Sattar Naveed, Lee Matthew M Y
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Lancet Diabetes Endocrinol. 2025 Apr;13(4):347-354. doi: 10.1016/S2213-8587(24)00363-2. Epub 2025 Jan 24.
The extent to which newer, incretin-based drugs for obesity improve disease outcomes via weight loss versus the direct effects of these drugs is the subject of intense interest. Although reductions in major adverse cardiovascular events appear to be predominantly driven by the direct tissue effects of such drugs, the associated weight loss effects must be relevant to the benefits observed in other major outcomes, albeit to differing extents. In this Personal View, we draw on evidence to support that weight loss is at least partly responsible (albeit to differing extents) for the reported benefits of incretin-based drugs for obesity in people living with heart failure with preserved ejection fraction, hypertension, chronic kidney disease, and type 2 diabetes. Concurrently, we propose that drug-induced weight loss is largely responsible for the reported improvements in osteoarthritis, obstructive sleep apnoea, and metabolic dysfunction-associated steatohepatitis outcomes. However, more evidence is needed to solidify these observations, including, when possible, trials comparing the effects of incretin-based drugs for obesity with calorie-reduced diets on both outcomes and mechanistic pathways. Such evidence has implications for public health and the design of future trials of novel drugs for obesity.
新型的基于肠促胰岛素的肥胖治疗药物通过减重改善疾病预后的程度，与这些药物的直接作用相比，是人们极为关注的话题。尽管主要不良心血管事件的减少似乎主要由这类药物的直接组织效应驱动，但相关的减重效应必然与在其他主要结局中观察到的益处相关，尽管程度不同。在这篇个人观点文章中，我们利用证据支持，对于射血分数保留的心力衰竭、高血压、慢性肾脏病和2型糖尿病患者，减重至少在一定程度上（尽管程度不同）是基于肠促胰岛素的肥胖治疗药物所报告益处的原因。同时，我们提出药物诱导的减重很大程度上是骨关节炎、阻塞性睡眠呼吸暂停和代谢功能障碍相关脂肪性肝炎结局所报告改善的原因。然而，需要更多证据来巩固这些观察结果，包括在可能的情况下，进行比较基于肠促胰岛素的肥胖治疗药物与低热量饮食对结局和作用机制途径影响的试验。这些证据对公共卫生和未来肥胖新药试验的设计具有重要意义。
