《柳叶刀》：GLP-1减肥药与运动结合，停药后预防体重反弹效果更佳

Core Insights - The article discusses the significant impact of GLP-1 receptor agonists (GLP-1RAs) on obesity management, highlighting the challenge of weight rebound after discontinuation of medication [2] - A Danish randomized controlled trial indicates that incorporating supervised exercise during the treatment and withdrawal phases can significantly improve weight and body composition maintenance after one year [2] Research Design and Methodology - The trial included obese adults aged 18-65 with a BMI of 32-43 kg/m², progressing through three phases: - Induction phase (8 weeks): Strict low-calorie diet (~800 kcal/day), average weight loss of approximately 13.1 kg - Randomized maintenance phase (52 weeks): Participants were assigned to supervised exercise, liraglutide 3.0 mg/day, a combination of both, or a placebo - Follow-up phase (52-104 weeks): All interventions ceased at week 52, with assessments at week 104 for weight and body fat changes - The primary endpoint was weight change from randomization (week 0) to one year post-discontinuation (week 104), with secondary endpoints including percentage change in body fat [3] Key Findings and Evidence - The combination of supervised exercise and liraglutide showed a persistent advantage: one year post-discontinuation, the combination group had a lower weight (approximately -5.1 kg, statistically significant) and a significant decrease in body fat percentage (approximately -2.3 percentage points) compared to liraglutide alone [5] - Weight regain was more pronounced in the liraglutide-only group (approximately +6.0 kg) compared to the supervised exercise group (approximately +3.6 kg), indicating better stability in the exercise group [5] Body Composition and Functional Benefits - The combination group exhibited clearer reductions in body fat and waist circumference, with lean body mass increasing across all groups - Quality of life metrics indicated that the combination group outperformed the liraglutide-only group in energy/fatigue and physical function, while the supervised exercise group also showed improvements in energy/fatigue and pain [7] Mechanisms and Practical Implications - During the weight loss induction phase, the medication suppresses appetite and reduces intake, but after discontinuation, energy intake and appetite signals may revert to previous levels, leading to weight regain - Supervised exercise can enhance insulin sensitivity, increase resting energy expenditure, preserve lean body mass, and improve appetite regulation and psychological state, helping to establish a new energy balance during the withdrawal phase - Previous observations indicated that approximately 67% of weight loss achieved with semaglutide is regained after discontinuation, supporting the complementary relationship between medication and exercise [10] Conclusion - Obesity is a chronic and relapsing condition; while medications can effectively reduce weight, the long-term outcome depends on the ability to maintain exercise and lifestyle changes post-medication - Viewing supervised exercise as a long-term prescription, alongside medication and intensified during the withdrawal phase, is currently one of the most evidence-supported and feasible strategies [10]