Effect of Oxyntomodulin, Glucagon, GLP-1, and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite, and Resting Energy Expenditure

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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:

We wanted to delineate the contributions of separate and combined GLP-1 receptor and 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.

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