Bastin Marie, Andreelli Fabrizio
Diabetology-Metabolism Department, Sorbonne Université, ICAN, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, F-75013, France.
Diabetes Metab Syndr Obes. 2019 Sep 30;12:1973-1985. doi: 10.2147/DMSO.S191438. eCollection 2019.
The need for efficient and safe therapy to improve such metabolic diseases as obesity and type 2 diabetes mellitus is currently unmet. The development of dual GIPR-GLP1R coagonists that bind to either one or the other receptor (sequence-mixed dual agonists) has emerged as an innovative therapeutic strategy for obesity and type 2 diabetes. Combined activation of both receptors may act synergistically providing additive effects on glucose and body weight in comparison of GLP1 analogues alone. Preclinical studies have confirmed that GIPR-GLP1R coagonists improve several hallmarks of metabolic syndrome, such as obesity, hyperglycemia, and dyslipidemia. These metabolic benefits have been translated from mice to nonhuman primates and humans. Recent clinical trials have shown that coagonists induce significant benefits on body weight, fasting, and postprandial glucose levels, insulin sensitivity, and total cholesterol. Combined GIP- and GLP1R activators have the potential to become a treatment option for patients with type 2 diabetes.
目前,对于改善肥胖症和2型糖尿病等代谢性疾病的高效、安全疗法的需求尚未得到满足。开发与其中一种或另一种受体结合的双GIPR - GLP1R激动剂(序列混合双激动剂)已成为治疗肥胖症和2型糖尿病的一种创新治疗策略。与单独使用GLP1类似物相比,两种受体的联合激活可能具有协同作用,对血糖和体重产生累加效应。临床前研究证实,GIPR - GLP1R激动剂可改善代谢综合征的几个特征,如肥胖、高血糖和血脂异常。这些代谢益处已从小鼠转化到非人灵长类动物和人类身上。最近的临床试验表明,双激动剂对体重、空腹和餐后血糖水平、胰岛素敏感性以及总胆固醇有显著益处。联合GIP和GLP1R激活剂有可能成为2型糖尿病患者的一种治疗选择。