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首页> 外文期刊>Cell metabolism >The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes
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The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes

机译：双GIP / GLP-1受体Agonist，NNC0090-2746，2型糖尿病患者的持续效果

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摘要

Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1.8 mg of NNC0090-2746 or placebo subcutaneously once daily. Liraglutide 1.8 mg (Victoza), starting with 2-week dose escalation, was administered subcutaneously once daily as an open-label reference arm. Measurements were collected at regular intervals after randomization. NNC0090-2746 significantly improved glycemic control and reduced body weight compared with placebo. Total cholesterol, alone among a range of lipid parameters, and leptin were both significantly reduced compared with placebo. Treatment with NNC0090-2746 was generally safe and well tolerated.
机译：来自杂交胰高血糖素样肽1（GLP-1）和葡萄糖依赖性促胰岛素肽（GIP）序列的单分子双肠促胰岛素已在动物模型中证明了协同降低肥胖，并在短期人体试验中证明了协同降低高血糖。在这里，我们扩展了NNC0090-2746（也称为RG7697）的特性，这是一种脂肪酰化双激动剂，具有体外平衡的GIPR和GLP-1R兴奋性。在这项为期12周的随机、安慰剂对照、双盲2a期试验中，二甲双胍控制不充分的2型糖尿病患者每天皮下注射1.8 mg NNC0090-2746或安慰剂一次。利拉鲁肽1.8 mg（维克托萨），从2周剂量递增开始，作为开放标签对照组每天皮下注射一次。随机分组后定期收集测量数据。与安慰剂相比，NNC0090-2746显著改善血糖控制并减轻体重。与安慰剂相比，在一系列脂质参数中，总胆固醇和瘦素均显著降低。NNC0090-2746治疗通常是安全的，耐受性良好。

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