Hon. Clinical Professor National Centre for Cardiovascular Prevention and Outcomes, UCL Institute of Cardiovascular Science, Nomura House, 1 St Martin's le Grand, London EC1A 4NP, UK.
Eur J Intern Med. 2021 Nov;93:13-20. doi: 10.1016/j.ejim.2021.04.024. Epub 2021 May 21.
There is a growing unmet need for more effective treatment of obesity and its complications. While current anti-obesity medications are effective and offer real clinical benefits over diet and lifestyle interventions, they cannot meet the levels of efficacy and reduction of hard endpoint outcomes seen with bariatric surgery. As knowledge on the control of body weight unravels, the complexity of this physiology opens the opportunity to new druggable targets. Currently, gut peptide analogues such as semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, and the dual agonist GLP-1 and gastric inhibitory polypeptide (GIP) tirzepatide are the furthest advanced in clinical development and seem likely to meet current regulatory requirements within the next year or so. However, current regulatory requirements are out of step with the efficacy of new compounds and concepts relating to obesity and its complications. Many other drugs in early development will target different pathways of energy balance, raising the possibility of drug combinations to maximise efficacy as for other chronic disease such as hypertension and diabetes. This will allow more complex and personalised guidelines to evolve.
对于肥胖及其并发症的治疗，目前存在着日益增长的未满足的需求，需要更有效的治疗方法。虽然目前的抗肥胖药物在饮食和生活方式干预方面有效，并提供了真正的临床益处，但它们无法达到减重手术所带来的疗效水平和硬终点结果的降低。随着对体重控制的认识不断深入，这种生理学的复杂性为新的可用药靶点开辟了机会。目前，肠道肽类似物如司美格鲁肽，一种胰高血糖素样肽-1（GLP-1）受体激动剂，以及双重激动剂 GLP-1 和胃抑制肽（GIP）替西帕肽，在临床开发中处于最先进的地位，似乎有可能在未来一年左右左右达到当前的监管要求。然而，目前的监管要求与肥胖及其并发症的新化合物和概念的疗效不符。许多处于早期开发阶段的其他药物将针对能量平衡的不同途径，提高药物联合使用的可能性，以最大限度地提高疗效，就像治疗高血压和糖尿病等其他慢性疾病一样。这将允许更复杂和个性化的指南的发展。
