Research
Hormonal
The efficacy of GIP-GLP-1 co-agonists may be explained by biased agonism and altered receptor internalization, which prevents the desensitization seen with pure GIP agonists.
The superior effect of co-agonists like tirzepatide may be due to their specific molecular design, which alters how receptors are signaled and internalized, preventing the 'shut down' (desensitization) that occurs with pure GIP agonists.
ModerateQualifiesMEDIUM confidence
It has been shown that even small changes in the GIP as well as the GLP-1 molecule may change the receptor signaling towards a preferential G protein signaling with decreased arrestin recruitment and/or reduced receptor internalization... For the GIP system, such an effect would be beneficial due to a lower degree of receptor desensitization and internalization.
Why this rating
Based on in vitro and mechanistic studies cited.
Source
GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists
Jens J. Holst et al. · The Journal of Clinical Endocrinology & Metabolism · 2020
DOI 10.1210/clinem/dgaa327
narrative_reviewCited 191×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- GIP-GLP-1 co-agonists (e.g., tirzepatide) produce superior weight loss and glycemic control compared to GLP-1 receptor agonists alone in patients with type 2 diabetes and obesity.Good
- GIP receptor antagonists can promote weight loss in non-human primates and rodents, challenging the view that GIP promotes obesity.Moderate
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