Excessive Intrapancreatic Fat Deposition and the Potential Therapeutic Role of Glucagon-Like Peptide-1 Receptor Agonists: A Systematic Review

Excessive intrapancreatic fat deposition, also called non-alcoholic fatty pancreas disease, is marked by abnormal fat accumulation in pancreatic tissue and inked to metabolic syndrome, obesity, insulin resistance, and type 2 diabetes mellitus. Despite its clinical importance, intrapancreatic fat deposition lacks standardized diagnostic criteria and is often underdiagnosed. This systematic review explores the pathogenesis, diagnostic challenges, and clinical relevance of intrapancreatic fat deposition, with particular attention to the therapeutic potential of glucagon-like peptide-1 receptor agonists. A literature search of PubMed, Scopus, and Google Scholar, supplemented by a post-review verification search, identified six studies (two preclinical and four clinical studies) meeting pre-specified eligibility criteria for original data on a glucagon-like peptide-1 receptor agonist intervention with a pancreatic fat outcome, following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidance; several sources considered during full-text review are reclassified as secondary literature or as not evaluating a glucagon-like peptide-1 receptor agonist and are cited instead as background. Preclinical evidence indicates that liraglutide and semaglutide can attenuate pancreatic endoplasmic reticulum stress, islet-cell apoptosis, and lipid dysregulation in diet-induced obesity models. Clinical evidence is mixed: a retrospective study reported a significant reduction in pancreatic fat with liraglutide in patients with intrapancreatic fat deposition, whereas randomised trials of liraglutide, exenatide, and dulaglutide have not consistently shown a significant between-group reduction, and direct pancreatic fat outcome data for semaglutide in humans are lacking. A 2026 systematic review and meta-analysis of randomised controlled trials across glucose-lowering drug classes reported a significant pooled reduction in intrapancreatic fat deposition with glucagon-like peptide-1 receptor agonists, providing independent, quantitative support for a class effect. Glucagon-like peptide-1 receptor agonists are already established to confer benefits beyond glycaemic control and pancreatic fat, including cardiovascular, renal, and broader weight-related metabolic benefits; their potential role in intrapancreatic fat deposition is one facet of this wider profile rather than a distinct “dual-purpose” mechanism. Given small samples, heterogeneous imaging, and inability to separate pancreas-specific effects from hepatic and visceral fat reductions, evidence suggests an unconfirmed role for glucagon-like peptide-1 receptor agonists in intrapancreatic fat deposition. Prospective powered trials with standardised imaging and hepatic/visceral fat measurements are needed before clinical practice.