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Randomized Controlled Trial
. 2023 Feb 25;22(1):41.
doi: 10.1186/s12933-023-01765-z.

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

Affiliations
Randomized Controlled Trial

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

Rasmus M Sandsdal et al. Cardiovasc Diabetol. .

Abstract

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.

Keywords: Cardiometabolic risk; Exercise; GLP-1; Inflammation; Metabolic syndrome; Obesity; Randomized clinical trial.

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Conflict of interest statement

RMS: Family member holds Novo Nordisk stocks. MR: Currently employed at Novo Nordisk. JJH: Advisory boards: Novo Nordisk. SM: Advisory boards: AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi Aventis. Lecture fees: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi Aventis. Grant Recipient: Novo Nordisk, Boehringer-Ingelheim. SST: Grant and lecture fee recipient, Novo Nordisk. JRL, CJ, CRJ, SBKJ, MBB, AFB, LG, JBJ, CA, BMS have no disclosures.

Figures

Fig. 1
Fig. 1
Observed MetS-Z before and after Low-calorie Diet and at Week 52 by Randomization Group. Observed MetS-Z of individual per-protocol participants (black dots) by randomization group at the three visits, before the low-calorie diet (week -8), after the low-calorie diet (week 0), and end of the trial (week 52), presented as box plots. Tops of the boxes indicate the upper quartile; bottom of the box is the lower quartile; white diamonds observed mean; black horizontal line medians; whiskers ± 1.5 times the interquartile range or highest or smallest observation. Box plots overlay MetS-Z quartiles associated with the risk of future diabetes [12] and coronary heart disease [13] compared to the first quartile and adjusted for individual MetS factors. For diabetes, unadjusted risks are also shown in parentheses. MetS-Z metabolic syndrome severity z-score. T2DM type 2 diabetes, CHD coronary heart disease
Fig. 2
Fig. 2
Changes During Low-calorie Diet and From Randomization to Week 52. Per-protocol analysis of mixed model estimated changes in metabolic syndrome severity z-score (A), metabolic syndrome prevalence (B), android fat percentage (C), and high-sensitivity C-reactive protein (D) during a low-calorie diet (shaded area; weeks -8 to 0) and treatment (weeks 0 to 52). Changes are estimated mean differences with ± standard error of the mean. Changes in high-sensitivity C-reactive protein are presented as percentages via ratios from back-transformed log-data and shown with 95% confidence intervals. Between-group changes are estimated mean differences with 95% confidence intervals and p-values. Results are adjusted for age group (< / ≥ 40 years) and sex. Dashed line is the baseline for the low-calorie diet and randomized groups (at week 0)

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