The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes

被引：249

作者：

Frias, Juan Pablo ^{[1
]}

Bastyr, Edward J., III ^{[2
]}

Vignati, Louis ^{[3
]}

Tschoep, Matthias H. ^{[4
,5
,6
]}

Schmitt, Christophe ^{[7
]}

Owen, Klara ^{[8
]}

Christensen, Rune Haubo ^{[8
]}

DiMarchi, Richard D. ^{[9
]}

机构：

[1] Natl Res Inst, Los Angeles, CA 90057 USA

[2] Indiana Univ Sch Med, Div Endocrinol & Metab, Indianapolis, IN 46202 USA

[3] MB2 LLC, Carmel, IN 46032 USA

[4] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Inst Diabet & Obes, D-85764 Neuherberg, Germany

[5] Tech Univ Munich, Div Metab Dis, Dept Med, D-80333 Munich, Germany

[6] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany

[7] F Hoffmann La Roche & Cie AG, CH-4070 Basel, Switzerland

[8] Novo Nordisk AS, DK-2860 Soborg, Denmark

[9] Novo Nordisk Res Ctr Indianapolis, Indianapolis, IN 46241 USA

来源：

CELL METABOLISM | 2017年 / 26卷 / 02期

关键词：

GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; GIP RECEPTOR; CHEMICAL ABLATION; CONTROLLED-TRIAL; DOUBLE-BLIND; 7-36; AMIDE; GLUCOSE; INCRETIN;

D O I：

10.1016/j.cmet.2017.07.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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.

引用

页码：343 / +

页数：12

共 47 条

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