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

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

Glucagon‐like peptide‐1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta‐analysis and meta‐regression

“…Liraglutide had the most RCTs, with 30 studies. 14,15,24,33,35,37,38,41,42,45,48,49,51,52,54,56,[58][59][60][61][63][64][65]68,70,73,74,[76][77][78] There were 16 RCTs 16,17,19,22,26,[28][29][30][31]34,36,39,43,66,69,71 done for semaglutide and five for dulaglutide. 23,25,40,44,55 Exenatide had 12…”

New insights into the treatment of obesity

“…38 Evidently, the combination of exercise and pharmacotherapy reduces risk factors in people with obesity and thus increases their general health and quality of life. 42,43 Moreover, combining physical activity and antiobesity drug therapy effectively prevents weight regain. 44 Physical activity is considered a prerequisite for prescribing antiobesity medication.…”

“…The continuous use of orlistat, semaglutide, and the combination products phentermine/topiramate ER, and bupropion ER/naltrexone ER is recommended only with weight loss of at least 5% in the first 3 months of treatment 18 (or at least 4% at 16 weeks for liraglutide 41 ) and can be continued as long as treatment provides benefit and no serious adverse events occur 38 . Evidently, the combination of exercise and pharmacotherapy reduces risk factors in people with obesity and thus increases their general health and quality of life 42,43 . Moreover, combining physical activity and antiobesity drug therapy effectively prevents weight regain 44 .…”

Potent incretin‐based therapy for obesity: A systematic review and meta‐analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety

“…17 Importantly, exercise can effectively maintain dietinduced weight loss and improve body composition for at least 1 year. 18,19 Weight loss decreases energy expenditure, increases sedentary behavior, and may affect appetite 20,21 with observations of increased appetite at least a year after diet-induced weight loss in some studies, [22][23][24] which makes sustained weight loss difficult. For people with a BMI ≥30 kg/m 2 or ≥27 kg/m 2 with at least one obesity-related comorbidity who have not experienced sustained weight loss with lifestyle changes alone, the addition of pharmacotherapy as an adjunct to lifestyle intervention may be an option.…”

“…Exercise interventions typically result in modest weight losses of about 0 to 4 kg but with reduced fat mass and preserved lean mass, improving body composition 17 . Importantly, exercise can effectively maintain diet‐induced weight loss and improve body composition for at least 1 year 18,19 …”