What These Hormones Do Without a Pancreas

To find out what the gut hormones do outside the pancreas, researchers studied people who no longer have one. Twelve adults whose pancreas had been entirely removed were given drugs that block the GIP and GLP-1 receptors — and the one thing that clearly changed was bone.^[1]

Why remove the pancreas from the question

GIP and GLP-1 are called incretins because their best-known job is telling the pancreas to release insulin after a meal. But they have receptors in many other tissues, and separating those effects from the pancreatic ones is difficult in an intact person: block the hormone, insulin changes, blood sugar changes, and everything downstream of blood sugar changes with it.

People who have had a total pancreatectomy — usually for cancer or severe chronic pancreatitis — provide an unusual natural experiment. With no pancreas, there is no insulin or glucagon response to confound anything. Whatever still happens when you block a receptor has to be happening somewhere else.

Each participant did four separate 270-minute meal tests in randomized order, receiving a GIP blocker, a GLP-1 blocker, both together, or saline, without knowing which.

The bone result

Eating suppresses bone breakdown. It is a normal, well-described daily rhythm: after a meal, the markers of bone being dismantled fall, then recover. In this study the marker fell to 64% of its starting value on placebo — and only to 84% and 85% when GIP was blocked, alone or together with GLP-1.

Blocking GLP-1 alone did not do this. So the meal-driven suppression of bone breakdown is substantially a GIP effect, and it works without any pancreatic involvement at all — which is a genuinely new piece of physiology, established by a study design that could not have been run any other way.

Your own GIP is part of why eating protects your skeleton, and it does that job without asking the pancreas.

What did not change, and how to read that

Blocking either hormone had no measurable effect on glucose metabolism, gastric emptying, appetite, food intake, triglycerides or blood pressure and heart rate. The authors read this as evidence that those effects require the pancreas — take the pancreas away and blocking the hormone changes nothing, because the pathway ran through the organ that is gone.

One incidental finding is worth noting because it shows the blockers were working: when the GLP-1 receptor was blocked, circulating GLP-1 levels went up. That is the expected signature of a feedback loop being interrupted, and it is the sort of internal check that makes the rest of the results more credible.

What it means for someone taking one of these drugs

Directly, almost nothing — and the reason is the one in the warning above. The drugs activate these receptors; this study switched them off. You cannot read across.

Indirectly, it sharpens a question that does matter. Bone health during rapid weight loss is a real concern, and the fact that GIP has a direct, pancreas-independent role in the daily rhythm of bone turnover is a reason to look closely at what a GIP agonist does to bone over years. Tirzepatide is a GIP agonist. Nobody has that answer yet, and this study is one of the reasons the question is worth asking properly.

For what is known about body composition changes on these drugs, see lean mass on a drug versus dieting.