Discussion
obesity, mass loss, inflammation, cardiometabolic disease, diet-induced reductions, abdominal obesity, metabolic syndrome, reduced fasting glucose, weight loss
OBESITY, INFLAMMATION, METABOLIC SYNDROME, METABOLIC SYNDROME
Identifying and managing the risk of cardiometabolic disease associated with obesity remains a major healthcare challenge. Metabolic syndrome, abdominal obesity, and low-grade inflammation constitute risk factors for future cardiometabolic disease. Therefore, we investigated improvements in metabolic syndrome, abdominal obesity, and low-grade inflammation during exercise, a glucagon-like peptide 1 receptor agonist, or the combination of the two following an eight-week low-calorie diet.The diet-induced weight loss reduced MetS-Z, abdominal obesity, and inflammation marker hsCRP. After one year, the combination of exercise and liraglutide treatment reduced MetS-Z, android fat percentage, and hsCRP compared to placebo. Exercise treatment maintained MetS-Z and hsCRP and reduced android fat percentage compared to placebo. Liraglutide treatment reduced Mets-Z and android fat percentage while maintaining hsCRP compared to placebo. Placebo treatment was associated with maintenance of the diet-induced reductions in MetS-Z, hsCRP, and android fat percentage, even though 50% of the weight lost during the low-calorie diet was regained in the placebo group, while MetS prevalence and fat masses increased again. In addition, we have previously reported that the placebo group became sedentary one year after the initial weight loss [Large reductions in MetS-Z, abdominal obesity, and hsCRP compared to placebo were seen in the combination group, providing large potential reductions in cardiometabolic risk. Furthermore, the combination group showed a reduction of android fat percentage that was about twice as large as the reduction seen in both the exercise and liraglutide groups, underlining the complementary effects of combined treatment.Liraglutide treatment alone further reduced MetS-Z following the diet-induced reductions, largely due to reduced fasting glucose, an expected effect of liraglutide treatment [If the comparative risks, illustrated in Fig. The combination group reduced body weight due to fat mass loss with a preferential reduction of android fat rather than gynoid fat. Thus, during the entire trial, abdominal obesity of participants in the combination group was reduced by almost 8%-points while maintaining total lean mass. This finding contrasts with other weight loss strategies, including the low-calorie diet used in this trial, which often lead to large amounts of lost lean mass (e.g., 20–50% lost by bariatric surgery, 30–47% by GLP-1 RA treatment before weight loss) [The liraglutide group reduced android fat percentage without changing body weight, suggesting a reduction of android fat percentage independent of weight loss. This is consistent with recent findings from a 36-week study examining changes to visceral fat estimated by magnetic resonance imaging in response to treatment with liraglutide [Despite similar reductions in android fat in the exercise and liraglutide group, exercise did not significantly decrease hsCRP after one year. However, studies that demonstrate reduced inflammation as an effect of exercise do often not have an initial weight loss phase [In a clinical setting, hsCRP levels higher than 3 mg/L indicate increased cardiovascular risk [A strength of this study is the longitudinal, randomized, placebo-controlled design with four separate groups to assess single and combined effects of treatments with exercise and liraglutide 3.0 mg/day. Another strength is the novelty of analyzing the effects of maintained interventions on a clinically relevant continuous metabolic syndrome score combined with assessments of abdominal obesity and inflammation, translating to potential cardiometabolic risk.In this study, we present the findings from the participants who completed the trial according to the prescribed interventions to better observe the effects of actually performed exercise, often confounded by inadequate adherence [