Effect of oxyntomodulin, glucagon, GLP-1, and combined glucagon +GLP-1 infusion on food intake, appetite, and resting energy expenditure

Abstract

Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive. Objective:Wewantedto delineate the contributions of separateandcombinedGLP-1 receptorand glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin. Design: This was a double-blinded, randomized, crossover study. Setting: The study was conducted at a specialized research unit. Participants: Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m2; fasting plasma glucose 5.1 [4.4 -5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol). Interventions: Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol × kg-1 × min-1), glucagon (0.86 pmol × kg-1 × min-1), oxyntomodulin (3 pmol × kg-1 × min-1), or glucagon+GLP-1 (same doses). Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake. Results: Oxyntomodulin, GLP-1, and GLP-1+ glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline. Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.