Acute concomitant glucose-dependent insulinotropic polypeptide receptor antagonism during glucagon-like peptide 1 receptor agonism does not affect appetite, resting energy expenditure or food intake in patients with type 2 diabetes and overweight/obesity

AIMS: When combined with glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, antagonising the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) reduces body weight in rodent models of obesity. Here, we investigated the acute effects of GIPR antagonism combined with a GLP-1 infusion on determinants of body weight in patients with type 2 diabetes and overweight/obesity.

MATERIALS AND METHODS: In a randomised, double-blind, placebo-controlled, crossover design, human synthetic GLP-1(7-36)NH2 (0.75 pmol/kg/min) was infused together with the selective GIPR antagonist GIP(3-30)NH2 (1,200 pmol/kg/min) or placebo for 320 minutes on two separate days covering an initial oral liquid mixed meal test and a terminal ad libitum meal. Appetite sensations, resting energy expenditure (REE) and food intake were evaluated, and subcutaneous adipose tissue (SAT) biopsies were analysed for triglyceride content.

RESULTS: Ten patients with type 2 diabetes and overweight/obesity (mean±SD; HbA1c 52±9 mmol/mol (7±1%); BMI 32.5±4.8 kg/m2 ) were included. Compared to placebo, infusion of the GIPR antagonist GIP(3-30)NH2 added to a GLP-1 infusion had no effect on appetite sensations, REE, food intake, or SAT triglyceride content during an ad libitum meal. Compared to placebo, GIP(3-30)NH2 lowered plasma glucagon by -12.4±5.9% (p=0.037), and reduced serum insulin by -32.5±8.0% (p=0.027).

CONCLUSIONS: During short term infusion, we found no effect of GIPR antagonism added to GLP-1R agonism on appetite sensations, REE, SAT triglyceride content or food intake in patients with type 2 diabetes and overweight/obesity. This article is protected by copyright. All rights reserved.