Exercise and Liraglutide Reduces Metabolic Syndrome Severity in Adults With Obesity

Patients with obesity will benefit from treatment of liraglutide, exercise, and a low calorie diet in reducing the risk of cardiometabolic syndrome.

Combined exercise and glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment, liraglutide, reduced the severity of metabolic syndrome, abdominal obesity, and inflammation according to study results published in Cardiovascular Diabetology.

Researchers sought to identify and reduce cardiometabolic risk in patients with obesity. A randomized, double-blinded, placebo-controlled trial was conducted in Denmark from August 2016 to November 2019. Included in the study were participants with obesity aged 18 to 65 years old. Obesity was defined as a body mass index of 32 to 43 kg/m2. Participants with chronic comorbid conditions, including diabetes, were excluded. A total of 215 participants were enrolled in the study, of which 195 completed a low calorie diet for 8 weeks. The primary endpoint was total body weight and secondary endpoint was total body fat percentage.

Participants who completed the low calorie diet (N=195) were divided into 4 treatment arms for 1 year of treatment: placebo (n=49), moderate to vigorous exercise (n=48), liraglutide therapy (n=49), or a combination of exercise and liraglutide (n=49).

Exercise was defined as a minimum of 150 minutes per week of moderate-intensity exercise or 75 minutes per week of vigorous physical activity. Metabolic syndrome was measured with the metabolic syndrome severity z-score (MetS-Z), abdominal obesity was measured by android fat via dual-energy X-ray absorptiometry, and inflammation was measured with high-sensitivity C-reactive protein (hs-CRP). 

At inclusion, the mean MetS-Z score for participants was in the top third and bottom fourth quartiles of the reference population, indicating a high risk of cardiometabolic disease. After the diet, the MetS-Z score decreased to the second and third quartiles indicating a lower risk of diabetes and heart disease (0.52 to 0.06, P =.001). The number of participants with hypertension and prediabetes in the study population also decreased from 62% to 33% and 45% to 15%, respectively. Android fat percentage decreased by 2.9% (P <.001) and median hs-CRP decreased by 32% (P <.001) after the diet. 

The combination treatment thereby reduced all outcomes compared to placebo, potentially providing the largest risk reductions of future cardiometabolic disease in an adult population with obesity.

The researchers were only able to collect follow-up data for 130 patients due to drop out (placebo=39; exercise=26; liraglutide=36; and combination=29). A year after the 8 week diet, there were no changes observed in the placebo and exercise group MetS-Z scores. Among participants in the liraglutide group, MetS-Z scores decreased by 0.37 (P =.001), and among participants in the combined liraglutide and exercise intervention  group, that number decreased by 0.48 (P =.001).

The researchers noted that android fat percentages were unchanged in the placebo group, but observed a 2.6% reduction in android fat (P =.022) in the exercise group, a 2.8% reduction (P =.006) in the liraglutide group, and a 6.1% reduction in the combination group (P <.001) when compared to the placebo group. The hs-CRP remained unchanged in the placebo and exercise groups and decreased only in the combination group by 43% compared to the placebo (P =.030). 

Limitations of this study include the possibility of selection bias due to the high demands of the per-protocol requirements, including time spent on exercise as a major barrier. 

The researchers concluded that “The combination treatment thereby reduced all outcomes compared to placebo, potentially providing the largest risk reductions of future cardiometabolic disease in an adult population with obesity.”


Sandsdal RM, Juhl CR, Jensen SB, et al. Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial. Cardiovasc Diabetol. 2023;22(1):41. doi:10.1186/s12933-023-01765-z