Acute GIP and GLP ‐1 Administration Exerts Differential Metabolic Effects in Totally Pancreatectomised Individuals

ABSTRACT Aims While being recognised for stimulating pancreatic insulin secretion, GIP and GLP‐1 exert various extrapancreatic effects relevant in the context of incretin‐based therapies. Here, we evaluated the extrapancreatic effects of GIP and GLP‐1, separately and combined, on postprandial physiology in totally pancreatectomised individuals. Materials and Methods In a randomised double‐blind design, 12 totally pancreatectomised individuals (five women, age: mean ± SD 58.8 ± 13.9 years; BMI: 24.7 ± 5.1 kg/m 2 ) each underwent four liquid mixed meal tests (480 kcal) during 270‐min intravenous infusions of GIP (4 pmol/kg/min), GLP‐1 (1 pmol/kg/min), GIP+GLP‐1 and saline (placebo), respectively. Blood samples, appetite‐related measures, hemodynamic measures, and ad libitum food intake data were collected. Participants continued basal insulin but omitted other medications including bolus insulin from 10 p.m. the night before. Results Compared to placebo, GLP‐1 infusion reduced postprandial glucose excursions by 45% ± 48% ( p = 0.005) and gastric emptying rate by 29% ± 36%, assessed by acetaminophen absorption ( p = 0.05), whereas the effects of GIP were similar to placebo. During GIP+GLP‐1 co‐infusion, ad libitum food intake was 31% ± 22% lower compared to placebo ( p = 0.018) but similar to GLP‐1 infusion. Compared to placebo, infusion of GIP increased heart rate by 10 ± 5.9 bpm ( p = 0.004), decreased diastolic blood pressure by 9.1 ± 5.4 bpm ( p = 0.002), and inhibited postprandial bone resorption assessed by carboxy‐terminal collagen crosslinks by 65% ± 35% ( p = 0.003), whereas GLP‐1 infusion did not affect bone resorption markers. Conclusion Physiological actions of GIP and GLP‐1 were preserved in totally pancreatectomised individuals, demonstrating independency of endogenous pancreatic factors. Trial Registration: ClinicalTrials.gov : NCT06895408