GLP-1 is not enough: can glucagon fill the energy expenditure gap? - PubMed
3 months ago
- #glucagon
- #obesity
- #energy-expenditure
- Obesity stems from an imbalance between energy intake and expenditure (EE).
- GLP-1 receptor agonists reduce weight by suppressing appetite but minimally affect EE, limiting long-term efficacy.
- Glucagon, traditionally a glucose counter-regulatory hormone, promotes lipid oxidation, substrate mobilization, and EE.
- Preclinical studies show glucagon increases oxygen consumption, stimulates brown adipose tissue, and enhances thermogenic gene programs via FGF21.
- Human studies indicate glucagon's EE effects are context-dependent, stronger in fasted or insulin-deficient states, and weaker postprandially or under hyperinsulinemia.
- GLP-1R/GCGR co-agonism shows superior weight-loss efficacy in clinical trials, advancing toward clinical use.
- Glucagon complements GLP-1 by promoting catabolism and EE, but human data remains limited and further research is needed.