Metabolism and Nutrition Research Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK.
Obes Rev. 2019 Jun;20(6):816-828. doi: 10.1111/obr.12841. Epub 2019 Apr 10.
We are facing a global epidemic of obesity and type 2 diabetes. Weight loss, in the context of obesity and type 2 diabetes, may improve glycaemic control and weight-related comorbidities, and in some cases, induce diabetes remission. Although lifestyle-based weight loss strategies may be initially successful, most are not effective long-term. There is an increasing need to consider pharmacological approaches to assist weight loss in diabetes-obesity. Older glucose-lowering agents may cause weight gain, whereas the newer drug classes, sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP-1 RAs), concomitantly target weight loss and glycaemic control. Clinical trial data suggest that both SGLT2i and GLP1 RAs cause a mean weight loss of approximately 2 to 3 kg but real-world evidence and clinical experience suggests a significant heterogeneity in the magnitude of the weight loss (GLP-1 RAs) or the magnitude of the actual weight loss is significantly less than anticipated (SGLT2i). Why do some individuals lose more weight than others in response to these pharmacological treatments? This review will first explore mechanisms by which body weight is regulated through control of energy balance and its dysregulation in obesity, and then consider how these mechanisms may be modulated therapeutically with SGLT2i and GLP1 RAs.
我们正面临着肥胖和 2 型糖尿病的全球流行。在肥胖和 2 型糖尿病的背景下，减肥可能改善血糖控制和与体重相关的合并症，在某些情况下还可诱导糖尿病缓解。虽然基于生活方式的减肥策略最初可能会成功，但大多数策略在长期内都无效。越来越需要考虑采用药理学方法来辅助肥胖型糖尿病患者减肥。较老的降糖药物可能会导致体重增加，而新型药物类别，即钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2i）和胰高血糖素样肽受体激动剂（GLP-1 RAs），则同时针对体重减轻和血糖控制。临床试验数据表明，SGLT2i 和 GLP1 RAs 均可使体重平均减轻约 2 至 3 公斤，但真实世界的证据和临床经验表明，体重减轻的幅度存在显著异质性（GLP-1 RAs），或者实际体重减轻的幅度明显小于预期（SGLT2i）。为什么有些人在接受这些药物治疗时比其他人减轻的体重更多？这篇综述首先将探讨通过控制能量平衡及其在肥胖症中的失调来调节体重的机制，然后考虑这些机制如何通过 SGLT2i 和 GLP1 RAs 进行治疗调节。
