2028198

This article originally appeared on Gastroenterology Advisor