Hormonal
Glucagon receptor (GCGR) agonism increases energy expenditure and promotes weight loss, particularly when combined with GLP-1R and/or GIPR agonism in dual or triple receptor agonists.
Current obesity treatments often lead to weight regain because they don't significantly increase energy expenditure. New drugs that activate the glucagon receptor (GCGR), either alone or combined with GLP-1/GIP drugs, are designed to boost energy expenditure and prevent this metabolic slowdown. While early results show significant weight loss (up to 24% in some trials), long-term clinical data is still emerging, and these are prescription medications requiring medical supervision.
We focus our review on glucagon receptor (GCGR) agonism, which has recently been combined with both GLP-1R and GLP-1R/GIPR agonism to generate dual (e.g. survodutide, cotatutide, mazdutide, etc) and triple agonists (e.g. retatrutide, etc) for improved body weight loss via energy expenditure stimulation.
Why this rating
The paper relies heavily on preclinical rodent data and limited acute human infusion studies, noting that chronic clinical data is extremely limited.
Source
IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes
Andrew J. Elmendorf et al. · Pharmacological Research · 2025
DOI 10.1016/j.phrs.2025.108077
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