GIP — The Other Incretin

GIP (glucose‑dependent insulinotropic polypeptide) is an incretin hormone released from the upper small intestine when you eat. Like GLP‑1, it tells the pancreas, “Food incoming — get ready.” When glucose levels are high, GIP amplifies insulin secretion; when glucose is low, the signal quiets down, which makes it much safer than an always‑on insulin push.

For years GIP was the understudy in incretin research: interesting, but overshadowed by GLP‑1. That changed when drugs like tirzepatide were designed to activate both GLP‑1 and GIP receptors. In combination, the two hormones seem to produce stronger effects on blood sugar and weight than GLP‑1 alone — possibly by engaging different beta‑cell pathways and appetite circuits.

In obesity and long‑standing insulin-resistance, the body’s response to GIP can become blunted, just as with insulin itself. One idea behind dual agonists is to provide a cleaner, pharmacologic version of those signals: more precise timing, stronger receptor activation, and less of the background metabolic “static” that goes with chronic overnutrition.

GIP probably also has direct effects on fat tissue and bone, and in some contexts may even increase fat storage — biology rarely gives us simple heroes or villains. What matters clinically is how the combined GLP‑1/GIP signal behaves when you deploy it deliberately through medication.

Why It Matters

GIP’s rise from footnote to drug target shows how much nuance there is in “just hormones”: the same molecule can play very different roles in a metabolically stressed body versus a carefully designed therapy.

Closing Line

If GLP‑1 is the headline act, GIP is the talented co‑star — and when they perform together, the whole metabolic show looks different.