Acute <scp>GIP</scp> and <scp>GLP</scp> ‐1 Administration Exerts Differential Metabolic Effects in Totally Pancreatectomised Individuals

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: ) 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.