Prolonged Glucagon Infusion Does Not Affect Energy Expenditure in Individuals with Overweight/Obesity: A Randomized Trial
Abstract
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/m 2, 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.
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In animal models, glucagon stimulates energy expenditure through activation of brown adipose tissue, but the significance of this effect has not been confirmed by human data.
“In animal models, glucagon stimulates energy expenditure through activation of brown adipose tissue [68], although the significance of this effect has not been confirmed by human data [69].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [69]
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“In animal models, glucagon stimulates energy expenditure through activation of brown adipose tissue [68], although the significance of this effect has not been confirmed by human data [69].”
BackgroundGlucagon in type 2 diabetes: Friend or foe?
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- Authors
- Whytock, K. L., Carnero, E. A., Vega, R. B., Tillner, J., Bock, C., Chivukula, K., Yi, F., Meyer, C., Smith, S. R., & Sparks, L. M.
- Affiliations
- AdventHealth Orlando (US)
- Translational Research Institute AdventHealth Orlando Florida USA
- Sanofi (Germany) (DE)
- Corresponding author
- Sparks, Lauren M.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2021-05-24
- Volume
- 29
- Issue
- 6
- Pages
- 1003-1013
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- OpenAlex
- W3165203237
- Cited by
- 30
- References
- 12
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 1
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucagon, energy expenditure, overweight, fat oxidation, basal metabolic rate, substrate utilization, intravenous infusion
- MeSH terms
- Adult, Calorimetry, Drug Administration Schedule, Energy Metabolism, Female, Glucagon, Humans, Infusions, Intravenous, Male, Middle Aged, Obesity, Oxidation-Reduction, Time Factors, Overweight
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