Pancreaticoduodenectomy alters GLP-1 and GIP responses, exploratory meta-analysis finds

BackgroundPancreaticoduodenectomy (PD) removes the duodenum and proximal jejunum, alters nutrient transit, and may modify secretion of incretin hormones involved in glucose homeostasis.ObjectiveTo 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.MethodsFollowing 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.ResultsSix 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.ConclusionsAvailable 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 registrationhttps://www.crd.york.ac.uk/prospero/, identifier 1345848.