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

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. [Display omitted] •NNC0090-2746 is a fatty-acylated GIP/GLP-1 dual agonist•NNC0090-2746 improved glucose control in type 2 diabetic patients•NNC0090-2746 also decreased body weight and total cholesterol•The effect of NNC0090-2746 was dependent on initial level of glucose control Frias et al. assessed the effects of NNC0090-2746, a unimolecular dual agonist derived from hybridized GLP-1 and GIP, in patients with T2DM. NNC0090-2746 was well tolerated and significantly improved glycemic control and reduced body weight compared with placebo. Maximum benefit was obtained by patients with the best baseline glycemic control.