Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial

Cardiovascular Diabetology

Research

Mads Rosenkilde¹  Charlotte Janus¹  Adrian F. Bogh¹  Signe S. Torekov¹  Simon B. K. Jensen¹  Bente M. Stallknecht¹  Rasmus M. Sandsdal¹  Julie R. Lundgren¹  Christian R. Juhl¹  Jens J. Holst²  Jens-Erik B. Jensen³  Sten Madsbad⁴  Charalambos Antoniades⁵  Martin B. Blond⁶  Lasse Gliemann⁷ 

[1] Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen N, Denmark;Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen N, Denmark;Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark;Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark;Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK;Steno Diabetes Center Copenhagen, Gentofte, Denmark;The August Krogh Section for Human Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;

关键词: Metabolic syndrome;    Obesity;    Inflammation;    Cardiometabolic risk;    GLP-1;    Exercise;    Randomized clinical trial;   

DOI  :  10.1186/s12933-023-01765-z

 received in 2022-10-04, accepted in 2023-02-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundIdentifying 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.MethodsThis 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.ResultsThe 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).ConclusionThe 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

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 2

Fig. 5