Prolonged Glucagon Infusion Does Not Affect Energy Expenditure in Individuals with Overweight/Obesity: A Randomized Trial

Obesity (Silver Spring). 2021 Jun;29(6):1003-1013. doi: 10.1002/oby.23141.


Objective: The aim of this study was to determine the effects of prolonged (72 hours) glucagon administration at a low dose (LD) (12.5 ng/kg/min) and high dose (HD) (25 ng/kg/min) on energy expenditure (EE) in healthy individuals with overweight or obesity.

Methods: Thirty-one healthy participants with overweight or obesity (BMI of 27-45 kg/m2 , 26-55 years old, 23 females) were randomized into LD, HD, or placebo groups and underwent 72-hour intravenous infusion of glucagon. Whole-room calorimetry was used to assess EE and substrate use during five overnight stays (2 days at baseline, 3 days of infusion) and during two 24-hour stays (baseline vs. day 3). Blood was sampled at regular intervals throughout the inpatient stay and analyzed for glucagon and biomarkers of metabolism.

Results: HD infusion elevated plasma glucagon levels compared with the placebo and LD infusion (P < 0.001). Sleeping, basal, and 24-hour EE was not significantly different among groups at any time point. Those receiving HD had significantly higher basal fat oxidation (Fat Ox) at days 2 and 3 than those receiving the placebo (P < 0.05); however, no differences in 24-hour Fat Ox were observed among groups (baseline vs. day 3).

Conclusions: An HD plasma glucagon infusion over 72 hours does not increase any aspects of EE in healthy individuals with overweight or obesity.

Trial registration: NCT03139305.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calorimetry
  • Drug Administration Schedule
  • Energy Metabolism / drug effects*
  • Female
  • Glucagon / administration & dosage*
  • Glucagon / pharmacology
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Overweight / metabolism*
  • Oxidation-Reduction / drug effects
  • Time Factors


  • Glucagon

Associated data