TY - JOUR

T1 - Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation

T2 - a randomized controlled trial

AU - Sandsdal, Rasmus M

AU - Juhl, Christian R

AU - Jensen, Simon B K

AU - Lundgren, Julie R

AU - Janus, Charlotte

AU - Blond, Martin B

AU - Rosenkilde, Mads

AU - Bogh, Adrian F

AU - Gliemann, Lasse

AU - Jensen, Jens-Erik Beck

AU - Antoniades, Charalambos

AU - Stallknecht, Bente M.

AU - Holst, Jens J.

AU - Madsbad, Sten

AU - Torekov, Signe S

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - Background: Identifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss.Methods: This was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model.Results: The diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (- 0.37, 95% CI - 0.58 to - 0.16, P < 0.001) and the combination treatment (- 0.48, 95% CI - 0.70 to - 0.25, P < 0.001) compared to placebo. Abdominal fat percentage decreased by 2.6, 2.8, and 6.1 percentage points in the exercise, liraglutide, and combination groups compared to placebo, respectively, and hsCRP decreased only in the combination group compared with placebo (by 43%, P = 0.03).Conclusion: The combination of adherent exercise and liraglutide treatment reduced metabolic syndrome severity, abdominal obesity, and inflammation and may therefore reduce cardiometabolic risk more than the individual treatments. Trial registration: EudraCT number: 2015-005585-32, ClinicalTrials.gov: NCT04122716.

AB - Background: Identifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss.Methods: This was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model.Results: The diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (- 0.37, 95% CI - 0.58 to - 0.16, P < 0.001) and the combination treatment (- 0.48, 95% CI - 0.70 to - 0.25, P < 0.001) compared to placebo. Abdominal fat percentage decreased by 2.6, 2.8, and 6.1 percentage points in the exercise, liraglutide, and combination groups compared to placebo, respectively, and hsCRP decreased only in the combination group compared with placebo (by 43%, P = 0.03).Conclusion: The combination of adherent exercise and liraglutide treatment reduced metabolic syndrome severity, abdominal obesity, and inflammation and may therefore reduce cardiometabolic risk more than the individual treatments. Trial registration: EudraCT number: 2015-005585-32, ClinicalTrials.gov: NCT04122716.

KW - Faculty of Science

KW - Metabolic syndrome

KW - Obesity

KW - Inflammation

KW - Cardiometabolic risk

KW - GLP-1

KW - Exercise

KW - Randomized clinical trial

U2 - 10.1186/s12933-023-01765-z

DO - 10.1186/s12933-023-01765-z

M3 - Journal article

C2 - 36841762

VL - 22

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

IS - 1

M1 - 41

ER -