GLP-1 vs GIP vs Glucagon Receptors
The three receptors targeted by modern incretin pharmacology, side by side.
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| Receptor | Class | Main tissues | Key effects |
|---|---|---|---|
| GLP-1R | Class B GPCR | Pancreas β-cells, gut, brain, heart, kidney | Glucose-dependent insulin secretion, slowed gastric emptying, satiety |
| GIPR | Class B GPCR | β-cells, adipocytes, bone, hypothalamus | Insulin / glucagon co-stimulation, adipocyte modulation |
| GCGR | Class B GPCR | Liver, kidney, heart, adipocytes | Hepatic glucose output, lipolysis, energy expenditure |
Mono → dual → triple agonism
Mono agonists (semaglutide, liraglutide) target only GLP-1R. Dual agonists (tirzepatide) add GIPR. Triple agonists (retatrutide) add GCGR. The pharmacological rationale is that activating multiple receptors can produce complementary metabolic effects — but it also complicates the side-effect profile and the dosing.
Why dual and triple agonism is not a stack
It is worth distinguishing a polypharmacological molecule — a single agent that activates multiple receptors — from a “stack” of separate agents combined by a researcher. Tirzepatide is one molecule with dual activity, designed and tested as a single drug. Stacking separate GLP-1 and GIP agonists would be a different exercise with a different (and largely unstudied) profile.
Regulatory caution
All three agents named here are prescription-only medicines where they hold authorisation. See: POM advertising rules.