Jonatan Ising Bagger1, Jens Juul Holst1, Bolette Hartmann1, Birgitte Andersen1, Filip Krag Knop1, Tina Vilsbøll1. 1. Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
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/m(2); fasting plasma glucose 5.1 [4.4-5.4] mmol/L; and glycated hemoglobinA1c 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.
RCT Entities:
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/m(2); 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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