TABLE 1.

Selected GLP‐1 receptor agonists for which biased agonism is a core or intentional feature of their pharmacology

Agonist(s)	Structure	Bias	Notable physiological effects compared to “nonbiased” agonist	Reference
P5	Peptide	cAMP > β‐arrestin	↑Anti‐hyperglycaemia, ↓acute insulin, ↑[GIP]	(Zhang et al., 2015)
PX17	Peptide	Not reported, presumed to be cAMP > β‐arrestin	↑Anti‐hyperglycaemia, ↑weight loss, ↑[GIP]	(Wang et al., 2020)
Exendin‐phe1	Peptide	cAMP > β‐arrestin and GLP‐1 receptor endocytosis	↑Anti‐hyperglycaemia, ↑sustained insulin, ↓pica	(Jones, Bloom, et al., 2018)
Acylated exendin‐phe1	Peptide	cAMP > β‐arrestin	↑Anti‐hyperglycaemia, ↑weight loss	(Lucey et al., 2020)
Ex4L[Au]2 (peptide 11)	Peptide	cAMP > β‐arrestin	↑Anti‐hyperglycaemia, ↑sustained insulin	(Fremaux et al., 2019)
GLP‐1‐Val8	Peptide	cAMP > β‐arrestin	↓Acute insulin and somatostatin	(van der Velden et al., 2021)
β‐Amino acid peptidomimetics	Peptide	Varies	Not described	(Hager et al., 2016; 2017; Cary et al., 2019)
O‐GlcNAc‐modified peptides	Peptide	cAMP > β‐arrestin	↑Anti‐hyperglycaemia? a	(Levine et al., 2019)
Tirzepatide	Peptide	cAMP > β‐arrestin	↑Anti‐hyperglycaemia, ↑weight loss b	(Novikoff et al., 2021; Willard et al., 2020; Yuliantie et al., 2020)
LY3502970/OWL833	Small molecule	cAMP > β‐arrestin	Orally available c	(Kawai et al., 2020)
TT‐OAD2	Small molecule	cAMP > β‐arrestin	Orally available c	(Zhao et al., 2020)
PF‐06882961	Small molecule	cAMP > β‐arrestin (mild)	Orally available c	(Griffith et al., 2020)

^a PK differences are not accounted for.

^b GIP receptor activity may contribute.

^c No suitable “non‐biased” comparator available for physiological comparisons.