GIP

also known as: Glucose-dependent Insulinotropic Polypeptide, Gastric Inhibitory Polypeptide

The 'other incretin' — the endogenous hormone that tirzepatide and retatrutide co-target alongside GLP-1, driving additive weight loss and metabolic benefits.

A 42-amino-acid incretin hormone co-equal to GLP-1 in glucose-dependent insulin secretion, whose receptor is the second target of dual-agonist drugs like tirzepatide.

Mechanism of action

Binds the GIP receptor (GIPR, a Gs-coupled GPCR) on pancreatic beta cells to stimulate glucose-dependent insulin secretion. Also acts on adipocytes (lipid storage), osteoblasts (bone formation), and centrally (appetite modulation, though the direction of effect is debated). The GIP receptor's role in weight loss vs. weight gain remains actively studied.

Primary uses

Endogenous incretin physiology
Target of tirzepatide dual agonism
Metabolic disease research
Bone metabolism research

Typical dosing

1–4 pmol/kg/min IV infusion (research only) (intravenous)

Research tool only. Therapeutic GIP activity is delivered via tirzepatide and other multi-agonists.

Regulatory status

Native GIP not approved as a therapeutic. GIP receptor is co-targeted by tirzepatide (GLP-1/GIP dual agonist, FDA-approved 2022) and retatrutide (GLP-1/GIP/glucagon triple agonist, Phase 3).

References

[review] Nauck MA, Meier JJ. "The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions." Lancet Diabetes Endocrinol, 2016;4:525-536.
[review] Campbell JE, Drucker DJ. "Pharmacology, physiology, and mechanisms of incretin hormone action." Cell Metab, 2013;17:819-837.

Related peptides

Tirzepatide

A once-weekly GLP-1/GIP dual agonist that produced unprecedented weight loss in SURMOUNT trials — up to ~21% at highest dose.

Retatrutide

An investigational triple hormone agonist that produced ~24% weight loss at 48 weeks in Phase 2 — the largest in any single-agent obesity trial to date.

Semaglutide

A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

CagriSema

Novo Nordisk's next-generation obesity injection — NDA filed December 2025, FDA review expected 2026. If approved, it would be the first GLP-1 + amylin fixed-dose combination and a direct competitive response to tirzepatide.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.