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GIP and GLP-1 Receptor Blockade in Patients Without Pancreas Reveals Hormone Functions

RPEP-154592026Krogh, Liva S L; Helsted, Mads M; Englund, Anders; Bergmann, Natasha C; Skov-Jeppesen, Kirsa; Nielsen, Casper K; Hansen, Carsten P; Rosenkilde, Mette M; Hartmann, Bolette; Holst, Jens J; Knop, Filip K; Lund, Asger B; Gasbjerg, Lærke S
evidence
The takeaway

Acute GIP and GLP-1 receptor antagonism in totally pancreatectomized patients revealed insulin-independent metabolic effects of these hormones, advancing understanding of incretin biology beyond β-cell function.

No pancreas, still works

GLP-1 has metabolic effects even when there's no pancreas to make insulin — explaining why GLP-1 drugs do much more than just lower blood sugar

What the researchers found

GIP/GLP-1 receptor antagonism in pancreatectomized patients revealed insulin-independent metabolic effects, demonstrating incretin actions beyond β-cell function.

Why it matters

Understanding what GLP-1 does WITHOUT a pancreas explains its cardiovascular, neuroprotective, and anti-inflammatory effects that don't involve insulin.

How the study worked

Acute GIP and GLP-1 receptor antagonism (infusion studies) in totally pancreatectomized patients to isolate non-pancreatic hormone effects.

What this study cannot tell us

Rare patient population. Small sample implied. Pancreatectomized patients have abnormal metabolic state.

How to read the evidence

Unique clinical antagonism study in pancreatectomized patients.

When this study was published

Published in 2025.

The bigger picture

The complete absence of pancreas provides the cleanest possible test of GLP-1's extra-pancreatic effects — a unique experimental window.

Questions still open

  • Which insulin-independent GLP-1 effects are most clinically significant?
  • Do extra-pancreatic GLP-1 effects explain cardiovascular protection?
  • Could GLP-1 drugs benefit type 1 diabetes through non-pancreatic mechanisms?

Common questions

What does GLP-1 do without a pancreas?
This study proved GLP-1 has metabolic effects independent of insulin secretion. These non-pancreatic effects likely explain why GLP-1 drugs protect the heart, brain, and kidneys.
Why study patients without a pancreas?
By removing all pancreatic effects, researchers can cleanly see what GLP-1 does elsewhere in the body — a unique experiment not possible in normal subjects.

Read the original research

Acute effects of GIP and GLP-1 receptor antagonism in totally pancreatectomized individuals: A randomized double-blind, placebo-controlled crossover study.

Diabetes, obesity & metabolism, 28(1), 275-286

View on PubMed ↗Publisher’s paper ↗

Citation

Krogh, Liva S L; Helsted, Mads M; Englund, Anders; Bergmann, Natasha C; Skov-Jeppesen, Kirsa; Nielsen, Casper K; Hansen, Carsten P; Rosenkilde, Mette M; Hartmann, Bolette; Holst, Jens J; Knop, Filip K; Lund, Asger B; Gasbjerg, Lærke S. (2026). Acute effects of GIP and GLP-1 receptor antagonism in totally pancreatectomized individuals: A randomized double-blind, placebo-controlled crossover study.. Diabetes, obesity & metabolism, 28(1), 275-286. https://doi.org/10.1111/dom.70186