Changes in incretin hormone concentrations after pancreaticoduodenectomy: a systematic review and exploratory meta-analysis.

Background: Pancreaticoduodenectomy (PD) removes the duodenum and proximal jejunum, alters nutrient transit, and may modify secretion of incretin hormones involved in glucose homeostasis. Objective: To systematically review clinical evidence on postoperative changes in glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) after PD, together with co-reported hormonal and metabolic outcomes, and to perform a strictly exploratory meta-analysis where sufficiently comparable numerical data were available. Methods: Following PRISMA 2020, we reviewed human studies identified in PubMed, Embase, and Scopus from 1 January 2000 to 27 March 2026, with screening and full-text selection performed in Rayyan. Eligible studies reported GLP-1 and/or GIP after PD, after different PD reconstructions, or during post-PD nutrient-delivery interventions. Because outcome reporting was heterogeneous, quantitative pooling was restricted to exploratory random-effects syntheses of two clinically comparable post-PD reconstruction studies. Because only two studies contributed to each pooled comparison, estimates of effect size and heterogeneity were considered highly fragile and were not interpreted as confirmatory. Results: Six studies involving 134 participants met the eligibility criteria. Postprandial GLP-1 generally increased after PD or was higher in settings associated with faster gastric emptying or greater distal nutrient exposure. By contrast, GIP was reported in fewer studies than GLP-1 and showed attenuation or no consistent enhancement. Co-reported glucose, insulin, C-peptide, glucagon, PYY, and gastric-emptying measures indicated that endocrine adaptation after PD is heterogeneous and not uniformly beneficial despite the recurrent GLP-1 signal. Exploratory meta-analysis of Whipple versus pylorus-preserving PD comparisons suggested a direction favoring Whipple for early GLP-1 exposure, although confidence intervals were wide and the two-study pooled estimates were statistically fragile. Given the small number of heterogeneous studies, quantitative findings should be interpreted as exploratory. Conclusions: Available clinical evidence supports a reproducible increase in postprandial GLP-1 signaling after PD, whereas evidence for GIP is weaker, based on fewer studies, and remains sparse and inconsistent. The meta-analytic component should be regarded as exploratory and hypothesis-generating only. Larger prospective studies with standardized stimulation protocols and detailed assay reporting are needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier 1345848.