Physicians' Academy for Cardiovascular Education

Benefits diabetic patients with dual GIP/GLP-1 receptor agonist

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

Literature - Frias JP, Bastyr EJ 3rd, Vignati L, et al. - Cell Metab. 2017 Aug 1;26(2):343-352.e2


GLP-1 and glucose-dependent insulinotropic peptide (GIP) are gut hormones secreted from intestinal L cells and K cells, respectively, which account for most of the incretin effect in healthy adults [1]. So far, clinical research has focused on GLP-1, with much less attention given to GIP, due to data reporting promoted obesity and impaired lipid metabolism in animals by GIP [2]. Moreover, single-dose trials of GIP in type 2 diabetes mellitus (T2DM) patients, showed a worsening of postprandial hyperglycemia [3].

However, recent data support the hypothesis that the two incretins may complement one another, due to their ability to further decrease blood glucose and body weight when compared with peptides functioning by just one of the two mechanisms.

NNC0090-2746 (previously developed as RG7697) is a fatty-acylated GIP/GLP-1 dual agonist in clinical development for the treatment of T2DM [4]. In this phase 2a, multi-center, randomized, double-blind, parallel-group, placebo-controlled trial with open-label comparison study, the effects of NNC0090-2746 on glycemic control, body weight and other metabolic parameters were evaluated in T2DM patients, inadequately controlled with metformin (HbA1c ≥7.2% and ≤10.5%). For this purpose, 108 patients who were able to perform the self-injections satisfactorily were randomized into the 12-week double-blind treatment period in a 1:1:1 manner to NNC0090-2746, placebo or liraglutide 1.8 mg with a 2-week dose escalation. Primary endpoint was HbA1c change from baseline to week 8 and secondary/exploratory endpoints were evaluated at week 12 or 13.

Main results


In 108 T2DM patients inadequately controlled with metformin, NNC0090-2746 significantly improved glycemic control and reduced body weight, total cholesterol and leptin levels, compared with placebo. The treatment with NNC0090-2746 was generally safe and well tolerated. These data suggest that integrated GIP agonism may offer additional benefits on weight loss and total cholesterol.


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