Murphy Enda, Finucane Francis Martin
Department of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.
Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland.
Int J Obes (Lond). 2025 Mar;49(3):427-432. doi: 10.1038/s41366-024-01499-2. Epub 2024 Mar 8.
We are at the start of an exciting new era of very effective pharmacotherapy for patients with obesity, with the latest generation of drugs approaching the efficacy of obesity surgery. Clinical trials of obesity drugs tend to emphasise the importance of participation in some form of structured lifestyle intervention for all trial participants. This usually consists of advice to reduce calorie intake and increase moderate to vigorous physical activity. There is strong evidence that structured lifestyle modification programmes improve health in patients with obesity and related disorders. However, there is no specific evidence that they improve the response to obesity medications. This is because of the way that drug trials for patients with obesity have traditionally been designed, with participants in the active drug treatment group being compared to participants on placebo drug treatment, but with both groups always receiving the same structured lifestyle intervention. While this approach is entirely reasonable, it makes it impossible to draw any inferences about the efficacy of structured lifestyle modification to augment the response to drug therapy. Given this genuine equipoise, a critical step in ensuring that our treatment of patients with obesity is robustly evidence-based is to determine whether "drug plus lifestyle" offer any advantage over "drug plus placebo" in large, well-designed and adequately powered clinical trials. We also need to determine the cost-effectiveness of these programmes.
我们正处于肥胖症患者有效药物治疗这一令人兴奋的新时代的开端，最新一代药物已接近肥胖症手术的疗效。肥胖症药物的临床试验往往强调所有试验参与者都要参与某种形式的结构化生活方式干预的重要性。这通常包括减少卡路里摄入量和增加适度至剧烈身体活动的建议。有强有力的证据表明，结构化的生活方式改变计划能改善肥胖症患者及相关疾病患者的健康状况。然而，没有具体证据表明这些计划能改善对肥胖症药物的反应。这是由于肥胖症患者药物试验的传统设计方式，即活性药物治疗组的参与者与接受安慰剂药物治疗的参与者进行比较，但两组始终接受相同的结构化生活方式干预。虽然这种方法完全合理，但却无法得出关于结构化生活方式改变对增强药物治疗反应的疗效的任何推论。鉴于这种真正的平衡，确保我们对肥胖症患者的治疗有充分证据支持的关键一步，是在大型、设计良好且有足够效力的临床试验中确定“药物加生活方式”是否比“药物加安慰剂”有任何优势。我们还需要确定这些计划的成本效益。
