ReviewJournal of the Endocrine Society2026
Personalization of incretin therapy: can GLP-1 and GIP receptor polymorphisms influence therapy response?
Review in Journal of the Endocrine Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Incretin-based therapies-glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide and the dual GLP-1/GIP receptor agonist tirzepatide-have transformed the management of type 2 diabetes (T2D) and obesity. However, substantial interindividual variability in therapeutic response remains incompletely explained by clinical factors alone. Methods: A systematic search of PubMed, SciSpace, and Google Scholar was conducted (through May 2026) using terms including GLP1R, GIPR, polymorphisms, pharmacogenomics, semaglutide, tirzepatide, and Italian population. Relevant original studies, genome-wide association studies, and reviews were included. Results: Common GLP1R variants-notably rs6923761 (Gly168Ser) and rs10305492 (Ala316Thr)-modulate receptor expression, G-protein coupling efficiency, and downstream cAMP signaling, translating to differential HbA1c reduction and weight loss with GLP-1RAs. GIPR rs1800437 (Glu354Gln), present at ∼20% frequency in Europeans, is associated with altered incretin effect and increased nausea/vomiting risk with tirzepatide (OR 1.83). Geographic analyses reveal significant allele frequency variation between European, East Asian, and African populations; Italian-specific data remain limited but suggest frequencies consistent with broader Southern European patterns. Conclusion: Pharmacogenomic profiling of GLP1R and GIPR variants holds promise for personalizing incretin therapy. Prospective studies in Italian and broader Mediterranean cohorts are needed to define clinically actionable genotype-phenotype relationships and inform precision endocrinology practice.
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